A Dictionary of Antibiosis 9780231876919

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A DICTIONARY OF ANTIBIOSIS

A DICTIONARY OF

ANTIBIOSIS Compiled

by LEONARD KAREL

NATIONAL INSTITUTES OF HEALTH, UNITED

STATES

PUBLIC HEALTH SERVICE, FEDERAL SECURITY AGENCY

and ELIZABETH SPENCER ROACH

NEW

YORK

1951

COLUMBIA UNIVERSITY PRESS

COPYRIGHT

1951

COLUMBIA UNIVERSITY PRESS, NEW YORK Published in Great Britain, Canada, and India by Geoffrey Cumberlege, Oxford University Press, London, Toronto, and Bombay MANUFACTURED IN THE UNITED STATES OF AMERICA

FOREWORD its inception, the Division of Research Grants and Fellowships of the National Institutes of Health has endeavored whenever possible and feasible to fulfill its prime objectives of coordination, promotion, and stimulation of research, particularly in neglected areas. It is the earnest belief of the Experimental Therapeutics Study Section that in this Dictionary of Antibiosis lies a gratifying measure of achievement of part of these objectives as related to a small but nevertheless significant facet of medical research. SINCE

It is hoped that this volume will attain the usefulness envisioned for it and that it will be a source of real assistance to those who may choose to use it. Chairman Experimental Therapeutics Study Section National Institutes of Health WALSH M C D E R M O T T ,

PREFACE of this dictionary the term antibiotic is defined as a substance derivable from living organisms and capable of adversely modifying the vital functions of specific microorganisms. The data included are arranged alphabetically and consist of ( 1 ) compilation of substances tested for antibiotic activity; ( 2 ) available information on source, extraction, chemical and physical properties, spectrum in vitro and in vivo, toxicological and pharmacological, clinical and experimental clinical results; and (3) enumeration of organisms (designated as test organisms) against which substances have been tested for antibiotic activity. Under each of the test organisms there are given, wherever applicable, the species tested against it for antibiosis, and the named antibiotics similarly tested against it or, where very long lists of substances have been tested for antibiosis and appear in one paper, the bibliographic reference only. The bibliography is arranged alphabetically, according to authors, with appropriate cross-references, and cites the complete title of each paper recorded. It has not been practicable routinely to include strain designations. For precise information regarding these designations, the bibliographic references to the individual species should be consulted. Neither has it been practicable to include two of the older antibiotics—ethyl alcohol and quinine, and only brief sketches have been given for penicillin and streptomycin, both of which have been adequately covered by other authors. F O R THE PURPOSES

L.K. E.S.R.

Bethesda, Maryland February 1, 1951

CONTENTS FOREWORD PREFACE

v vii

ABBREVIATIONS AND EXPLANATIONS

2

TEXT

3

BIBLIOGRAPHY

319

A DICTIONARY OF ANTIBIOSIS

ABBREVIATIONS AND EXPLANATIONS aS.—affinis b.p.—blood pressure cc—cubic centimeter(s) cf.—compare corr.—corrected decomp.—decomposes f.—forma gm-gram(s) higher plant—refers to seedproducing plants and to ferns hr—hour(s) i.m.—intramuscular in—inch inj (s) —injection (s) i.p.—intraperitoneal i.v.—intravenous kg—kilogram(s) 1-liter (s) lb—pound (s) LDso—median lethal dose mg—milligram (s) min—minutes

ml—milliliter (s) M.L.D.—minimum lethal dose, median lethal dose mo—month (s) mol. wt.—molecular weight m.p.—melting point M.T.D.—minimum toxic dose; maximum therapeutic dose; maximum tolerated dose n.sp. or n.spp.—new species p.o.—per os ppm—parts per million (equivalent to 1 microgram per cc) rm. temp.—room temperature s.c.—subcutaneous sp.—species (singular) spp.—species (plural) uncorr—uncorrected v. or var. -variety wk—week (s) wt.—weight yr—year(s)

Abelia floribunda, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Abelia gardneri, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Abelia schumannil, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Aberia caffra, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Abies religiosa, a higher plant, aqueous extracts of the commercial wood of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Bacillus anthracis. See Sanchez et al., 1948. Abrus precatorius, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. abscesses, clinical, see BACITRACIN; GRAMICIDIN S;

PENICILLIN;

STREPTOMYCIN;

TYROTHRICIN.

Absklia glauca, a fungus, the culture media of which are ineffective in vitro against .Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1943a. Absidia orchidis, a fungus which gives doubtful results when tested in vitro against Escherichia coli and Staphylococcus aureus. See Robbins et al., 1945. Absidia ramosa, a fungus which gives doubtful results when tested in vitro against Escherichia coli and Staphylococcus aureus. See Robbins et. al., 1945. Abutilon "boule de neige," a higher plant, aqueous extracts of the garden hybrid of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Abutilon striatum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Abutilon thompsonii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Acacia jurema, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Acacia podalyriaefolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Acacia verticillata, a higher plant, aqueous extracts of which are ineffective i/i vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Acaena adscandens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Acaena myriophylia, a higher plant, aqueous ex;racts of which are ineffective in vitro against

Staphylococcus aureus and Escherichia coll. See Osborn, 1943. Acalypha canrana, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Acalypha hamiltoniana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Acalypha hlsplda, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Acalypha macrostachya, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Acalypha montevhliensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Acalypha virginica, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Acalypha wilkesiana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Acalypha wilkesiana v. macafrana, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Acantholimon gtomaceum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Acanthopanax simonii, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Acanthopyros sp., a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Acanthorhynchus vaccinlL 1 See ACTINOMYCES A N N U L A T U S ; A C T I N O M Y C E S FLAVOVIRENS; A C T I N O M Y C E S GOUGEROTI; A C T I N O M Y C E S HALSTEDII; A C T I N O M Y C E S MADURAE; A C T I N O M Y C E S VIRIDO-

CHROMOGENUS. 2 As test organism in vitro, see Alexopoulos and Herrick, 1942 (actinomycetes). Acanthospermum xanthoides, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Acanthus montanns, a higher plant, aqueous extracts of which are ineffective in vitro against Siaphvlococcus aureus and Escherichia coli. See Osborn, 1943. Acanthus niger, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. St« Osborn, 1943. Acer negundo, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945.

Cross references are indicated by SMALL CAPITALS

ACER PLANTANOIDES

[4]

Acer plantanoides, a tree, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis [1], Extracts of the litter from this tree inhibit Staph, aureus [2], See [1] Gottshall et al., 1949; [2] Melin and Wiken, 1946. Accr psendo-platanus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Acerates viridiflora, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Acetabula vulgaris, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Wilkins, 1946a. Acetobacter spp., see K O J I C ACID. Achillea agerattfolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Achillea clypeolata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Achillea filipendulina, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Achillea grandiflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Achillea impatiens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Achillea magna, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Achillea millefolium, a higher plant, ether extracts of the flower and leaf of which are effective in vitro against Staphylococcus aureus, while aqueous extracts of the flower and leaf and aqueous and ether extracts of the stem are ineffective. Only aqueous extracts of the flower and aqueous and ether extracts of the leaf inhibit the spores of Neurospora crassa. None of these extracts is effective against Escherichia coli [1]. Aqueous extracts of this plant are also reported to be ineffective against Staph, aureus and E. coli [2], Extracts of the tops of the plant are found to be slightly effective in the treatment of experimental malaria [3]. In another series of tests in vitro aqueous extracts showed little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumejaciens [4]. See [1J Schnell and Thayer, 1949; [2J Osborn, 1943; [3] Spencer et al., 1947; [4] Hayes, 1947. Achillea ptarmica, a higher plant, aqueous extracts of the flower and stem of which are effective in vitro against Escherichia coli, while aqueous extracts of the leaf and root are ineffective. None of these extracts inhibits Staphylococcus aureus or the spores of Neurospora crassa [1], Aqueous extracts of this plant are also reported to be ineffective against Staph, aureus and F. coli [2]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943.

Achillea serbica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Achimenes haageana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Osborn, 1943. Achimenes rosea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coll. See Osborn, 1943. Achorion gallinae, as test organism in vitro, see ASPERGILLIC ACID; C H E 1 R 0 L 1 N E ; CLAVACIN; F U M I O ACIN; G U O T O X I N ; M Y C O P H E N O L I C CILLIN; PROACTINOMYCIN.

ACID;

PENI-

Achorion gypseum, as test organism in vitro, s e e ASPERGILLIC ACID; C H E I R O L I N E ; CLAVACIN; FUMIGACIN; GLIOTOXIN; L Y C O P E R S I C U M PIMPIN E L L I F O L I U M ; M Y C O P H E N O L I C ACID; P E N I C I L L I C ACID; P E N I C I L L I N ; P R O A C T I N O M Y C I N ; S O L A N I N E .

Achorion quinckeanum, as test organism in vi-

tro, s e e ASPERGILLIC ACID; C H E I R O L I N E ; CLAVACIN; FUMIGACIN; GLIOTOXIN; MYCOPHENOLIC ACID; P E N I C I L L I C ACID; P E N I C I L L I N ; P R O A C T I N O MYCIN.

Achorion schoenleinii, a fungus which causes little or no inhibition in vitro of Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. As test organism in vitro, see LYCOPERSICUM PIMPINELLIFOLIUM; TILIN; SOLANINE.

MYCOSUB-

Achorion violuceum, as test organism in vitro, s e c ASPERGILLIC ACID; C H E I R O L I N E ; CLAVACIN; FUMIGACIN; GLIOTOXIN; MYCOPHENOLIC ACID; PENICILLIN; PROACTINOMYCIN.

Achras sapota, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1|. Other extracts are ineffective against Staph, aureus, E. coli, and Proteus X-19 [2], See [1] Osborn, 1943; [2] Cardoso and Santos, 1948. Achromobacter sp., a microorganism effective in vitro against Fusarium and Sclerotinia. See Chudiakov, 1935. Achromobacter spp., as test organisms in vitro, see A N T I B I O T I C EI.-,. Achromobacter lacticom, as test organism in vitro, see L E P T O T A E N I A DISSECTA; R H U S H I R T A . Achromobacter stutzeri, as test organism in vitro,

see

ACT1NOMYCIN.

Achyrocline flaccida, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Achyrocline satureioides, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Acia stenodon, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Acia uda, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus. Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Acladium sp., as test organism in vitro, see ANTIBIOTIC

EI.-.

Acmadenia frankliniae. a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli See Osborn, 1943.

Cross references are indicated by

SMALL CAPITALS

ACTIDIONE

[5] Aconitum cammamm, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococci/', aureus and Escherichia coli. See Osborn, 1943. Aconitum variegatum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aconitum vulparia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Acorns calamus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro aqueous extracts showed little or no inhibition against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2], See [1] Osborn, 1943; [2] Hayes, 1947. Acrostalagmus cinnabarinus, as test organism in vitro, see P E Z I Z A SCLEROTIORUM. actidione, a crystalline antibiotic obtained from culture filtrates of Streptomyces griseus by chloroform extraction [1], or from its mycelia by acetone or ether extraction [2]. It is soluble in chloroform, ether, water, acetone, ethanol, and amyl acetate [1, 2, 3, 4] and is inactivated at rm. temp, by acetic anhydride, sodium acetate, and dilute alkali [3,4]. It is thermostabile [ 11. The crystals are colorless plates, the m.p. is 115 "-116.5 ; the empirical formula is CisHsriNOi; and the proposed structural formula [5, 12) is as follows: =o

CHs— X

CHOH —

CH2

NH

*o SPECTRUM — Actidione inhibits the following in vitro in concentrations of 1 mg/cc or less: Asporomyces urae [6] Blastomyces dermatitidis [61 Cryptococcus neoformans [3] Debaryomyces globosum [6j Hansenuta anomala [61 Hansenula apiculata [6] Hormodendrum pedrosoi [1] Monosporium apiospermum [7] Nematospora phaseoli ! 6; Phialophora verrucosa [7] Picliia membranaefaciens [61 Powdery mildew [8 ] Rhodotorula glutinis [6] Rhodotorula sp. [ l j Saccharomyces carlsbergensis [6] Saccharomyces cerevisiae | 6 ^ Saccharomyces ellipsoideus v. burgundy [6] Saccharomyces jragilis [6! Saccharomyces pastorianus Ui] Schizosaccharnmyces ponihe \ 6! Schwanniomyces occidentalis ' 6 ' Sporobolomyces salmonicolor ' 6 , Torula Wilis \ 6 ; Torulaspora fermentati [61 Waksman, Schatz, and Reilly [2] found the following to be inhibited in vitro (figures in parentheses denote inhibition units gm of actidione): Bacillus mvcoides (320,000), Ii. subtilis (800,000), Mycobacterium avium (11,000), and Myco, plilei (210,000).

The following results were obtained with 50 micrograms cc in tests against various spp. of Trichomonas after 48 hr incubation [9].: No. of organisms/mm' T. foetus T. gallinae T. vaginalis Control 5,140 1,460 1,600 Actidione 1,490 0 10 The following organisms are unaffected in vitro by 1 mg/cc [6]: Aerobacter aerogenes Bacillus mycoides Bacillus subtilis Candida albicans Coccidioides immitis Endomyces magnusii Escherichia coli (ieotrichum sp. Hormodendrum compaclum Kloeckera apiculata Mycotorula roseo-corrallina t^ o cardio asteroides Phytomonas campestris Pityrosporum ovale Proteus vulgaris Pseudomonas aeruginosa Saccharomyces ¡actis Salmonella schottmuelleri Sporotrichum schenckii Staphylococcus aureus Streptococcus fecalis Streptococcus pyogenes Trichophyton mentagrophytes Trichophyton rubrum There are fewer than 3,200 growth-inhibition units/gm of actidione for Mycobacterium tuberculosis hominis [2], The activity of actidione is unaffected by the presence of whole blood or serum, but its assay is considerably affected by the size of the inoculum of the test organism, Saccharomyces pastorianus [6]. Susceptible strains of yeasts readily develop resistance to actidione [7], A series of in vitro tests with actidione in concentrations varying from 0.001 mg to 0.008 mg/cc against Cryptococcus neoformans resulted in killing the various strains used [11], TOXICITY.—The L D G O in rats is 2.7 mg/kg s.c. or 2.5 mg/kg i.V.; in cats, 4 mg/kg ¡.p.; in rabbits, 17 mg/kg i.V.; in guinea pigs, 60 mg/kg s.c. [4, 6]; in mice, 150 mg/kg i.v. [3, 4, 6]. Actidione killed mice given 2 mg/day (100 to 150 m g / k g ) in 5 days, and mice given 1 mg/day (50 to 75 m g / k g ) in 8 to 12 days, but it was tolerated without signs of toxicity when administered in doses of 0.1 and 0.2 nig-'day [11], A BSORPTION. — Actidione is rapidly absorbed after i.p. inj in rat, dog, and guinea pig, and is demonstrable in the plasma for at least 90 min [10]. EXPERIMENTAL CLINICAL RESULTS. —When administered to mice which have had inoculations of 90,000 organisms of one of the strains of Cryptococcus neoformans, actidione was without demonstrable effect when given in doses of 1 mg i.m. or s.c. to 4 mice, and in doses of 0.2 mg to 4 additional mice. Against another strain of cryptococcus administered to mice i.v. in an inoculation of 660,000 organisms, actidione likewise had no effect. In this instance 5 mice were put on a dosage schedule of 0.2 mg/day i.m. and i.v. and an

Cross references are indicated by SMALL CAPITALS

ACTINIDIA ARGUTA

[6]

additional S mice were given 1 mg/day. Treatment consisted of inj of the drug twice a day for 5 days and once a day for 14 days. The animal» on larger doses of the drug apparently experienced cumulative toxic effects since they were sicker than the controls. In man, actidione was used in only one patient and proved ineffective. Cultures of the spinal fluid, however, showed marked reduction in the number of cryptococci present in the fluid itself. This suggests an in vitro fungicidal effect providing the drug can be brought into direct contact with the infecting agent, especially since it was found that serum does not inactivate the drug [11]. See [1] Whiffen et al., 1946 [2] Waksman, Schatz, and Reilly, 1946; [3] Leach et al., 1947; [4] Leach and Ford, 1948; [5] Kornfeld and Jones, 1948; [6] Whiffen, 1948; [7] Whiffen, 1947a; [8] Tukey, 1948; [9] Waksman, Harris, Kupferberg, Singher, and Styles, 1949; [10] Goth and Robinson, 1949a; [11] Fisher, 1950; [12] Carter and Ford. 1950. Actinidia areata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Actinidia HiHimfit, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Actin obacilhis lignieresL, as test organism in Vitro,

SEE LICHENIFORMIN.

Acttatococcns cyaneus-antibloticus, see

LITMO-

CIDIN.

Actinomeris squarrosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. actinomlceUna, an antibiotic produced by an organism of the Actinomyces group. It is heat resistant and is highly inhibitory for some gram-positive bacilli and less active against gram-negative bacilli. See "A New Antibiotic" (actinomicelina), 1948. Actinomyces, see also STREPTOMYCES. Actinomyces sp., an actinomycete which in vitro inhibits the growth of Ophiobolus graminis. See Broadfoot, 1933a and b. Actinomyces

spp.

1 S e e ACTINOMYCETIN;

SMEGMATIS FACTOR. 2 vitro,

see

NISIN;

As

SUBTILIN;

test

ANTI-

organisms

in

COLLETOTRICHUM

GLOEOSPORIOIDES.

A c t i n o m y c e s A - 1 0 , see LAVENDULIN.

Actinomyces A-105, see ACTINORUBIN. Actinomyces albicans, an actinomycete which is effective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces alboflavns, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces albosporeos, see ACTINORUBIN. Actinomyces albas, a microorganism which inhibits in vitro the growth of these fungi [1]: Anthostomella sp. Botrytis tulipae Cephalothecium roseum Colletotrichum lindemuthianum Gloeosporium affine Gloeosporium musarum Physalospora cydoniae Volutella fructi Zygorhynchus moelleri It is ineffective in vitro against Mycococcus ruber [2], See [1] Alexopoulos et al., 1938;

[2] Krassilnikov and Koreniako, 1939. See also ACTINOMYCETIN. As test organism in vitro, see STREPTOTHRICIN.

Actinomyces annnlatns, an actinomycete which in vitro strongly inhibits Acanthorhynchus vaccinii, Sclerotinia sclerotiorum, Glomerella cingulata, and Botrytis cinerea; inhibits Phycomyces blakesleeanus, Phoma betae, and Alternaria solani; and weakly inhibits Fomes fraxinophilus. It is ineffective against Stereum gausapatum. See Alexopoulos and Herrick, 1942. Actinomyces antibióticos, see ACTINOMYCIN. Actinomyces aromatkrus, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces asteroides, as test organism in vitro,

s e e BACILLUS SP., SUBTILIN.

Actinomyces aurantiacus, an actinomycete which is effective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. As test o r g a n i s m in vitro,

see AZOTOBACTER CHROOCOC-

C U M ; AZOTOBACTER VINELANDII; BACILLUS MEGATHERIUM; BACILLUS MESENTERICUS; BACILLUS MYCO ID ES; BACILLUS PRODIGIOSUS; BACILLUS PYOCYANEUS; BACILLUS SUBTILIS; BACILLUS T U MESCENS; BACTERIUM CLOVER; BACTERIUM KIDNEY BEAN; BACTERIUM LUCERNE; BACTERIUM LUPIN; BACTERIUM MELILOT; BACTERIUM PEA; BACTERIUM RADICICOLA; BACTERIUM SOY; BACTERIUM VETCH; BUTTER BACILLUS; CORYNEBACTERIUM; ESCHERICHIA COLI; MICROCOCCUS CANDICANS; MICROCOCCUS CITREUS; MICROCOCCUS FLAVUS; MICROCOCCUS L U T E U S ; MICROCOCCUS LYSODEIKTICUS; MICROCOCCUS ROSEUS; M I C R O COCCUS RUBER; MIST BACILLUS; MYCOBACTERIUM; MYCOBACTERIUM ALBUM; MYCOBACTERIUM BIFIDUM; MYCOBACTERIUM BREVICALE; MYCOBACTERIUM CITREUM; MYCOBACTERIUM CYANEUM; M Y C O B A C T E R I U M DIASTATICUM; MYCOBACTERIUM F I L I F O R M E ; MYCOBACTERIUM FLAVUM; MYCOBACTERIUM GLOBIFORME; M Y C O BACTERIUM GROSSBERGER; MYCOBACTERIUM HYALINIUM; MYCOBACTERIUM L U T E U M ; M Y C O BACTERIUM M U C O S U M ; MYCOBACTERIUM N I G R U M ; MYCOBACTERIUM PHLEI; M Y C O B A C T E R I U M RABINOWITSCH; MYCOBACTERIUM R U B R U M ; M Y C O BACTERIUM SMEGMA; MYCOBACTERIUM TOBLER; MYCOBACTERIUM TUBERCULOSIS; M Y C O C O C C U S ALBUS; MYCOCOCCUS CAPSULATUS; M Y C O C O C C U S CITREUS; MYCOCOCCUS LACTIS; MYCOCOCCUS LUTEUS; MYCOCOCCUS MUCOSUS; M Y C O C O C C U S RUBER; MYCOCOCCUS TETRAGENUS; PROACTINOMYCES ALBUS; PROACTINOMYCES CHROMOGENUS; PROACTINOMYCES CITREUS; PROACTINOMYCES CORALLINUS; PROACTINOMYCES DIASTATIcus; PROACTINOMYCES FLAVUS; PROACTINOMYCES LACTIS; PROACTINOMYCES RUBER; P R O ACTINOMYCES VIRIDIS; PROTEUS VULGARIS; PROTEUS ZENKERI; PSEUDOMONAS FLUORESCENS; RADIOBACTER; SARCINA FLAVA; SARCINA LUTEA; SARCINA RUBRA; STAPHYLOCOCCUS AUREUS.

Actinomyces aureus, an actinomycete which is effective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces bovis, as test organism in vitro, see

PENICILLIN.

Actinomyces californicus, see ACTINORUBIN. Actinomyces cellulosae, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces coelicolor, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939.

C r o s s r e f e r e n c e s a r e i n d i c a t e d b y SMALL CAPITALS

[7] Actinomyces cyancas, an a c t i n o m y c e t e which is e f f e c t i v e in vitro against Mycococcus ruber. See K r a s s i l n i k o v and K o r e n i a k o , 1939. A c t i n o m y c e s cylindrosporus, an a c t i n o m y c e t e w h i c h is i n e f f e c t i v e in vitro against Mycococcus ruber. See K r a s s i l n i k o v and K o r e n i a k o , 1939.

Actinomyces cylindrosporus virldans, an actin o m y c e t e w h i c h is ineffective in vitro against Mycococcus ruber. See Krassilnikov and K o r e n i a k o , 1939. A c t i n o m y c e s erythrens, see ACTINORUBIN. A c t i n o m y c e s e r y t h r o c h r o m o g e n u s , an a c t i n o m y cete w h i c h is e f f e c t i v e in vitro against Mycococcus ruber. See K r a s s i l n i k o v and K o r e n i a k o , 1939. A c t i n o m y c e s farinosus, an a c t i n o m y c e t e w h i c h is i n e f f e c t i v e in vitro against Mycococcus ruber. See K r a s s i l n i k o v and K o r e n i a k o , 1939. A c t i n o m y c e s flavovirens, an actinomycete w h i c h in vitro inhibits Acanthorhynchus vaccinii and w e a k l y i n h i b i t s Phycomyces blakesleeanus, Sclerotinia sclerotiorum, Glomerella cingulata, Phoma betae, Botrytis cinerea, Alternaria solani, Stereum gausapatum, and Fomes fraxinophilus. See A l e x o p o u l o s and H e r r i c k , 1942. A c t i n o m y c e s flavoviridis, an a c t i n o m y c e t e w h i c h is i n e f f e c t i v e in vitro against Mycococcus ruber. See K r a s s i l n i k o v and K o r e n i a k o , 1939. A c t i n o m y c e s flavus, an actinomycete w h i c h is i n e f f e c t i v e in vitro against Mycococcus ruber. See K r a s s i l n i k o v and K o r e n i a k o , 1939. A c t i n o m y c e s fosciculus, an actinomycete w h i c h is e f f e c t i v e in vitro against Mycococcus ruber. See K r a s s i l n i k o v and K o r e n i a k o , 1939. A c t i n o m y c e s f r a d i i . 1 See ACTINORUBIN. 2 A s test o r g a n i s m in vitro, see QUERCETIN. A c t i n o m y c e s f u m o s u s n. sp., an a n t i n o m y c e t e w h i c h is e f f e c t i v e in vitro against Mycococcus ruber. See K r a s s i l n i k o v and K o r e n i a k o , 1939. A c t i n o m y c e s fuscus, an actinomycete w h i c h is i n e f f e c t i v e in vitro against Mycococcus ruber. See K r a s s i l n i k o v and K o r e n i a k o , 1939. A c t i n o m y c e s glaucus, an a c t i n o m y c e t e w h i c h is e f f e c t i v e in vitro against Mycococcus ruber. See K r a s s i l n i k o v and K o r e n i a k o , 1939. A c t i n o m y c e s globlsportis, an actinomycete w h i c h is i n e f f e c t i v e in vitro against Mycococcus ruber. See K r a s s i l n i k o v and K o r e n i a k o , 1939. A s test o r g a n i s m in vitro, see AZOTOBACTER CHROOCOCCUM; AZOTOBACTER VINELANDU; BACILLUS MEGATHERIUM; BACILLUS MESENTERICUS; BACILLUS MYCOIDES; BACILLUS PRODIGIOSUS; BACILLUS PYOCYANEUS; B A C I L L U S SUBTILIS; BACILLUS TUMESCENS; BACTERIUM CLOVER; BACTERIUM KIDNEY BEAN; BACTERIUM LUCERNE; BACTERIUM LUPIN; BACTERIUM MELILOT; BACTERIUM PEA; BACTERIUM RADICICOLA; BACTERIUM SOY; BACTERIUM VETCH; BUTTER BACILLUS; CORYNEBACTERIUM; ESCHERICHIA COLI; MICROCOCCUS CANDICANS; MICROCOCCUS CITREUS; MICROCOCCUS FLAVUS; MICROCOCCUS LUTEUS; MICROCOCCUS LYSODEIKT1CUS; M I C R O C O C C U S ROSEUS; MICROCOCCUS RUBER; MIST BACILLUS; M Y C O BACTERIUM; MYCOBACTERIUM ALBUM; MYCOBACTERIUM BIFIDUM; MYCOBACTERIUM BREVICALE; MYCOBACTERIUM CITREUM; MYCOBACTERIUM CYANEUM; MYCOBACTERIUM DIASTATICUM; M Y COBACTERIUM FILIFORME; M Y C O B A C T E R I U M FLAVUM; MYCOBACTERIUM GLOBIFORME; M Y C O BACTERIUM G R O S S B E R G E R ; MYCOBACTERIUM HYALINUM; MYCOBACTERIUM LUTEUM; MYCOBACTERIUM MUCOSUM; MYCOBACTERIUM NIGRUM; MYCOBACTERIUM PHLEI; MYCOBACTERIUM

ACTINOMYCES

HALSTEDD

RABINOWITSCH; M Y C O B A C T E R I U M RUBRUM; MYCOBACTERIUM S M E G M A ; MYCOBACTERIUM TOBLER; MYCOBACTERIUM TUBERCULOSIS; M Y C O COCCUS ALBUS; M Y C O C O C C U S CAPSULATUS; MYCOCOCCUS CITREUS; MYCOCOCCUS LACTIS; MYCOCOCCUS LUTEUS; MYCOCOCCUS MUCOSUS; MYCOCOCCUS RUBER; MYCOCOCCUS TETRAGENUS; P R O A C T I N O M Y C E S ALBUS; PROACTINOMYCES CHROMOGENUS; PROACTINOMYCES CITREUS; PROACTINOMYCES CORALLINUS; PROACTINOMYCES DIASTATICUS; PROACTINOMYCES FLAVUS; PROACTINOMYCES LACTIS; PROACTINOMYCES RUBER; PROACTINOMYCES VIRIDIS; PROTEUS VULGARIS; PROTEUS ZENKERI; PSEUDOMONAS FLUORESCENS; RADIOBACTER; SARCINA FLAVA; SARCINA LUTEA; SARCINA RUBRA; STAPHYLOCOCCUS AUREUS. A c t i n o m y c e s g o o g e r o t i , an a c t i n o m y c e t e w h i c h in vitro strongly inhibits Phycomyces blakesleeanus, Acanthorhynchus vaccinii, Sclerotinia sclerotiorum; Glomerella cingulata, Phoma betae, Botrytis cinerea, Alternaria solani, Stereum gausapatum, a n d Fomes fraxinophilus, See A l e x o p o u l o s and H e r r i c k , 1942. A c t i n o m y c e s gnuninis, as test o r g a n i s m in vitro, see POLYPEPTIN. A c t i n o m y c e s griseus, an a c t i n o m y c e t e w h i c h is e f f e c t i v e in vitro against Mycococcus ruber. See K r a s s i l n i k o v a n d K o r e n i a k o , 1939. As test o r g a n i s m in vitro, see AZOTOBACTER CHROOCOCCUM; AZOTOBACTER VINELANDU; BACILLUS MEGATHERIUM; BACILLUS MESENTERICUS; BACILLUS MYCOIDES; BACILLUS PRODIGIOSUS; BACILLUS PYOCYANEUS; BACILLUS SUBTILIS; BACILLUS TUMESCENS; BACTERIUM CLOVER; BACTERIUM KIDNEY BEAN; BACTERIUM LUCERNE; BACTERIUM LUPIN; BACTERIUM MELILOT; BACTERIUM PEA; BACTERIUM RADICICOLA; BACTERIUM SOY; BACTERIUM VETCH; BUTTER BACILLUS; CORYNEBACTERIUM; E S C H E R I C H I A COLI; MICROCOCCUS CANDICANS; MICROCCOCUS CITREUS; MICROCOCCUS FLAVUS; MICROCOCCUS GRISEUS; MICROCOCCUS LUTEUS; MICROCOCCUS LYSODEDCTICUS; MICROCOCCUS RUBER; MIST BACILLUS; M Y C O BACTERIUM; MYCOBACTERIUM ALBUM; M Y C O BACTERIUM BIFIDUM; MYCOBACTERIUM BREVICALE; MYCOBACTERIUM CITREUM; M Y C O BACTERIUM CYANEUM; MYCOBACTERIUM DIASTATICUM; MYCOBACTERIUM FILIFORME; MYCOBACTERIUM FLAVUM; MYCOBACTERIUM GLOBIFORME; MYCOBACTERIUM GROSSBERGER; MYCOBACTERIUM HYALINUM; MYCOBACTERIUM LUTEUM; M Y C O BACTERIUM MUCOSUM; MYCOBACTERIUM NIGRUM; MYCOBACTERIUM PHLEI; MYCOBACTERIUM RABINOWITSCH; M Y C O B A C T E R I U M RUBRUM; MYCOBACTERIUM S M E G M A ; MYCOBACTERIUM TOBLER; MYCOBACTERIUM TUBERCULOSIS; M Y COCOCCUS ALBUS; MYCOCOCCUS CAPSULATUS; MYCOCOCCUS CITREUS; MYCOCOCCUS LACTIS; MYCOCOCCUS LUTEUS; MYCOCOCCUS MUCOSUS; MYCOCOCCUS RUBER; MYCOCOCCUS TETRAGENUS; PROACTINOMYCES ALBUS; PROACTINOMYCES CHROMOGENES; PROACTINOMYCES CITREUS; PROACTINOMYCES CORALLINUS; PROACTINOMYCES D I A S T A T I C U S ; PROACTINOMYCES FLAVUS; PROACTINOMYCES LACTIS; PROACTINOMYCES RUBER; PROACTINOMYCES VIRIDIS; PROTEUS VULGARIS; PROTEUS ZENKERI; PSEUDOMONAS FLUORESCENS; RADIOBACTER; SARCINA FLAVA; SARCINA LUTEA; SARCINA RUBRA; STAPHYLOCOCCUS AUREUS. A c t i n o m y c e s haistedii, an a c t i n o m y c e t e w h i c h in vitro strongly inhibits Acanthorhynchus vaccinii and Fomes fraxinophilus; inhibits Botrytis cinerea and Stereum gausapatum; and w e a k l y inhibits Sclerotinia sclerotiorum, Glomerella

Cross references are indicated by SMALL CAPITALS

ACTINOMYCES

ISRAELI

[8]

cingulata, and Phoma betae. It does not inhibit Phycomyces blakesleeanus or Alternaria solani. See Alexopoulos and Herrick, 1942. Actinomyces Israeli, as test organism in vitro, see

BACITRACIN.

see

STREPTOTHRICIN.

Actinomyces lactis, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces lavendulae. 1 See LAVENDULIN; STREPTOTHRICIN. 2 As test organism in vitro, Actinomyces longlsporus albus, an actinomycete which is effective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces longbpoius ruber, an actinomycete which is effective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces madurae, an antinomycete which in vitro strongly inhibits Acanthorhynchus vaccinii, Sclerotinia sclerotiorum, Glomerella cingulata, Phoma betae, Botrytis cinerea, Alternaria solani, Fomes fraxinophilus, and Colletotrichum gloeosporioides. It inhibits Phycomyces blakesleeanus and weakly inhibits Stereum gausapatum. See Alexopoulos and Herrick, 1942. Actinomyces marinoUmosus, a marine actinomycete which is effective in vitro against Bacillus megatherium, Bacillus mycoides, Micrococcus roseus, and Sarcina lutea, and ineffective against Bacillus anthracis, Bacillus subtilis, Corynebacterium pseudodiphthericum, Mycobacterium lacticola, Proteus vulgaris, Salmonella typhimurium, Shigella paradysenteriae, Staphylococcus aureus, Staph, citreus, and Streptococcus fecalis. The medium in which this organism is cultured is also active after passage through a Seitz or Mandler filter. See Rosenfeld and ZoBell, 1947. Actinomyces melanocyclus, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces niger, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces odoratus, an actinomycete which is effective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces pelletieri, as test organism in vitro, s e e SUBTILIN.

Actinomyces roseolas, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces roseus, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. See a l s o SULF ACTIN.

Actinomyces ruber, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces scabies, as test organism in vitro, s e e ASPERGILLIC ACID; BERBERINE; BURDOCK; CHEIROLINE; CLAVACIN; GLIOTOXIN; MYCOPHENOLIC ACID; PENICILLIC ACID; PROACTINOMYCIN; SPIRAEA; TYROTHRICIN.

Actinomyces sulphureus, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces verne, an actinomycete which is effective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces verticillatus, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939.

Actinomyces violáceos, an actinomycete which is effective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. See also MYCETIN. As test organism in vitro, see AZOTOBACTER C H R O O C C O C U M ; AZOTOBACTER VINELANDII; BACILLUS MEGATHERIUM; BACILLUS MESENTERICUS; BACILLUS MYCOIDES; BACILLUS PRODIGIOSUS; BACILLUS PYOCYANEUS; BACILLUS SUBTILIS; BACILLUS TUMESCENS; BACTERIUM CLOVER; BACTERIUM KIDNEY BEAN; BACTERIUM LUCERNE; BACTERIUM L U P I N ; BACTERIUM M E L I LOT; BACTERIUM PEA; BACTERIUM RADICICOLA; BACTERIUM SOY; BACTERIUM VETCH; BUTTER BACILLUS; CORYNEBACTERIUM; ESCHERICHIA COLI; MICROCOCCUS CANDICANS; MICROCOCCUS CITREUS; MICROCOCCUS FLAVUS; MICROCOCCUS . L U T E U S ; MICROCOCCUS LYSODEIKTICUS; M I C R O COCCUS ROSEUS; MICROCOCCUS RUBER; MIST BACILLUS; MYCOBACTERIUM; MYCOBACTERIUM ALB U M ; MYCOBACTERIUM BIFIDUM; MYCOBACTERIU M BREVICALE; MYCOBACTERIUM CITTIEUM; M Y COBACTERIUM CYANEUM; MYCOBACTERIUM DIASTATICUM; MYCOBACTERIUM FILIFORME; M Y C O BACTERIUM FLAVUM; MYCOBACTERIUM GLOBIFORM E ; MYCOBACTERIUM GROSSBERGER; MYCOBACT E R I U M HYALINUM; MYCOBACTERIUM L U T E U M ; MYCOBACTERIUM M U C O S U M ; MYCOBACTERIUM N I G R U M ; MYCOBACTERIUM PHLEI; MYCOBACTERIUM RABINOWITSCH; MYCOBACTERIUM RUB R U M ; MYCOBACTERIUM SMEGMA; MYCOBACTER I U M TOBLER; MYCOBACTERIUM TUBERCULOSIS; MYCOCOCCUS ALBUS; MYCOCOCCUS CAPSULATUS; MYCOCOCCUS CITREUS; MYCOCOCCUS LACTIS; MYCOCOCCUS LUTEUS; MYCOCOCCUS MUCOSUS; MYCOCOCCUS RUBER; MYCOCOCCUS TETRAGEN U S ; PROACTINOMYCES ALBUS; PROACTINOMYCES CHROMOGENUS; PROACTINOMYCES CITREUS; P R O ACTINOMYCES CORALLINUS; PROACTINOMYCES DIASTATICUS; PROACTINOMYCES FLAVUS; PROACT I N O M Y C E S LACTIS; PROACTINOMYCES RUBER; PROACTINOMYCES VIRIDIS; P R O T E U S VULGARIS; P R O T E U S ZENKERI; PSEUDOMONAS FLUORESCENS; RADIOBACTER; SARCINA FLAVA; SARCINA LUTEA; SARCINA RUBRA; STAPHYLOCOCCUS AUREUS.

Actinomyces violaceus niger, an actinomycete which is effective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces violaceus ruber, as test organism in vitro,

see STREPTOTHRICIN.

Actinomyces viridis, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces viridis sterUls, an actinomycete which is ineffective in vitro against Mycococcus ruber. See Krassilnikov and Koreniako, 1939. Actinomyces virldochromogenus, an actinomycete which in vitro inhibits Glomerella cingulata, Phoma betae, Alternaria solani, Stereum gausapatum, and Fomes fraxinophilus, but does not inhibit Phycomyces blakesleeanus, Acanthorhynchus vaccinii, Sclerotinia sclerotiorum, or Botrytis cinerea [ l j . It is reported to be ineffective in vitro against Mycococcus ruber [2], See [1] Alexopoulos a n d [2] Krassilnikov and Koreniako, 1939. actinomycete, Meredith's, see MUSARIN. actinomycetes, as test organisms in vitro, see COLLETOTRICHUM

GLOEOSPORIOIDES.

actinomycetin, a bacteriolytic substance extracted f r o m the culture filtrates of Actinomyces albus [1] and several other A. spp. [2]. It is probably a polypeptide enzyme. Actinomycetin lyses dead bacteria, while the producing organism is effective against some living gram-positive bacteria. It is soluble in

C r o s s references are indicated by SMALL CAPITALS

ACTINORUBIN

[9] water, insoluble in ether and ethanol, and is precipitated by acetone, ethanol, and ammonium sulphate [ 11. The activity is thermolabile, 60'-70°C. being sufficient to destroy it [2). Actinomycetin is nontoxic or very slightly toxic t o experimental animals [ 1 ]. See [ 1 ] Waksman, 1945; [2] Hoogerheide, 1944. actinomycin, a crystalline antibiotic isolated f r o m the culture filtrates of Actinomyces (Streptomyces) antibioticus [1J and other Streptomyces spp. [ 2 , 3 , 4 ] . It was formerly thought [1J that the activity occurred in two fractions, A and B, having different antimicrobial actions; investigators now believe that the activity of the so-called "actinomycin B" is due to contamination with the A fraction [3], T h e antibiotic is extracted f r o m the filtrates with ethyl ether, petroleum ether, ethanol, and chloroform [5J, and purified by chromatographic adsorption and recrystallization [6J. T h e active vermilion-red platelets, m.p. 2 5 0 ' C . (decomp.) [6], are soluble in ethyl ether, ethanol [1, 5, 6J, water LI. 6], carbon disulphide [5], acetone, chloroform [5, 6 J, benzene, hot ethyl acetate, and 10 p e r c e n t hydrochloric acid [6J; and insoluble in petroleum ether [1J and dilute aqueous acids and alkalis [ 6 j . T h e mol. wt. is 768-1,000 [6]- Actinomycin is stable to light and does not lose activity when subjected to boiling for 30 min. [6J. It is most stable in neutral or slightly acid solution, but activity lost through alkalinization is restored by subsequent neutralization [5], SPECTRUM.—The following microorganisms are inhibited in vitro by 0.05-0.2 m g / c c : Aspergillus Candida [5] Aspergillus niger [5] Azotobacter [5] Bacillus megatherium [7] Bacillus mesentericus [7] Bacillus mycoides [5, 6, 7] Bacillus subtilis [ 5 , 6 , 7 ] Diplococcus pneumoniae [7] Escherichia coli [4, 5 , 6 ] Flavobacterium sp. [7] Fusarium sp. [51 Humicola sp. [5] Mycobacterium phlei [7] Penicillium sp. [5 J Pseudomonas aeruginosa [5] Rhizopus sp. [5] Sarcina lutea [5, 6] Staphylococcus aureus [7] Streptococcus pyogenes [7] Trichoderma sp. [5] White yeast [5 J Actinomycin also inhibits the following: Achromobacter stutzeri [1] Actinomyces californicus [1] Actinomyces cellulosae [1] Azotobacter vinelandii [l] Bacillus cereus [1] Bacillus macerans [11 Bacillus polymyxa [1] Brucella abortus [ 1 ] Clostridium welchii [ 1 ] Cryptococcus neoformans [8] Erwinia carotovora [ 1 j Gaßkya tetragena [lj Hemophilus pertussis [11 Mycobacterium tuberculosis [1] Neisseria catarrhalis [1 I Pseudomonas fluorescent [ 11 Shigella gallinarum 11 ' Trichophyton mentagrophytes [8]

Actinomycin is bactericidal for Br. abortus, E. coli [1, 5), B. subtilis [1], and Sarcina lutea [5]. It also inhibits the growth of tomato roots and causes cytolysis of Paramecium, Glaucoma, and Colpidium [7). The following organisms are not inhibited in vitro by actinomycin: Aerobacter aerogenes [5]. Aspergillus clavatus [8] Candida albicans [8J Corynebacterium pyogenes [7] Dematium sp. [8] Erwinia tracheiphila [7] Erysipelothrix rhusiopathiae [7] Fusarium sp. [8] Hemophilus influenzae [7] Hemophilus suis [7] Pasteurella pseudotuberculosis [7] Penicillium luteum-purpurogenum [8] Phytomonas flaccumfaciens [7] Phytomonas phaseoli L7J Phytomonas ricinicola [7] Pseudomonas aeruginosa [7] Salmonella abortivoequina [7] Salmonella choleraesuis [ 7 ] Salmonella schottmuelieri [7] Serratia marcescens [7,8] Staphylococcus muscae [7] TOXICITY.—Actinomycin is highly toxic; 10 micrograms/20 gm mouse is lethal i.v., i.p., and s.c. 14, 5, 6j. The lethal dose for fowl is 0.5-1.0 mg/2.5 kg [5]. The M T D in mice is 5 m k / k g p.o. and 0.15 m g / k g i.V., i.p., or s.c. [9). See [1] Waksman and Woodruff, 1940a; [2] Welch, 1948; [3] Waksman, Geiger, and Reynolds, 1946; [4] Trussell and Richardson, 1948; [51 Waksman and Woodruff, 1941; [6] Waksman and Tishler, 1942; [7] Welsch, 1941; [8] Reilly et al, 1945; [9] Waksman, 1945.

actinomycosis,

clinical,

see

BACITRACIN;

PENI-

CILLIN.

actinorubln, an antibiotic derived f r o m an unidentified Actinomyces designated as Actinomyces A-105. It resembles A. erythreus, A. fradii, A. albosporeus, and A. californicus. T h e active material is purified by the same method used for LAVENDULIN. The assay of actinorubin is also the same as that of lavendulin. T h e m.p. of the helianthate derivative is 206°214°C. (corr., decomp.) [1]. Staphylococcus aureus is inhibited in vitro by 0.2-0.55 micrograms/cc [2], Escherichia coli also is inhibited by actinorubin [1]. TOXICITY— Mice weighing 17-19 gm survive i.v. injs of 0.25 mg for at least 14 days; 1.37 mg causes 100 percent mortality in 5 days. Survivors of large doses fail to gain weight normally or actually lose weight. At autopsy the kidney and liver are found to be damaged and the thymus and spleen are reduced in size. In some cases there is evidence of recovery from liver damage [2]. A BSORPTION.—Intraperitoneal injection of 1.3 mg of actinorubin in mice results in detectable quantities in the blood up to 75 min post inj. N o actinorubin is found in the blood as early as 15 min after administration of 3.43 m g to mice by stomach tube [2]. EXPERIMENTAL CLINICAL RESULTS. —When 17-19 gm mice are infected with 1 cc of a 10 ° dilution of Klebsiella pneumoniae, i.v. inj of 13.7 micrograms gives complete protection, and injection of 3.4 micrograms gives 60

Cross references are indicated by SMALL CAPITALS

A D A N S O N I A DIGITATA

[101

percent protection. With an infecting inoculum of 1 cc of a 10' 5 dilution of Klebsiella pneumoniae, i.v. inj of 30 micrograms protects 30 percent of the experimental mice, while inj of 2.5-5.0 micrograms is almost entirely ineffective [2]. See [1] Junowicz-Kocholaty and Kocholaty, 1947; [2] Morton, 1947a. Acta monta iUgtal», a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. A denla obtusa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See O s b o m , 1943. Adenoariymna nttJdum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Adenocarpus anagyrus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Adenostoma sparsifolium, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Adhatoda cydoniaefolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Adhatoda vasica, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Adían tum pedatum, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [ 1 | . In another series of tests in vitro aqueous extracts showed little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2]. See [1] Schnell and Thayer, 1949; [2] Hayes, 1947. Adonis autumnalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See O s b o m , 1943. Adonis vernalls, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. A doxa moschatellina, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aegle seplaria, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Aegopodhim podagraria, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aerobacter spp., as test organisms in vitro, see POLYMYXINS;

STREPTOMYCIN.

Aerobacter aerogenes.

1 As test organism in

.vitro, s e e ACTIDIONE; ACTINOMYCIN; ALLICIN; ANTIBIOTIC 1 3 6 ; ANTIBIOTIC 3 5 1 0 ; ANTIBIOTIC E l s ; ANTIBIOTIC X G ; ASPERGILLIC ACID; ASPERGILLIN; AUREOMYCIN; BACILLUS s p . ; BACILLUS LARVAE; BACITRACIN; BIOCERIN; CENTAUREA MACULOSA; CHAETOMIN; CHLORAMPHENICOL; CLAVACIN; FUMIGACIN; GLIOTOXIN; GRISEIN; HIRSUTIC ACIDS; K O J I C ACID; LF.PTOTAENIA M U L T I FEDA; LUPULON AND H U M U L O N ; NEOMYCIN; NOCARDIA GARDNERI; PERSOONIA PINIFOLIUS; POLYMYXINS; PSALLIOTA XANTHODERMA; P S E U DOMONAS F L U O R E S C E N S ; PTERYGOSPERMIN;

PUCHIIN; QUERCETIN; STREPTOLIN; STREPTOMYCES ANTIBIOTICUS; STREPTOMYCES AUREOFACIENS; STREPTOMYCES G R I S E U S ; STREPTOMYCES LAVENDULAE; STREPTOMYCES VENEZUELAE; STREPTOTHRICIN; SUBTENOLIN; S U B T I L I N ; SULFACTIN; TERRAMYCIN; TRICHOPHYTON M E N TAGROPHYTES; TRICHOPHYTON TONSURANS; T R I CHOPHYTON VIOLACEUM; XANTHOMYCINS A AND

B. For literature, see Burkholder and Evans, 1945 (lichens); Burkholder et al., 1944 (lichens); Cook and Lacey, 1945b ( f u n g i ) . 2 Effect of endotoxin in mice, see PENICILLIN. 3 Treatment of urinary infections, clinical, caused by, s e e AUREOMYCIN;

STREPTOMYCIN.

Aerobacter cloacae, as test organism in see

BACITRACIN.

see

STREPTOLIN.

vitro,

Aerobacter polymyxa, as test organism in vitro, Aerosporin, see POLYMYXINS.

Aeschynaothus javanka, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aesculus carnea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Aesculus hippocastanum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1J. In another series of tests in vitro aqueous extracts showed l i t t l e o r n o inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2], [1] Osborn, 1943; [2] Hayes, 1947. Aesculus parviflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aethlonema pulchellum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osbom, 1943. Aextoxicon punctatum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Aframomum melagheta, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Afrormosia laxiflora, a higher plant, extracts of the roots of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Agalinis purpurea, a higher plant, extracts of the flower, stem, and leaf, but not of the roots, of which are effective in vitro against Staphylococcus aureus. Only extracts of the stem and leaf inhibit Escherichia coli, and none of these extracts inhibits the spores of Neurospora crassa. See Schnell and Thayer, 1949. Agapetes buxifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Agapetes mannii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Agastache nepetoides, a higher plant, extracts of the leaves of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. Extracts of the seeds inhibit E. coli but not Staph, aureus. See Carlson, Douglas, and Robertson, 1948.

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[11] Agave sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Agave americana, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Agave attenuaU, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Ageratum houstonianum, a higher plant, extracts of the root but not of the flower, stem, and leaf of which are effective in vitro against the spores of Neurospora crassa. None of these extracts is effective against Staphylococcus aureus and Escherichia coli [1J. Aqueous extracts of this plant are also reported to be ineffective against Staph, aureus and E. coli [2]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Aglaia odorata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aglaooema pictum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Agonls flexuosa, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Agonls Unearifolia, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi [1,2J. See LI I Atkinson and Rainsford, 1949; [2 J Atkinson, 1949. agranulocytosis, clinical, see PENICILLIN. Agrimonia sp., a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumejaciens. See Hayes, 1947. Agrimonia eupatoria, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Agrimonia parviflora, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Agrimonia striata, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Agrobacterium spp., as test organisms in vitro, s e e LEPTOTAENIA DISSECTA; R H U S

HIRTA.

Agrobacterium tumefaciens, as test organism In vitro s e e STREPTOMYCES AMPHENICOL.

VENEZUELAE;

CHLOR-

Agrocybe dura, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. Against Staphylococcus aureus culture media are effective in vitro at 1:512. See Hervey, 1947. Agrocybe semiorbicularis, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Agropyrum repens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

ALCHEMILLA ARVENSIS

Agrostemma githago, a higher plant, aqueous extracts of w hich show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. Sec Hayes, 1947. A¡lanthus altisslma, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Ailanthus excelsa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Ailanthus glandulosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1J. Extracts of the wood are slightly effective against experimental malaria [2], See [1] Osborn, 1943; [2] Spencer et al., 1947. Ailanthus imberbiflora, a higher plant, extracts of the bark of which are effective in the treatment of experimental malaria. See Spencer et al., 1947. Aira caespitosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ajuga chamaepitys, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ajuga Iva, a higher plant, extracts of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Ajuga reptens, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and in vivo against experimental malaria [2]. See [1] Osborn, 1943; |2J Spencer et al., 1947. Akebia quinata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Alberta magna, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Alcaligenes spp., as test organisms in vitro, see AUREOMYCIN.

Alcaligenes fecalis. 1 as test organism in vitro, s e e ANT1SMEGMATIS FACTOR; BACILLUS VULGATUS; BACITRACIN; CENTAUREA MACULOSA; CHLORAMPHENICOL; EPIDERMOPHYTON FLOCCOSUM; KOJIC ACID; LUPULON AND H U M U L O N ; MYCOSUBTILIN; NOCAKDIA GARDNERI; ONCOPELTUS F A S C I A T U S ; PROTOANEMONIN; STREPTOMYCES ANTIBIOTICUS; STREPTOMYCES GRISEUS; STREPTOMYCES LAVENDULAE; STREPTOMYCES VENEZUELAE; SUBTILIN; SULFACTIN; T H U J A PLICATA; TRICHOPHYTON MENTAGROPHYTES; TRICHOPHYTON TONSURANS; TRICHOPHYTON VIOLACEUM.

For literature see Burkholder and Evans, 1945 (lichens); Burkholder et al., 1944 (lichens). 2 Treatment of u r i n a r y infections, clinical, c a u s e d by, see STREPTOMYCIN.

Alcaligenes metalcaligenes, as test organism in vitro,

see CHLORAMPHENICOL.

Alcaligenes viscosus, as test organism in vitro, s e e ANTIBIOTIC 1 3 6 , LUPULON AND H U M U L O N ; SUBTILIN; XANTHOMYCINS A AND B .

Alchemilla arvensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Cross references are indicated by SMALL CAPITALS

ALCHEMILLA VULGARIS

[12]

AkhemBIa vulgaris, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Alchornea ilicifoU», a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aiectoria chaiybeiformis, a lichen, extracts of which are effective in vitro against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Alcctryon excelsum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aleuria cevea, a fungus, extracts of the spirophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Aleuria subrepanda, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Wilkins, 1946a. Aleuria vesiculosa, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins. 1946a. Aleurisma lugdunense, a fungus which is effective in vitro against Staphylococcus aureus. See Pätiälä and Luteraan, 1947. Aleurites moluccana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Allsma plantago, a higher plant, concentrated aqueous extracts of the Chinese drug prepared from the root of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Gaw and Wang, 1949. Allsma plantago-aquatica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Allsma subcordatum, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Allamanda cathartica, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Allamanda cathartica v. hendersonll, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Allamanda neriifolia, a higher plant, aqueous extracts of which are effective in vitro against Stapylococcus aureus but not against Escherichia coli. See Osborn, 1943. Allescheria boydli, as test organism in vitro, see CHLORAMPHENICOL;

PROTOANEMON1N.

Alliaria officinalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. allkin, a colorless liquid antibiotic obtained by steam distillation from crushed cloves of the garlic. Allium sativum [1]. Although the name "allicin" has been withdrawn because of possible confusion with a medicinal product on the market, no other name for this substance has been proposed [2].

Analysis suggests the empirical formula CcHioOSa with the probable structure: Allyl-S-S-Allyl or Allyl-S-O-S-Allyl [3] Allicin is unstable to heat, stable under refrigeration, unaffected by dilute acid, and inactivated by alkali [1], It is also inactivated by cysteine [3, 4], It is soluble in water, ethyl alcohol, benzene, and ether [1]. Pure allicin has a garlic odor and is irritating to the skin [H. Allicin is effective in vitro against Streptococcus hemolyticus at 1:85,000 and the following organisms at 1:125,000 [1J: Bacillus subtilis Proteus morgani Salmonella enteritidis Salmonella paratyphi Salmonella schottmuelleri Salmonella typhi Salmonella typhimurium Shigella dysenteriae Shigella paradysenteriae Staphylococcus aureus Streptococcus viridans Vibrio cholerae Inhibition of Streptomyces griseus at 1:10,000, Aspergillus fumigatus and Penicillium cyclopium at 1:25,000, and the following organisms at 1:48,000 is also reported [5]: Aerobacter aerogenes Bacillus subtilis Escherichia coli Mycobacterium phlei Mycobacterium tuberculosis hominis Salmonella hirschfeldii Salmonella paratyphi Staphylococcus aureus The L D 5 0 for mice is about 60 mg/kg i.v. and 120 mg/kg s.c. [1], See [1] Cavallito and Bailey, 1944b; [2] Cavallito, Bailey, and Buck, 1945; [3J Cavallito et al., 1944; [4] Cavallito and Bailey, 1944a; [5] Rao, Rao, and Venkataraman, 1946. Allium ampeloprasum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Allium cepa, a higher plant (onion), various extracts of which are reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [lj, b) to inhibit Bacillus subtilis but not E. coli [2], and c) to inhibit Staph, aureus, E. coli, and Proteus X-19 [3], Yet a fourth extract, an aqueous, heatlabile preparation, is effective in vitro against E. coli, Brucella abortus, and Staph, aureus. The active substance, which is a resin, or gummy residue, is soluble in chloroform, ether, and benzene, and is inactivated by alkali. Chloroform extraction destroys the ability of the material to inhibit E. coli [4], This plant is also the source of PHYTONCIDES. See [1] Osborn, 1943; [2] Sanders et al., 1945; [3] Cardoso and Santos, 1948; [4] Huddleson et al., 1944. Allium cernum, a higher plant, extracts of various parts of which are effective in vitro against Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro the leaves inhibited Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens. The

C r o s s r e f e r e n c e s a r e indicated by SMALL CAPITALS

[13] leaf, stem, and flower were active against £>winia carotovora only, and the bulbs were active against Phytomonas tumefaciens. [2] See [1] Carlson and Douglas, 1948a; [2] Hayes, 1947. Allium ncapolitanum, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Allium pomim, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Allium sativum, a higher plant (garlic), aqueous, heat-labile extracts of which are effective in vitro against Escherichia coli, Brucella abortus, and Staphylococcus aureus. The active substance, which is a resin, or gummy residue, is soluble in chloroform, ether, and benzene, and is inactivated by alkali. Chloroform extraction destroys the ability of the material to inhibit E. coli. Paramecium caudatum is immobilized by the active principle in dilutions of 1:10,000. Guinea pigs are unaffected by i.p. injs of 85 mg of the material. Five mg doses i.p. twice a day are ineffective in Brucella suis infections in guinea pigs IllVarious other extracts of garlic are reported to inhibit Staphylococcus aureus [2], Escherichia coli [2, 31, and Bacillus subtilis | 3 | . It is also the source of the antibiotics ALLICIN and PHYTONCIDES. See [11 Huddleson et al., 1944; [2J Osborn, 1943; 13] Sanders et al., 1945. Allium schoenoprasum, a higher plant, various extracts of which are reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2] and b) to inhibit Staph, aureus but not Brucella abortus and E. coli [3]. See [1] Osborn, 1943; [2] Schnell and Thayer, 1949; [3] Huddleson et al., 1944. Allium tricoccum, a higher plant (wild garlic), aqueous, heat-labile extracts of which are effective in vitro against Escherichia coli and Staphylococcus aureus but not against Brucella abortus [1]. In another series of tests in vitro the leaves inhibited Staph, aureus, E. coli, Erwinia carolovora, and Phytomonas tumefaciens [2], See [1] Huddleson et al., 1944; [2] Hayes, 1947. Allium triquetrum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Allium ursinum, a higher plan*, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Allium vlneale, a higher plant, extracts of the flower, stem, and root of which are effective in vitro against Staphylococcus aureus and the spores of Neurospora crassa. Only extracts of the root inhibit Escherichia coli [II- in another series of tests in vitro the leaves and bulbs inhibited Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens. The leaf, stem, and flower were active against E. carotovora only [2], See (1] Schnell and Thayer, 1949; [2] Hayes, 1947. Allospondias lakonensls, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Alnicola escharoides, a fungus which is effec-

ALOE EBU

tive in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Alnicola melinoides, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Alnus firma v. sieboidiana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Alnus gludnosa, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Alnus mitchelliana, a higher plant, aqueous and ether extracts of the bud, ament, and leaf of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Alnus Orientalin a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Alnus rubra, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Alnus viridis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aloe afrlcana, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe arborescens, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe arista (a, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe barbadensis, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe brannthaleri, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe cameronli, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe candelabrum, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe chinensis, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe commutata, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe distans, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe eru, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949.

Cross references are indicated by SMALL CAPITALS

ALOE FEBOX

[141

Aloe ferox, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe «randhlentata, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe fcniwni«, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], Mycobacterium tuberculosis [1], and Proteus X-19 [2]. See [1] Gottshall et al., 1949; [2] Cardoso and Santos, 1948. Aloe mariotbl, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe mkrostigma, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe mitriformls, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe nobnis, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe plicatflls, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe robasta, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe saponaiia, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe spbioslssiina, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe striata, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Akte saccotrina, a higher plant, extracts of which are effective in vitro against Mycobacterium tuberculosis but not against Staphylococcus aureus and Escherichia coli. See Gottshall et al., 1949. Aloe thorncroftil, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe variegata, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe vera, a higher plant, ether extracts of the leaf of which are ineffective in vitro against Staphylococcus aureus, Escherichia coll, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Aloe vfrens, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aloe zebrina, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949.

Atopeeui us pratensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coll. See Osborn, 1943. Alophia sellowfana, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Aloysia triphylla, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Alpinla nutans, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Alsine longifolia, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Alstonia constricta, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Alstroemeria aurantfea, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Alstroemeria haemantha, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Alternanthera versicolor, a higher plant, ether extracts of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus and the spores of Nuerospora crassa. Aqueous extracts of this plant are ineffective against these three organisms. See Schnell and Thaver. 1949. Alternarla sp., a fungus which is ineffective in vitro against Staphylococcus aureus, Salmonella typhi, and Endomycopsis albicans. The culture media of this fungus are ineffective against Staph, aureus [1, 2] and Botrytis allii [1]. See [1] Brian and Hemming, 1947; [2] Cook and Lacey, 1945b. As test organism in vitro

s e e P S E U D O M O N A S FLUORESCENS;

MATOCYSTIS

STERIO-

sp.

Alternarla spp., as test organisms in vitro see ANTIBIOTIC

XG;

CHLORAMPHENICOL;

MUSARIN.

Alternaría citri, a fungus which is ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1942. For further reference, see Johns, 1947, unpublished. As test o r g a n i s m in vitro,

see ASPERGILLIC ACID;

ASPERGILLUS FACTOR; BERBERINE; C H E I R O L I N E ; CLAVACIN; L U P U L O N AND H U M U L O N ; MYCOPHENOLIC ACID; PENICILLIC ACID; PROACTINOM Y C I N ; RHIZOCTONIA FACTOR; T Y R O T H R I C I N .

Altemaria solani, a fungus which is ineffective in vitro against Staphylococcus aureus, Salmonella typhi, and Endomycopsis albicans. The culture media of this fungus are ineffective against Staph, aureus and Botrytis allii. See Brian and Hemming, 1947. As test organism in vitro s e e A C T I N O M Y C E S ANNULATUS; A C T I NOMYCES FLAVOVIRENS; ACTINOMYCES HALSTEDII; A C T I N O M Y C E S MADURAE; A C T I N O M Y C E S

VIRIDOCHROMOGENUS. For literature see Alexopoulos and Herrick, 1942 (actinomycetes). Alternaría tennis, a fungus effective in vitro in inhibiting the growth of Alternaría tenuis and Ophiobolus graminis. See Brömmelhues, 1935. Althaea fictfolla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

C r o s s r e f e r e n c e s a r e indicated by SMALL CAPITALS

115] Althaea officinalis a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Althaea rosea, a higher plant, extracts of the seed, seedling, and leaf of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Althaea sylvestris, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Altlngia excelsa, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Alvaradoa arborescens, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Alvaradoa jamaicensis, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. alveln, an antibiotic substance produced by the bacterium Bacillus alvei. It is extracted from the culture medium by adsorbing on charcoal, eluting with a butanol-hydrochloric acid mixture, extracting into water, and converting to the picrate and finally to the hydrochloride. Alvein hydrochloride is soluble in water and ethanol; and insoluble in acetone, chloroform, and ether. Elementary analysis indicates the following composition for the hydrochloride: C, 49.0; H, 8.7; N, 12.9; S, 1.2; CI, 8.9. It is stable at rm. temp, at pH 2, 7, and 9. The activity is unaffected by boiling for one hr at pH 2; at pH 9, half the activity is destroyed by boiling for one hr. Trypsin destroys the activity, but horse serum has very little effect. Chemical tests indicate that the free substance is a strongly basic polypeptide. Alvein hydrochloride is hemolytic. SPECTRUM — Alvein inhibits the following microorganisms: Inhibitory Microorganism concentration Bacillus anthracis 1:512,000 Corynebacterium diphtheriae gravis 1:128,000 Corynebacterium xerosis 1:8,000,000 Escherichia coli 1:32,000 Mycobacterium phlei 1:32,000,000 Mycobacterium tuberculosis 1:100,000 (4 days), 1:10,000 (11 days) Pseudomonas aeruginosa 1:16,000 Staphylococcus aureus 1:512,000 Streptococcus pyogenes 1:128,000 Attempts to develop resistant strains of Staph, aureus have been unsuccessful. See Gilliver et al., 1949. Alyssum maritlmum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Alyssum savatile, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Alyxia buxifoiia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Amanita aspersa, a fungus, extracts of the sporophores of which are ineffective in vitro

AMANITA VITTADINJI

against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Amanita echinocephala, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Amanita grisea, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Amanita mappa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Amanita muscaria, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [1,2], Escherichia coli [1,2], and Pseudomonas aeruginosa [11. See [1] Wilkins and Harris, 1944d; [21 Mathieson, 1946. Amanita ochrophylla, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, and Escherichia coli [1], Extracts of the fungus itself inhibit Staphylococcus aureus and Salmonella typhi [2], See [1] Mathieson, 1946; [ 2 ] Atkinson, 1949. Amanita pantherlna, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Amanita pantherlna f. robusta, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Amanita phailoides, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Amanita porphyria, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Amanita rubescens, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [ 1J. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Wilkins, 1947c; [2] Wilkins and Harris, 1944d. Amanita solitaria, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Pseudomonas aeruginosa but not against Escherichia coli. See Wilkins and Harris, 1944d. Amanita spissa, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2]. See [1] Wilkins, 1947c; [2] Wilkins and Harris, 1944d. Amanita virosa, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Amanita vittadinli, a fungus, the culture media of which are effective in vitro against Staphy-

Cross references are indicated by SMALL CAPITALS

AMANTTOPSIS FULVA lococcus aureus but not against Escherichia coli. See Wilkins, 1947c. A a m k o p d i fnlra, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. A — nkopri« pakhdla, a fundus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coll. See Mathieson, 1946. Amanitoprii strangulate, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Amaattapds mbiutea, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Aounbopsb vagkuta, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [ 1 , 2 ] , Escherichia coli [ 1 , 2 ] , and Pseudomonas aeruginosa [1]. See [1] Wilkins and Haris, 1944d; [ 2 ] Mathieson, 1946. Amarantn« bUtnm, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Amarants* candabu, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Amarantns cMorortachys, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Amarantes hypochondria ras, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Amarantns retroflexos, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Other extracts inhibit Staphylococcus aureus and Escherichia coli but not Mycobacterium tuberculosis [2], See [1] Osborn, 1943; [2] Gottshall et al., 1949. Amarantns tricolor, a higher plant, aqueous and ether extracts of the leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Amarantns viridis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Amaryllis belladonna, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [2], Extracts of the bulbs are effective in the treatment of experimental malaria [3]. See [11 Osborn, 1943; [2] Gottshall et al., 1949; [3] Spencer et al.. 1947. Amaryllis hybrid, a higher plant, extracts of the flower and leaf of wnich are effective in vitro against Staphylococcus aureus and Escherichia coli but not against spores of the fungus Neurospora crassa. See Schnell and Thayer, 1949. Amaaoaia arborta, a higher plant, aqueous extracts of which are ineffective in vitro against

Staphylococcus aureus and Escherichia coll. See Osborn, 1943. Ambrosia artemesiaefolia, a higher plant, extracts of which are ineffective against experimental malaria [1], In a series of tests in vitro aqueous extracts showed little or no inhibition of growth against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens [2], See [11 Spencer et al., 1947; [2] Hayes, 1947. Ambrosia elatior, a higher plant, extracts of the leaf of which are reported to be ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1], Other investigators report that extracts of this plant inhibit Bacillus subtilis and E. coli [2]. See [1] Schnell and Thayer, 1949; [2] Sanders et al., 1945. Ambrosia trífida, a higher plant, some extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli; other extracts inhibit Staphylococcus aureus and E. coli [2]. In another series of tests in vitro aqueous extracts caused little or no inhibition of growth of Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [3], See [1] Sanders et al., 1945; [2] Carlson, Douglas, and Robertson, 1948; [3] Hayes, 1947. Ameba proteus, as test organism in vitro, see PYO COMPOUNDS.

amebiasis, clinical, see AUREOMYCIN; PENICILLIN; STREPTOMYCIN.

amebic colitis, see BACITRACIN. Amelanchler alntfolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Amelanchler canadensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Amellas annous, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Amorpha fruticosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Amorphophailus rivleri, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ampelamus albidus, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et aJ., 1945. Ampélopsis cordata, a higher plant, extracts of the leaf and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Ampélopsis veitcbil, a higher plant, extracts of the root, stem, leaf, and entire plant of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. amphibia, animals, extracts from whose tissues are reported as possessing antibacterial activity. See Pavan, 1949. Amphltecna nigripes, a higher plant, aqueous extracts of which a r e i n e f f e c t i v e in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Cross references are indicated by SMALL CAPITALS

ANACARDIC ACID

[17] Amsonia tabernaemontana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Amyris elemifera, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. anacardic acid, an antibiotic isolated from Anacardium occidentale, the tropical tree from the fruit shell of which cashew-nut oil is obtained. The compound, which is slightly soluble in water and soluble in ethyl alcohol and ether, has the empirical formula C^Hai'Ch and the structural formula 2-hydroxy-6 pentadecadienyl benzoic acid: C O Q H

-As

CisHJ7-

OH

Anacardic acid is effective in vitro in inhibiting the growth of the following in the concentrations given: Organism Concentration Bacillus anthracis 1:20,000 Brucella melitensis 1:2,000 Mycobacterium tuberculosis (human strain "Ratti") 1:20,000 Neisseria gonorrhoeae 1:20,000 Pasteurella aviseptica 1:2,000 Penicillium nolatum 1:200 Proteus X-19 1:200 Staphylococcus hemolyticus aureus 1:20,000 Streptococcus pyogenes 1:200,000 Anacardic acid is ineffective in vitro in concentrations of 1:200 against the following: Asperillus niger Bacillus pyocyaneus Escherichia coli Salmonella paratyphi B Salmonella typhi Yeast (strain isolated from the air) The vegetative forms of anaerobic bacteria (Clostridium tetani, CI. perfringens, CI. septicum) are readily killed even by high dilutions of sodium anacardate. The spores of CI. tetani and CI. septicum survive even a prolonged contact (1 hr) with a 1:100 sodium anacardate solution, whereas the spores of CI. perfringens and aerobic bacilli (Bacillus anthracis, B. subtilis) are very sensitive. Molds and yeasts, with few exceptions, are very resistant. Spirochaeta gallinarum is highly sensitive to the action of sodium anacardate. Cardol, the structural formula of which is: HO-

A

C15H27

V OH and anacardol, the structure of which is: HO A s

V

C15H27

are both isolated, along with anacardic acid, from Anacardium occidentale. Both are effec-

tive in vitro in preventing the growth of Staph, hemolyticus aureus. In vitro experiments showed a high vermicidal activity of sodium anacardate. Rhabditis fuelleborn (nematodes) died within 30 min in a 1:100,000 solution; cestoids (from the rat intestine), in a 1:4,000 solution after 15 min; ascarids (from the swine intestine), only in a 1:100 solution after 15 min, surviving in a 1:5,000 solution for more than 2Vi hr. Protozoa from a hay infusion showed a varying degree of sensitiveness to sodium anacardate. Ciliates died within 10-12 min in a 1:30,000 solution. Ameboid forms became immobile after 10 min in a 1:5,000 solution. Some flagellates became immobile in a 1:3,000 solution after 20 min; others survived in the same solution for more than IVi hr. Larvae of culicidae were killed within 2 hr. by a 1:20,000 solution of sodium anacardate. TOXICITY.—Sodium anacardate and the related compounds (cardol and anacardol) do not produce any systemic lesion when given by the oral route. Intravenous injs in concentrations of 1:100 and greater produce anaphylactoid shock in guinea pigs and pigeons. Subcutaneous injs of a 1% oily solution are well tolerated; other solutions of this strength cause sterile necrosis. Ointments (2-5%) produce transitory loss of hair in rabbits, but this local effect has not been observed in human subjects. Sodium anacardate has a strong hemolytic activity, which is considerably reduced in the presence of serum. Leukocytes are less sensitive to the cytolyzing activity of the compound. Intravenous inj of 1-2 cc of a 1% sodium anacardate solution is fatal to guinea pigs in a few seconds, the animals dying with the symptoms of anaphylactoid shock. Slow inj of 5-10 cc of a 1% solution into the ear vein oi rabbits causes unrest, dyspnea, and lassitude in some of the animals, but these symptoms disappear after about 30 min. Only when the injs occured rapidly did the rabbits die in shock with opisthotonos and clonic convulsions. These injs caused thrombosis of the ear vein and sometimes sterile necrosis of the surrounding tissue in a number of instances. Pigeons tolerated i.v. inj of 1 cc of a 1% solution without special symptoms, whereas higher concentrations (2.5-5%) killed the animals after 3-5 min, with symptoms not unlike those provoked by neurotoxic snake venoms; i.e., opisthotonos and clonic convulsions. The instillation of a 1% sodium anacardate solution into the conjunctival sack of rabbits did not reveal any irritating action during an observation time of 24 hr. The instillation of a 0.2-1% solution of the compound into the male urethra caused a burning sensation of varying intensity in various individuals tested. EXPERIMENTAL CLINICAL RESULTS IN ANIMALS.—Anthelmintic effects in vivo could be observed in rats, guinea pigs, and rabbits which received the sodium anacardate orally. Rabbits heavily infested with scabies were cured by local application of a 5% ointment of either raw cashew-nut oil or sodium anacardate. Transitory loss of hair occurred in the treated parts. EXPERIMENTAL CLINICAL RESULTS IN HUMAN BEINGS.—Intraurethral instillations of a 0.2% solution of sodium anacardate are generally well supported. Preliminary ex-

Cross references are indicated by

SMALL CAPITALS

ANACARDIUM OCCIDENTALE

[

periments on the local treatment of specific and unspecific urethritis and other pyogenic infections gave encouraging results. See Eichbaum, 1946; Eichbaum et al., 1945. Anacardhim occidental«, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. See also ANACARDIC ACID. Anacychu maroccanus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Anacychu pyrethrum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. anaerobic streptococcus, as test organism in vitro, see MICROCOCCIN. A nagall« arvensls, a higher plant, aqueous extracts of the flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [ 1 ] , Aqueous extracts of this plant are also reported to be ineffective against Staph, aureus and E. coli [2]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Anagyris foetida, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Anamirta coccuius, a higher plant, various extracts of which are effective in vitro against Mycobacterium tuberculosis [1 ] but not against Staphylococcus aureus [ 1, 2 ] and Escherichia coli [1, 2], See [1] Gottshall et al., 1949; [21 Osborn, 1943. Anap halls margaritacea, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Anchusa capensis, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus. Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Anchusa Italica, a higher plant, extracts of the leaf and stem (but not of the flower and root) of which are effective in vitro against Staphylococcus aureus. Only extracts of the flower inhibit Escherichia coli, and none of these extracts inhibits the spores of Neurospora crassa [ 1 ] , Aqueous extracts of this plant are also reported to be ineffective against Staph, aureus and E. coli [2], See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Anchusa myosotidiflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Anchusa sempervlrens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Andrographis paniculata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn. 1943. Andropogon mlnarum, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Andropogon schoenanthus, a higher plant, aqueous extracts of which are ineffective in vitro

] against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Androsace sannentosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Androsacens androsaceus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Androsaceus rotula, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Andryala varia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aneimia phyllttidis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Anellaria separata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Anemarrhena asphodeloides, a higher plant, concentrated aqueous extracts of the Chinese drug prepared from the root of which are effective in vitro against Staphylococcus aureus but not Escherichia coli. See Gaw and Wang, 1949. Anemone apennlna, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Anemone blanda v. synthimica, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Anemone canadensis, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Anemone chinensis, a higher plant, concentrated aqueous extracts of the Chinese drug prepared from the root of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Gaw and Wang, 1949. Anemone hepatica, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al.. 1949. Anemone nemorosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Ösborn, 1943. Anemone occidentals, a higher plant, the mountain pasque, extracts of which are effective in vitro against Staphylococcus aureus. Two-week-old chicks injected with the extracts mixed with blood containing Plasmodium xallinaceum fail to develop malaria. The extracts are ineffective in the treatment of experimental malaria in chicks but have some protective effect against Diplococcus pneumoniae infections in mice. Doses of 0.5 to 1.0 cc injected i.p., s.c., or

Cross references are indicated by SMALL CAPITALS

[191 i.v. in chicks and mice are lethal. See Carlson, Bissell, and Mueller, 1946. Anemone Pulsatilla, a higher plant, aqueous extracts of which are effective in vilro against Staphylococcus aureus and Escherichia ci>li. See Osborn, 1943. See also PROTOANEMONIN. Anemone ranuncnloides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Anemone rupicola, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Anemone " S t Brigid," a higher plant, aqueous extracts of the garden hybrid of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. anemonin, a lactone found in plants and effective in vitro against certain bacteria, molds, and yeasts, is the dimer of PROTOANEMONIN. Growth of Staphylococcus aureus and Shigella dysenteriae is i n h i b i t e d with dilutions of 1:12,500. Growth of Escherichia coli is unaffected. It is also reported that a dilution of 1:50,000 of anemonin prevents in vitro the growth of Trypanosoma equiperdum. Chemically anemonin is 3 pentene-1, 4-olide, crotonolactone gamma acetic acid. TOXICITY.—Solutions are irritating when instilled into the eyes of rabbits. Venospasm occurs after i.v. inj. In cats, i.v. inj is followed by a transitory fall in blood pressure. Eight successive 50 mg/kg ¡.p. doses were tolerated without loss in weight. EXPERIMENTAL CLINICAL RESULTS. —100 mg/kg of anemonin injected i.p. failed to protect mice from shigella peritonitis. See McCawley et al., 1946. Anemopsis califomlca, a higher plant, extracts of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Anethnm graveolens, a higher plant, extracts of the seed and seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Angelica sp., a higher plant, concentrated aqueous extracts of the Chinese drug prepared from the root of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Gaw and Wang, 1949. Angelica arguta, a higher plant. Extracts of the roots are effective in vitro against Staphylococcus aureus and Escherichia coli. Extracts of the seeds and stems inhibit E. coli but not Staph, aureus. See Carlson, Douglas, and Robertson, 1948. angina, Lodwig's clinical, see PENICILLIN. Angophora intermedia, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi [ 1 , 2 ] . See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Anisomeris obtusa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Anisotes dlversifollus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Annesiia eriophylla, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947.

ANTHOXANTHUM

ODORATUM

Annona cherimolia, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Annona foetida, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Annona muricata, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [ 1J and in vivo against experimental malaria [2]. See [1] Osborn, 1943; [2] Spencer et al., 1947. Annona squamosa, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli [1], Other extracts are ineffective against Staph, aureus, E. coli, and Proteus X-19 [2]. See [1] Osborn, 1943; [2] Cardoso and Santos, 1948. Anogeissus latifolia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Antennaria dioica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Antennaria parlinii, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Antennaria plantaginifoila, a higher plant, extracts of which are effective in vilro against Escherichia coli but not against Staphylococcus aureus [1], In another series of tests in vitro aqueous extracts showed little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2]. See [1] Carlson, Douglas, and Robertson, 1948; [2] Hayes, 1947. Anthemis cotola, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Other extracts inhibit Staph, aureus but not E. coli [2]. See [1J Osborn, 1943; [2] Carlson, Douglas, and Robertson, 1948. Anthemis nobilis, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1,2], Escherichia coli [1,2], and Mycobacterium tuberculosis [2]. See [1] Osborn, 1943; [2] Gottshall et al., 1949. Anthemis tinctoria, a higher plant, aqueous extracts of the seed and seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Aqueous extracts of this plant are also reported to be ineffective against Staphylococcus aureus and Escherichia coli [2], See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Anthocercis viscosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Anthocleista frezoulsii, a higher plant, extracts of the bark of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Anthostomella sp., as test organism in vitro, see ACTINOMYCES ALBUS; BACILLUS SUBTILIS; RATIA MARCESCENS.

SER-

Anthoxanthum odoratum, a higher plant, aque-

Cross references are indicated by SMALL CAPITALS

[20]

ANTHRAX, CLINICAL

ous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. antkrax,

«•»»•»«••i,

see

PENICILLIN;

STREPTOMY-

A n t M K a s aylf««tob, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aathorium u d r t a n o n v. album, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Anthorium crystalllnam, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. A n t h o n u rothae, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Anthyllb montana v. rubra, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. AnthyUb vnlnerarta, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Antiaris toxlcaria, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. antibacHlin, an inhibitor of BACILLIN, which occurs universally in biological systems. It is found in the free state in milk (both fresh and dried) and in the mycelia of Penicillium notatum and Streptomyces griseus and is liberated f r o m gelatin and casein on hydrolysis. The activity of antibacillin is not due to the presence of sulphur or the sulphydryl groups, nor does the substance combine with or destroy bacillin. It probably acts by competing with bacillin for vital systems in susceptible microorganisms. See Woodruff and Foster, 1946a. antibiotic 136, an antibiotic substance produced by a strain of Streptomyces lavendulae. It is extracted from the clarified culture filtrate by adsorbing on Folin Dec also at p H 7.S, eluting with ammonium chloride solution, reabsorbing on Darco G-60, and eluting with hydrochloric acid in aqueous methanol. The eluate is concentrated in vacuo and filtered, and the active material is precipitated with acetone and dried in vacuo. The preparation contains both acid and basic groups and loses about 10% of its activity on boiling at pH 2.0 for 1 hr. SPECTRUM— Antibiotic 136 is inhibitory in vitro for the following organisms: Dilution units/ gm Bacteria (x 1,000,000) A erobacter aerogenes 16-18 Alcaligenes viscosus 40 Bacillus cereus 1 Bacillus mesentericus 30 Bacillus mycoides 10 Bacillus polymyxa 20 Bacillus subtilis 4, 20, 140 Brucella abortus 3 Escherichia coli 4-14 Gaffkya tetragena 120 Hansenula anomala 3 Mycobacterium tuberculosis 0.3 Phytomonas campestris 60

Bacteria Proteus vulgaris Pseudomonas aeruginosa Pseudomonas fluorescens Salmonella enteritidis Salmonella schottmuelleri Salmonella suipestifer Salmonella typhi Serratia marcescens Shigella gallinarum Staphylococcus albus Staphylococcus aureus Staphylococcus citreus Streptococcus hemolyticus

Dilution units/ gm ( x 1,000,000) 3.5 1.2 1.2 6 14 50 7 0.8 12 ¿0 30-50 180 1

Dilution units/gm Fungi (x 1,000) Candida albicans 20 Coccidioides immitis 12 Cryptococcus neoformans 80 Epidermophyton floccosum 8 Geotrichum sp. 12 Hormodendrum compactum 24 Hormodendrum pedrosoi 20 Microsporum audouini 2 Monosporium apiospermum 2 Nocardia asteroides 4 Phialophora verrucosa 20 Sporotrichum schenckil 4 Trichophyton rubrum 24 TOXICITY.—'The i.v. and s c. LDso in 18-20 gm mice is about 0.2 mg. Mice survive oral doses of 2 mg without signs of toxicity. EXPERIMENTAL CLINICAL RESULTS. —Mice with pneumococcal infections are not benefited by 0.1 mg s.c. or 1 mg p.o. See Bohonos et al., 1947. antibiotic 3510, a grisein-like antibiotic produced by a strain of Streptomyces griseus. Isolation of this agent is accomplished by a method similar to that used for the extraction of grisein. Antibiotic 3510 is not affected by cysteine, glucose, or horse serum. Although iron in the medium of the producing organism favors the production of the active substance, the presence of iron in the test medium reduces the in vitro activity of the agent. There is evidence that this strain of S. griseus may also produce an antimycobacteria factor. SPECTRUM — Antibiotic 3510 inhibits both streptomycin- and grisein-resistant strains of Escherichia coli. In addition, it inhibits Bodenheimer's organism, which is not affected by streptomycin or grisein. It is also effective, to the extent indicated, against the following organisms. Units/mg crude Organism dry preparation A erobacter aerogenes less than 0.05 Bacillus circulans less than 0.05 Bacillus mycoides less than 0.05 Bacillus sublilis 4 Candida albicans less than 0.05 Cryptococcus neoformans 0 Escherichia coli 12 Escherichia coli (streptomycin resistant) Micrococcus lysodeikticus Mycobacterium tuberculosis Proteus vulgaris Pseudomonas fluorescens Salmonella pullorum Sarcina lutea Serratia marcescens

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

20 less than 0.05 less than 0.05 less than 0.05 less than 0.05 more than 120 less than 0.05 less than 0.05

[21] Units'mg crude dry preparation Organism 12 Shigella alkalescens 40 Shigella dysenteriae Shigella paradysenleriae more than 120 Staphylococcus aureus more than 40 Trichophyton mentagrophytes 0.4 EXPERIMENTAL CLINICAL RESULTS. —Antibiotic 3510 is more effective than streptomycin against Salm. pullorum infections in chick embryos. See Garson and Waksman, 1948. antibiotic Els, an antibiotic substance produced by Streptomyces Els. The purified compound is obtained as a fine white precipitate. It resembles actinorubin in its spectrum, general properties, and toxicity. Antibiotic Els is assayed in terms of dilution units, with Escherichia coli communior as the test organism. The producing organism is effective in vitro against the following microorganisms: Achromobacter sp. Aerobacter aerogenes Bacillus sp. Bacillus cereus Bacillus megatherium Bacillus mycoides Bacillus subtilis Corynebacterium xerosis Escherichia coli communior Micrococcus aureus Sarcina lutea Serratia marcescens The active principle inhibits Mycobacterium tuberculosis and Mycobacterium phlei in dilutions of 1:100,000 and 1:500,000, respectively. It is also effective against B. subtilis, E. coli, and Micrococcus aureus. Intraperitoneal inj of 150,000 to 270,000 units/kg in 20-35 gm mice results in death of 1/10 in 5 days. Other experimental animals sacrificed 5-19 days after inj showed necrosis of the liver and renal epithelial damage. See Weiser et al„ 1949. antibiotic " F , " an antibiotic material isolated from a Streptomyces sp. It is a mixture of two or more antibiotic substances, one of which appears to be identical with streptomycin. A second fraction is similar to streptothricin. See Trussell et al., 1947. antibiotic H-3, an antiphage substance found in the culture liquors of an unidentified Aspergillus. Extraction of neutral culture filtrates with chloroform yields an active brownish-yellow gum which may be dried to a powder in vacuo. TTie powder is soluble in most organic solvents, stable to heat and acid, but unstable to alkali. The unit of activity is measured in terms of inhibition of Staphylococcus aureus phage. A preparation containing 270 units/mg inhibits Streptococcus fecalis at 300 micrograms/ cc, Bacillus subtilis at 100 micrograms/cc and Staph, aureus at 30 micrograms/cc. Concentrations of 300 micrograms/cc are without effect on Escherichia coli, Salmonella schottmuelleri, Klebsiella pneumoniae. Brucella bronchisepticus, and Mycobacterium tuberculosis hominis. Concentrations of less than 100 micrograms/cc are ineffective against the fungal pathogens of man. The s.c. LD50 is about 9.6 mg/mouse. Seven s.c. doses of 3 mg each over a period of 3.5 days hasten death in mice infected with polio-

ANTIBIOTIC X G

myelitis or influenza. See Hanson and Eble, 1949. antibiotic "V," an antibiotic substance produced by a strain of Streptomyces lavtndulae. It is inhibitory in vitro tor the following organisms: Organism Inhibitory concentration units/cc Bacillus cereus more than 50 Bacillus mycoides 15 Bacillus subtilis 0.2 Candida albicans 40 Escherichia coli 2 Mycobacterium 607 1 Mycobacterium butyricum 0.5 Mycobacterium phlei 0.6 Mycobacterium tuberculosis 20 Mycobacterium tuberculosis avium 0.8 Proteus vulgaris 0.5 Pseudomonas fluorescent 20 Serratia marcescens 20 Staphylococcus aureus 1 Trichophyton mentagrophytes 15-30 See Hutchison, et al., 1949. antibiotic XG, an antibiotic substance found in culture filtrates of Bacillus subtilis X G [1]. It is adsorbed from the media on charcoal and eluted with aqueous acetone. It is soluble in methanol and ethanol and insoluble in ether, chloroform, ethyl acetate, and dry acetone. At pH 7, it withstands autoclavmg at 15 lb pressure for 10 min [2]. Associated with the active substance, which is an amphoteric olypeptide [2], is a hemolytic principle 1,2]. The unit of activity is the least amount of antibiotic which will inhibit the growth of a standard strain of Trichophyton gypseum under controlled conditions [1,2], SPECTRUM.—Culture filtrates from Bacillus subtilis XG inhibit the following organisms in vitro [1]: Acladium spp. Alternaria spp. Aspergillus nidulans Aspergillus niger Bacillus subtilis Chaetomium spp. Fusarium spp. Hormodenarum olivaceum Microsporum audouini Microsporum fulvum Microsporum lanosum Monilia albicans Mycoderma spp. Pneumococci Sporotrichum schenckli Streptococcus hemolyticus Torula spp. Trichoderma spp. Trichophyton crateriforme Trichophyton gypseum Trichophyton purpureum Staphylococcus aureus is not affected by dilutions of 1:10 [1]. The following organisms are inhibited by the antibiotic in the concentrations shown [2]: Organism Units/cc required for inhibition Pathogenic fungi Cryptococcus neoformans 1.4 Epidermophyton floccosum 2.8 Microsporum audouini 11.2 Microsporum canis 0.7 Monilia albicans 1.0

f

Cross references are indicated by SMALL CAPITALS

ANTIDESMA BUNIUS

[22]

Organism Units/cc required Pathogenic fungi for inhibition Rhodolorula sp. 1.4 Sporotrichum schenckii 11.2 Trichophyton gypseum 2.8 Trichophyton rubrum 11.2 Bacteria Aerobacter aerogenes more than 315 Brucella bronchisepticus less than 1.7 Diplococcus pneumoniae 2.0 Escherichia coli more than 315 Klebsiella pneumoniae more than 315 Proteus vulgaris more than 315 Pseudomonas aeruginosa more than 315 Salmonella paratyphi more than 315 Salmonella typhi more than 315 Staphylococcus aureus more than 315 Streptococcus hemolyticus 4.0 See [1] Lewis et al., 1946; [2] Hobby et al., 1949. Antidesma bunhis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Antirrhinum asarina, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Antirrhinum majas, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Antirrhinum maximum grandiflonim, a higher plant, extracts of the flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Antirrhinum speciosum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. antlsmegmativ factor, an antibiotic produced by an unidentified sp. of the genus Actinomyces, closely resembling A. lavendulae. Partial concentration is achieved by freezing and then slowly thawing the culture filtrate. Crude filtrates withstand boiling for 30 min at pH 7.0. SPECTRUM— A filtrate effective at 1:1,280 against Mycobacterium smegmatis (the standard test organism) fails to inhibit the following at 1:10: Alcaligenes fecalis Bacilli Brucellae Chromobacterium violaceum Clostridia Corynebacteria Escnerichiae Gaffkya tetragena Klebsiella pneumoniae Micrococci Mycobacterium tuberculosis bovis Neisseria catarrhalis Neisseria sicca Proteus vulgaris Pseudomonas vulgaris Salmonellae Serratia marcescens Shigellae Staphylococci Streptococci Trichophyton interdigitale Vibrio comma

A preparation containing 2,000 dilution units/ cc is ineffective at 1:10 against Aspergillus niger, A. oryzae, and Candida albicans; it is effective at 1:10 but not at 1:20 against Bacillus subtilis. It inhibits a nonpathogenic Myco, tuberculosis hominis at 1:40 and Myco, phlei at 1:400. TOXICITY.—Two cc of a filtrate containing 2,000 dilution units/cc have no apparent effect when injected i.p. in 17-20 gm mice. See Keiner and Morton, 1946. Aphanomyces spp., as test organisms in vitro, s e e BACILLUS SP.

Aphanopetalum resin osum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aphyllanthes monspeliensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Apios amerkana, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Apis mellifica, the honey bee, the blood of which has been shown not to contain the antibiotic INSECTICIN. Aphim graveolens, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [ 1 , 2 J , Escherichia coli [ 1 , 2 ] , and Proteus X-19 [2], Aqueous and ether extracts of the leaf, stem, and root are ineffective a g a i n s t Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [3], Extracts of this plant are also reported to be ineffective in vivo against experimental malaria [4]. See [1] Osborn, 1943; [2] Cardoso and Santos, 1948; [3J Schnell and Thayer, 1949; [41 Spencer et al., 1947. Apocynum androsaemifollom, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Apocynum cannablnum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Other extracts inhibit E. coli but not Staph, aureus [2], and yet other extracts are ineffective against experimental malaria [3]. In another series of tests in vitro aqueous extracts showed little or no inhibition of growth against Staph, aureus, E. coli, Envinia carotovora and Phytomonas tumefaciens [4], See [11 Osborn, 1943; [2] Carlson, Douglas, and Robertson, 1948; [3J Spencer et al., 1947; [4] Hayes, 1947. Apocynom venetum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Apollonias canariensls, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aquilegia alpina, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aquilegia canadensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

C r o s s r e f e r e n c e s a r e indicated by SMALL CAPITALS

[23] Aquilegia chrysantha, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aquilegia helenae, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aquilegia hybrid, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli See Osborn, 1943. Aquilegia vulgaris, a higher plant, aqueous extracts of the seed of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Aqueous extracts of this plant are also reported to be ineffective against Staphylococcus aureus and Escherichia coli [2]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Arabidopsis thaliana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Arabis albida, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Arabis alpina, a higher plant, aqueous extracts of the seed of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thaver, 1949. Arabis caucasica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Arabis birsnta, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas lumefaciens. See Hayes, 1947. Araiia nudicaulis, a higher plant, aqueous extracts of the fruit and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other extracts of this plant are reported to be ineffective against Staph, aureus, E. coli, and Mycobacterium tuberculosis [2]. See [1] Schnell and Thayer, 1949; [2] Gottshall et al., 1949. Araiia spinosa, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Araucaria angustifoiia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Araucaria cookii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Araucaria excelsa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Araujia sericifera, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Arbutus canadensis, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

ARCTIUM MINUS

Arbutus unedo, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Arclungelica officinalis, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Arctium sp., see BURDOCK.

Arctium lappa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Concentrated aqueous extracts of the Chinese drug prepared from the seeds of this plant are also ineffective against Staph, aureus and E. coli \2\. See [1] Osborn, 1943; [2] Gaw and Wang, 1949. Arctium minus and Onopordon taurlcum, higher plants from which one or more antibiotic substances are extracted. One substance is extracted from the ground leaves with water; the filtrate is adjusted to pH 3, boiled, centrifuged, extracted with ether, passed through an alumina column, and crystallized by refrigeration. It is a neutral compound, crystallizing in small, optically active, orthorhombic plates which are soluble in ethanol, acetone, ethyl acetate, and chloroform; sparingly soluble in water and ethyl ether; and insoluble in petroleum ether. The mol. wt. is 336, and the probable formula, Cm H24 On. Staphylococci are inhibited in vitro by 0.5 mg/cc; 2 m g / c c are ineffective against Escherichia coli [1]. This compound is probably an isomer of the one derived from A. minus [2] described below. The second antibiotic principle is obtained as large, optically active prisms, which decompose on slow heating and have the probable formula (C.i H< 0 ) x . They are soluble in methanol, ethanol, chloroform, ethyl acetate, dioxane, and acetone; slightly to moderately soluble in ether, benzene, and water; and insoluble in Skellysolves. The antibacterial activity of this compound is destroyed by cysteine and N-acetylcysteine, but not by S-methylcysteine. SPECTRUM.—Streptococcus viridans is inhibited in vitro by 1 mg/cc. The following are inhibited by 0.7 mg/cc or less: Bacillus subtilis Clostridium botulinum Clostridium oedematiens Clostridium perfringens Clostridium septicum Clostridium tetani Pneumococci Staphylococcus albus Staphylococcus aureus Streptococcus hemolyticus The following are not inhibited by 1 m g / c c : Escherichia coli Proteus morgani Proteus vulgaris Salmonella enteritidis Salmonella paratyphi Salmonella schottmuelleri Salmonella typhi Salmonella typhimurium Shigella flexneri Shigella sonnei TOXICITY.—The parenteral LD50 in mice is about 90 mg/kg. Daily oral doses of 100 mg/kg in mice for 8 days are without ill effect; 500 mg/kg causes loss of weight but no deaths.

Cross references are indicated by SMALL CAPITALS

ARCTOSTAPHYLOS UVA-URSI

[24]

EXPERIMENTAL CLINICAL RESULTS. —Doses of 50-250 m g / k g s.c. in mice fail to protect against Strep, hemolyticus infections. Various other extracts of A. minus are reported a ) t o be effective in vitro against B. subtilis and E. coli [3], b ) to inhibit Mycobacterium tuberculosis but not Staph, aureus and E. coli [4], and c) to inhibit Staph, aureus but not E. coli [5]. See [1] Abraham, Crowfoot, Joseph, and Osborn, 1946: [2J Cavallito, Bailey, and Kirschner, 1945; [3] Sanders et al., 1945; [4] Gottshall et al., 1949; [5] Carlson, Douglas, and Robertson, 1948. Arctostaphylos nva-nrsi, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Arctotfa grandis, a higher plant, aqueous extracts of the flower and leaf of which are effective in vitro against Staphylococcus aureus; aqueous extracts of the stem and root and ether extracts of all these parts are ineffective. Escherichia coli is inhibited only by ether extracts of the flowers. It is demonstrated, however, that the spores of Neurospora crassa are not affected by any of these extracts. See Schnell and Thayer, 1949. Arctotis stoechadifolla, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Ardfala crisp«, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ardlda henryi, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ardlsia homilis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ardisia opegrapha, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Arenaria serpyllifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Arenaria tetraquetra, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Arenaria trinervis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Argemone hybrlda grandiflora, a higher plant, aqueous extracts of the root and flower but not of the stem of which are effective in vitro against Escherichia coli. Only extracts of the flower inhibit Staphylococcus aureus, and none of these extracts, however, inhibits the spores of Neurospora crassa. See Schnell and Thayer, 1949. A n e m o n e mexlcana, a higher plant, extracts of which a r e ineffective against experimental malaria. See Spencer et al., 1947. Argyrela walllchl, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Artsaema triphyltam, a higher plant, aqueous extracts of the fruit and leaf (but not of the stem) of which are effective in vitro against Escherichia coli. Only extracts of the fruit inhibit Staphylococcus aureus, and none of these extracts inhibits the spores of Neurospora crassa [1], Other extracts of this plant are reported to be ineffective against Bacillus subtilis and E. coli [ 2 | . In another series of tests aqueous extracts showed little or no inhibition of growth when tested in vitro against Staph, aureus, E. coli, Erwinia carotovora and Phytomonas tumefaciens [3], See [1] Schnell and Thayer, 1949; [2] Sanders et al., 1945; [3] Hayes, 1947. Aristolochia sp. "Dublin," a higher plant, extracts of the roots of which are effective in the treatment of experimental malaria. See Spencer et al., 1947. Aristolochia acuminata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Aristolochia arborea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aristolochia brazillensts, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aristolochia clematis, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Aristolochia cymbifera, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Aristolochia debilis, a higher plant, concentrated aqueous extracts of the Chinese d ug prepared f r o m the fruit of which are ineffective in vitro against Staphylococcus aureus and against Escherichia coli. See Gaw and Wang, 1949. Aristolochia fimbriate, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Aristolochia ornithocephala, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aristolochia saccata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aristolochia sipho, a higher plant, aqueous extracts of the leaf of which are ineffective in vitro against Staphylococcus aureus and against Escherichia coli. See Schnell and Thayer, 1949. Aristolochia triangularis, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Aristolochia tricaudata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Aristolochia trilobata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Aristotelia moqui, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947.

C r o s s r e f e r e n c e s are i n d i c a t e d by SMAIL CAPITALS

[25] Armeria formosa, a higher plant, aqueous and ether extracts of the flower, leaf, and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Armeria leacocephaia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Armeria pinifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Armeria plantagtnea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Armeria splendens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Armeria vulgaris, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Armiliaria caligata, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Armiliaria fusipes, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Armiliaria mellea, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [ 1 ], b ) to inhibit Staph, aureus but not E. coli [2], and c) to be ineffective against these two microorganisms [3, 4]. Extracts of the sporophores of this fungus are ineffective against Staph, aureus [5, 6], E. coli [5, 6], and Pseudomonas aeruginosa [6]. See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1946b; [4] Wilkins, 1947c; [5] Mathieson, 1946; [6] Wilkins and Harris, 1944d. As test o r g a n i s m in vitro, see TRICHODERMA LIGNORUM.

Armiliaria mocida, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2]. The mycelial disks, culture liquid, and extracts of the sporophores are also ineffective against these two microorganisms, and the sporophore extracts are ineffective against Pseudomonas aeruginosa as well [31. See f l ] Wilkins, 1946b; [2] Wilkins, 1947c; [3] Wilkins and Harris, 1944d. Armiliaria ramentacea, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Armiliaria robusta, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Arnebia echk>ides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Arnica chamissonis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Arnica do Campo, common name of a higher plant, extracts of which are ineffective against

ARTO CARPUS LNCISUS

experimental malaria. See Spencer et al., 1947. Arnica montana, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Aronia arbntifoUa, a higher plant, aqueous and ether extracts of the berry, leaf, and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Arrhenatheram avenaceam, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Artabotrys odoralissimus, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Artemisia absinthium, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Artemisia argentea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Artemisia dracunculoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Artemisia gnapbalodes, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Artemisia Judalca, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Artemisia maritima, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Artemisia siverslana, see PHYTONCIDES. Artemisia trldentata, a higher plant, the sage brush, extracts of which are effective in vitro against Staphylococcus aureus. Two-week-old chicks injected with the extracts, mixed with blood containing Plasmodium gallinaceum, fail to develop malaria. The extracts are also somewhat effective in the treatment of experimental malaria in chicks but are without effect in Diplococcus pneumoniae infections in mice. Doses of 0.5 to 1.0 cc injected i.p., s.c., or i.v. in chicks and mice are lethal. Smaller amounts are anesthetic [1]. Extracts of this plant are reported to be ineffective in the treatment of experimental malaria [2], See [1] Carlton et al., 1946; [2] Spencer et al., 1947. Artemisia vulgaris, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. arthritis. 1 Clinical, see PENICILLIN. 2 Rheumatoid, clinical, see AUREOMYCIN; PENICILLIN.

Arthrobotrys ollgospora, a fungus which is ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1942. arthropods, animals, extracts from whose tissues of are reported as possessing antibacterial activity. See Pavan, 1949. Artocarpus incisus, a higher plant, aqueous extracts of which are ineffective in vitro against

Cross r e f e r e n c e s a r e indicated by SMALL CAPITALS

ARUM

ESCULENTUM

[26]

Staphylococcus aureus and Escherichia coli. See O s b o m , 1943. A r u m escoleotam, a higher plant, extracts of which a r e ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See C a r d o s o and Santos, 1948. A r a m w i f i i h h i i w , a higher plant, aqueous ext r a c t s of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See O s b o r n , 1943. A r a n c n s sylvester, a higher plant, aqueous ext r a c t s of which show little or n o inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Arundinarfai falcata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See O s b o r n , 1943. A s a r a m canadense, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli [1], In another series of tests in vitro, t h e leaf, stem, and flower, and the leaf, stem, and root were f o u n d active against Staph, aureus, but inactive against E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2], See [1] O s b o m , 1943; [2] Hayes, 1947. A s a r u m canadense v. reflexnm, a higher plant (wild ginger) f r o m which two antibiotic substances have been extracted. C o m p o u n d A, the m o r e potent, is a colorless compound with t h e probable f o r m u l a C21 H u Os N-j S. Comp o u n d B is a lemon-yellow acid with the probable f o r m u l a C 1 6 H 1 1 O 7 N . Both are soluble in ethanol, acetone, c h l o r o f o r m , ethyl acetate, and dioxane, and are almost insoluble in water, benzene, and Skellysolves. Both are inactivated by cysteine. C o m p o u n d B f o r m s water-soluble salts. SPECTRUM.—Compound A. The following are inhibited by 0.0005-0.00075 m g / c c : Bacillus cereus Bacillus mycoides Clostridium botulinum Clostridium tetani Sarcina lutea T h e following are inhibited by 0.0025-0.0075 mg/cc: Bacillus subtilis Staphylococcus albus Staphylococcus aureus Streptococcus fecalis Pneumococcus, type I, is inhibited by 0.01 m g / c c . Pneumococcus, types II and III, Strep, hemolyticus and Strep, viridans, are not inhibited by 0.01 m g / c c ; Escherichia coli and paratyphi are unaffected by 0.1 Salmonella mg/cc. Bacillus cereus, B. subtilis, and Staph, albus are completely inhibited and Staph, aureus and Strep, fecalis are partially inhibited by 0.1 m g / c c of c o m p o u n d B. TOXICITY.—Intraperitoneal inj in mice of 5 m g / k g of c o m p o u n d A in sesame oil usually results in death in 2-3 days. See Cavallito and Bailey, 1946. A s a r a m europaeom, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. A s a r a m sleboldii, a higher plant, concentrated aqueous extracts of the Chinese drug prepared

f r o m the root of which are ineffective in vitro Escherichia against Staphylococcus aureus and coli. See G a w and Wang, 1949. Ascaris sols, as test organism in vitro, see GRAMICIDIN; STREPTOMYCIN.

Asclepias cornntil, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Asclepias curassavka, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli \ 11 and in vivo against experimental malaria [2]. See [1] Osborn, 1943; [ 2 ] Spencer et al., 1947. Asclepias incarnata, a higher plant, some extracts of which in vitro inhibit [ 1 ] and other extracts of which fail to inhibit [21 Staphylococcus aureus and Escherichia coli. See [11 Carlson, Douglas, and Robertson, 1948; [2] Osborn, 1943. Asclepias mexkana, a higher plant. Extracts of the stems and roots are effective in vitro against Staphylococcus aureus but not against Escherichia coli. Extracts of the leaves inhibit E. coli but not Staph, aureus. See Carlson, Douglas, and Robertson, 1948. Asclepias pulchra, a higher plant, aqueous and ether extracts of the flower, leaf, stem and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Asclepias syriaca, a higher plant, a q u e o u s extracts of the seeds and aqueous and ether extracts of the root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [ 1 | . Other aqueous extracts of this plant are reported to be ineffective against Staph, aureus and E. coli [2], In another series of tests in vitro aqueous extracts showed little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [3], See [1] Schnell and Thayer, 1949; [2] Osborn, 1943; [3] Hayes, 1947. Asclepias verticUlata, a higher plant, some extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli [1]. Other extracts are ineffective against Bacillus subtilis and E. coli [21. See [11 Carlson, Douglas, and Robertson, 1948; [2] Sanders et al., 1945. Asclepiodora viridis, a higher plant, a q u e o u s extracts of which show little or n o inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Ascochyta graminicola, a f u n g u s which in vitro inhibits the growth of Ophiobolus graminis. See Broadfoot, 1933, a and b. Ascochyta pisi, a fungus which is ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1942. Ashbya gossypii, a fungus which gives d o u b t f u l results when tested in vitro against Staphylococcus aureus and Escherichia coli. See R o b bins et al., 1945. asiatic acid, see CENTELLA ASIATICA. asiaticoside, see CENTELLA

Cross references are indicated by SMALL CAPITALS

ASIATICA.

[27] Astmbia triloba, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli [ 1 !. In another series of tests in vitro aqueous extracts showed little or no inhibition of growth against Staphylococcus aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2], See [1] Sanders et al., 1945; [21 Hayes, 1947. Asparagus officinalis, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1,2], Escherichia coli r 1, 2, 31, Bacillus subtilis [3], and Proteus X-19 [1]. Aqueous extracts of the fruit of this plant are reported to inhibit Staph, aureus but not E. coli [41. In another series of tests in vitro aqueous extracts showed little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [5]. See [11 Cardoso and Santos, 1948; [21 Osborn, 1943; [3] Sanders et al., 1945; [41 Schnell and Thayer, 1949; [5] Hayes, 1947. Asparagus sprengeri, a higher plant, aqueous extracts of the nodule of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus and the spores of Neurospora crassa. See Schnell and Thayer, 1949. aspergillic acid, a crystalline antibacterial compound obtained from the culture filtrate of the mold Aspergillus jlavus. It is extracted from the medium by adjusting to pH 4, adsorbing on charcoal, eluting with ether, evaporating, extracting with sodium bicarbonate, precipitating and reprecipitating with acid, and recrystallizing from alcohol [11. A crude product is also reported to have been isolated by extraction at pH 4 with butyl acetate, followed by shaking with sodium bicarbonate and adsorption of impurities on charcoal. The m.p. of the pure acid is 93°C. [3]. The pale cream-colored crystals are soluble in sodium bicarbonate solution, alcohol, ether, acetone, glacial acetic acid, benzene, chloroform, carbon tetrachloride, and pyridine, and are insoluble in water and petroleum ether [1]. It is optically active and remarkably resistant to heat, acid, and alkali [3], The proposed structural formula [4, 10] is as follows:

AC-CH-CH2-CH3

HC

I! CH3-CHj- C H s I CIOHIT

See G r a n d o n and King, 1949. Chlorophytum sterabergUnum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Choisya temata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. cholangitis, clinical, MYCIN. cholera, clinical, see

see

PENICILLIN;

STREPTO-

POLYPORIN.

Chondodeudron platiphyllum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Chondrilla juncea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Chorizema IlicifoUuin, a higher plant, aqueous extracts of which a r e ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Chorizia speciosa, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See C a r d o s o and Santos, 1948. Chromobacterium indicum, as test organism in vitro,

s e e KOJIC ACID.

Chromobacterium the

source

of

iodinum,

the

antibiotic

a

microorganism, IODININ.

Chromobacterium prodigiosan, a ism,

the

source

of

PRODIGIOSIN,

microorganand

an

un-

named thermostabile, water-soluble, nonpigmented substance which is antagonistic t o Bacillus subtilis, Corynebacterium diphtheriae, and Staphylococcus aureus. See Lichstein and Van de Sand, 1946. As test organism in vitro, see HIRSUTIC ACIDS; PERSOONIA PINIFOLIUS; PSALLIOTA XANTHODERMA. C h r o m o b a c t e r i u m v i o l a c e u m , 1 S e e VIOLACEIN.

As test organism in vitro, see ANTISMEGMATIS FACTOR; KOJIC ACID; CENS; SULFACTIN.

PSEUDOMONAS

FLUORES-

Chrysactina mexicana, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Chrysanthemum carinatum, a higher plant, aqueous and ether extracts of the flower, leaf, stem, and root of which are effective in vitro against the spores of Neurospora crassa, while aqueous extracts of the seed and seedling are ineffective. Only aqueous extracts of the stem and root inhibit Staphylococcus aureus, and

C r o s s r e f e r e n c e s a r e i n d i c a t e d b y SMALL CAPITALS

CHRYSANTHEMUM LEUCANTHEMUM

[74]

only aqueous extracts of the flower and root inhibit Escherichia coli. See Schnell and Thayer, 1949. Chrysanthemum leu can the mom, a higher plant, aqueous extracts of the flower, leaf, stem, and roots of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other aqueous extracts of this plant are also ineffective against Staph, aureus and E. coli [2], In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, tumeErwinia carotovora, and Phytomonas faciens [3]. See [11 Schnell and Thayer, 1949; [2] Osborn, 1943; [3] Hayes, 1947. Chrysanthemum macrophyllum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Chrysanthemum mawli, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Chrysanthemum moriflonim, a higher plant, aqueous extracts of the flower, leaf, and stem of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Chrysanthemum parthenhim, a higher plant, some extracts of which are effective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis [1] and other extracts of which are ineffective against Staph, aureus and E. coli [2], Aqueous extracts of the seed and seedling of this plant are ineffective against Staph, aureus, E. coli, and the spores of Neurospora crassa [3], See [1] Gottsnall et al., 1948; [2] Osborn, 1943; [3] Schnell and Thayer, 1949. Chrysanthemum nliginosum, - a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Chrysobalanus icaco, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Chrysogonum virginianum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Chrysophyllum cainito, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Chrysophyllum msola, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Chrysopsis mariana, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], See [1] Carlson, Douglas, and Robertson, 1948; [2] Carlson and Douglas, 1948a. chuchuasi, common name of a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Chugulraga instants, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Chugulraga leucoxylon, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947.

Clbotfcim schledel, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumejaciens. See Hayes, 1947. Cichorium endfva, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Cichorium intybus, a higher plant, some extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [2], Other extracts inhibit Bacillus subtilis and E. coli [3]. Aqueous extracts of the leaf and stem are ineffective against Staph, aureus and E. coli [4]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [5], See [1] Osborn, 1943; [2] Gottshall et al., 1949; [3] Sanders et al., 1945; [4] Schnell and Thayer, 1949; [5] Hayes, 1947. Cicnta bulbifera, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Cicuta maculata, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli [1]. In another series of tests in vitro, aqueous extracts are reported to show little or no inhibition of growth against Staphylococcus aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2]. See [1] Sanders et al., 1945; [2] Hayes, 1947. Cimicifuga racemosa, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Cinchona ledgeriana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cinchona succiruhra, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cinnamomum brevifolium, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cinnamomum burmannii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Osborn, 1943. Cinnamomum camphora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cinnamomum lourerii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cinnamomum pedunculatum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cinnamomum zeylanicum, a higher plant, aqueous extracts of which arc ineffective in vitro

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[75] against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Circaea lutetiana, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. circulin, an antibiotic substance which is more effective against gram-negative than against gram-positive organisms [ 1 ]. It is produced by a bacterium closely resembling Bacillus circulans [2]. A substance isolated from a bacterium similar to B. krzemieniewski was originally designated as circulin [3]; it is now known as polypeptin [2]. Circulin is a cyclic compound having the formula (C:WH7o of the same preparation is 23 m g / k g ; the i.v. LDr.o of a preparation containing 2,700 units/mg is 20 m g / k g [5]. Guinea pigs given 18 daily injs of 10 m g / k g of the less pure preparation show only gross loss of weight: there are no morphological changes ascribable to the antibiotic agent. Eighty percent of mice survive 14 daily s.c. injs of 33 m g / k g of pure circulin, but only 10% survive 80 m g / k g . Rats given 200 m g / k g per day orally f o r 7 days exhibit no toxic symptoms [5]. Chronic s.c. administration in mice results in sloughing of tissue at the inj site. Necrotic changes are noted in the kidneys of mice given single large s.c. doses. Chronic parenteral administration causes morphological changes in the kidney, stomach, and skeletal muscles [5]. Heart and respiration rates of anesthetized cats and dogs are unaffected by i.v. inj of 1-3 m g / k g of the pure preparation; the blood pressure is lowered to the extent of 10-20 mm. Hg for 10-30 min [5], ABSORPTION AND EXCRETION .—In dogs, peak blood concentrations of about 55

CISTUS LAURIFOLIUS units/cc and 35 units/cc are reached 1 hr after respective i.v. and i.m. administration of 5 mg kg. Single oral doses of 40 m g / k g result in blood levels of about 60 units/cc in 1-2 hr. After parenteral administration only 10% of the activity is recovered in the urine in 48 hr. Only 6% of the activity is recovered in the urine during the 80 hr following oral administration [5], N o detectable amounts are present in the blood of rats following oral administration of as much as 200 m g / k g [5]. EXPERIMENTAL CLINICAL RESULTS. — I n preliminary prophylactic trials in mice, CI. septicum spores diluted in 2.5% C a C h solution were introduced under the skin of the back and treatment was given at the same site immediately afterward and at 5 and 23 hr. Attempts are being made to establish infections with CI. welchii, CI. novyi, and CI. tetani in order to extend the comparisons [6]. See [1] Murray and Tetrault, 1948: [2] Garson et al„ 1949; [3] McLeod, 1948; [4] Peterson and Reineke, 1949; [5] Vander Brook and Richmond, 1949; [6] Bliss and Warth, 1950. See a l s o POLYPEPTIN.

Cirsium arvense, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1], Bacillus subtilis [2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [3]. See [1] Gottshall et al., 1949; [2] Sanders et al., 1945; [3] Hayes, 1947. Cirsium crinitimum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cirsium discolor, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. S>ee Sanders et al., 1945. Cirsium ianceoiatum, a higher plant, extracts of which are effective in vitro against Mycobacterium tuberculosis but not against Staphylococcus aureus and Escherichia coli. See Gottshall et al., 1949. Cirsium monspessuianum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cissampelos pareira, a higher plant, extracts of the roots of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Cistus cyprius, a higher plant, aqueous extracts of the garden hybrid of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cistus florentinus, a higher plant, aqueous extracts of the garden hybrid of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Cistus ladaniferus, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Cistus laurifolius, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943.

C r o s s r e f e r e n c e s a r e indicated by SMALL CAPITALS

CISTUS POPUI.IFOI.IUS

[76]

C h i o s popaltfolius, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osbom, 1943. Cfatns sympbyttfolhis, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osbom, 1943. Clstus symphytifolkis v. vaglnatus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. CHharexyhun barbinerve, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cttharexylmn berlandieri, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See O s b o m , 1943. Citharexylam pringlei, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. cttrinin, a yellow crystalline antibiotic, first isolated f r o m the molds Pénicillium citrinum and Aspergillus terreus [I]. It is also produced by A. Candidus [2,3,4], P. expansum [3], P. lividum [5], P. phoeo-janthinellum [5], P. implicacitreo-sulphuratum [5], P. chrzaszczi [5], P. tum [5], and the flowering plant Crotatoria crispata [3]. When purified by repeated recrystallizations f r o m hot ethanol, citrinin is colorless in sodium bicarbonate solution and has an m.p. of 170°C. [6]. The activity is unaffected by autoclaving for 30 min [4] but is destroyed by the action of cysteine [7]. The following formulae have been proposed for this antibiotic: A [1].

C2H5 I

B [8],

C [91

CHs H CHs Of these, f o r m u l a e is probably correct [15].

SPECTRUM.—The following microorganisms are inhibited in vitro by citrinin: Minimum inhibitory concentration Organism (mg/cc) 0.1 [10] Bacillus graveolens 0.008 [4], 0.032 [11], Bacillus mycoides 0.05-0.1 [10] Bacillus subtilis 0.016 [11] Escherichia coli 4.0(10] Mycobacterium phlei 0-125 £11] Mycobacterium smegma 0.25 [11] Photobacterium fischeri 0.016 [ 11 ] Pneumococcus 0.05 [10J Pseudomonas aeruginosa more than 15.0 [ 10 Salmonella paratyphi 8.0 [10 Salmonella typhi 1.0(10 Shigella flexneri 2.0-4.0 [ 10 Staphylococcus albus 0.008 [4] Staphylococcus aureus 0.016 [4,11], 0.4 [10] Streptococcus viridans 0.05 [10] Vibrio cholerae 1.0 [ 10] In addition, bacteria may become "sensitized" to citrinin. After 10 treatments with progressively smaller quantities of the antibiotic, the sensitivity of Staph, aureus is increased f r o m 0.4 m g / c c to 0.05 m g / c c . Other organisms that behave similarly are: Bacillus mycoides, E. coli, Ps. aeruginosa, Salm. typhi, Salm. paratyphi, Shig. dysenteriae, and Strep, viridans. Furthermore, treated staphylococci become more susceptible to the action of sulfadiazine [10], PHARMACOLOGY AND TOXICOLOGY. —The LD-.o for rats s.c. or i.v. is 67 mg/kg; for mice i.p. or s.c., 35 mg/kg; for guinea pigs s.c., 37 m g / k g ; and for rabbits i.v., 19 m g / k g [12]. In chronic toxicity tests rabbits survive 10 m g / k g i.v. daily for 26 days followed by 20 m g / k g daily for 26 days [13]. Rats receiving citrinin exhibit intense hyperemia of the ears and feet; this reaction develops within 30 min of administration of the agent and lasts for about 2 hr [12]. Animals given lethal doses show evidence of kidney damage, and those receiving the largest quantities have occasional small foci of myocarditis [12], Other reactions reported are hemorrhages in lungs and liver and accumulation of blood in the chest cavity at autopsy [10]. Repeated i.v. administration in rabbits reduces the amount of hemoglobin but has little or no effect on the number of erythrocytes and leucocytes. Also noted after i.v. inj in rabbits are miosis, hyperemia, salivation, increased bronchial secretion, and lacrimation, none of which is completely eradicated by atropine [12]. Lowering of body temperature is also reported [10]. Local application of 1-5% ointments or 1-20% aqueous solutions causes no irritation to skin of rabbits or humans; a 2 % solution injected i n t r a d e r m a l s has no effect in human beings but causes slight redness in rabbits. Concentrations of 0.8-2.0% are irritating to the mucous membranes of both human beings and rabbits [14], In dogs citrinin has been f o u n d to produce a temporary fall in b.p., dilatation of the blood vessels of the skin and kidneys, and increased peristalsis of the stomach and intestines [ 12]. Another investigator finds that i.v. inj of 60 m g / k g in cats and dogs results in a fall in b p. and slowing of the heart, while very slow inj

Cross references are indicated by SMALL CAPITALS

[77] of 100 mg'kg has little or no effect. Nasal instillation is without effect on b p. Administration by practically all routes results in demonstrable quantities of citrinin in the blood (14). On isolated organs, citrinin causes bronchial constriction, increased tone of cardiac muscle, frog gastrocnemius, and intestines, and decreased uterine tone. The various pharmacological effects of this agent are characterized by tachyphylaxis [12]. EXPERIMENTAL CLINICAL RESULTS. —Local application of citrinin as a powder is superior to sulfadiazine in the treatment of rabbits infected with Staph, aureus [10]. Mice weighing 18-20 gm are not cured of Siaph. aureus infections by 0.5 mg injs every 5 hr for 3 days [14]. Dramatic results have been obtained in three human cases of staphylococcal and streptococcal infections treated locally with citrinin [10]. See [1] Hetherington and Raistrick, 1931; [2] Waksman, 1944; [3] Gore et al„ 1946; [4] Timonin, 1942; [5] Pollock, 1947; [6] Bailey and Cavallito, 1943; [7] Cavallito and Bailey, 1944a; [8] Gore et al„ 1948; [9] Cartwright et al., 1949; [10] Wang et al., 1947; [11] Kavanaugh, 1947b; [12] Ambrose and De Eds, 1946; [13] Ambrose and De Eds, 1945; [14] Chu, 1946; [15] Carter and Ford, 1950. Citriobatus multiflorus, a higher plant, aqueous extracts of which are ineffective in vilro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Citrobacter spp., as test organisms in vitro, see STREPTOMYCIN.

Citromyces spp., as test organisms in vitro, see BACILLUS

sp.

Citrullus vulgaris, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Citrus bergamia, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Citrus Iimonia, a higher plant (lemon), aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Citrus medica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Citrus paradisi, a higher plant (grape fruit), aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ciadonia alpestris, a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus. See Burkholder and Evans, 1945. Ciadonia amaurocraea, a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus. See Burkholder and Evans, 1945. Ciadonia apodocarpa, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Bacillus subtilis [1, 2], and Escherichia coli [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Ciadonia atlantica, a lichen, extracts of which are effective in vitro against Bacillus subtilis [1, 2], B. cereus [2], and B. vulgatus [2], but not against Staphylococcus aureus [1, 2] and Escherichia coli (2). See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944.

CLADONIA CRYPTOCHLOROPHAEA

Cladonia bacillaris, a lichen, extracts of which are effective in vitro against Bacillus subtilis [ 1 ] but not against Staphylococcus aureus [1, 2] and Escherichia coli [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia borbonica, a lichen, extracts of which are effective in vitro against Staphylococcus aureus, Escherichia coli, and Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia boryi, a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus. See Burkholder and Evans, 1945. Cladonia brevis, a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus. See Burkholder and Evans, 1945. Cladonia caespiticia, a lichen, extracts of which are effective in vitro against Staphylococcus aureus and Bacillus subtilis [1, 2] but not against Escherichia coli [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia capitata, a lichen, extracts of which are effective in vitro against Staphylococcus aureus and Bacillus subtilis [1, 2] but not against Escherichia coli [2]. See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia caroliniana, a lichen, extracts of which are effective in vitro against Bacillus subtilis [1, 2], B. cereus [2], and B. vulgatus [2], but not against Staphylococcus aureus [1, 2] and Escherichia coli [2]. See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia cblorophaea, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia clavulifera, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Bacillus subtilis [1], and Escherichia coli [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia coniocraea, a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus [1]. Extracts of this lichen are also reported to inhibit Staph, aureus and B. subtilis but not Escherichia coli [2]. See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia conista, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Bacillus subtilis [1], and Escherichia coli [2]. See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia cristatella, a lichen, extracts of which are effective in vitro against the following: Bacillus cereus [1], B. mycoides [2], B. subtilis [1, 2], B. vulgatus [1], Diplococcus pneumoniae [2], Sorcina lutea [2], Staphylococcus albus [2], and Staph, aureus [1, 2] and ineffective against Aerobacter aerogenes [2], Alcaligenes fecalis [2], Escherichia coli [1, 2], Proteus vulgaris [2], Serratia marcescens [2], Streptococcus hemolyticus [2], and Strep, viridans [2]. See also U S N I C ACID. See [1] Burkholder et al., 1944; [2] Burkholder and Evans, 1945. Cladonia cryptochlorophaea, a lichen, extracts of which are effective in vitro against Staphylococcus aureus [1, 2] but not against Bacillus subtilis [11 and Escherichia coli [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944.

C r o s s references are indicated by SMALL CAPITALS

CLADONIA CYANIPES

[7S]

Cladonia cyanipes, a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus. See Burkholder and Evans, 1945. Cladonia deformis, a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus. See Burkholder and Evans, 1945. Cladonia delkata, a lichen, extracts of which are effective in vitro against Alcaligenes fecalis but not against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia fimbriata, a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus. See Burkholder and Evans, 1945. Cladonia furcata, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Bacillus subtilis [1], Extracts of this lichen are also reported to inhibit Staph, aureus but not B. subtilis and Escherichia coli [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia glauca, a lichen, extracts of which are effective in vitro against Alcaligenes fecalis, Staphylococcus aureus, and Bacillus subtilis [ 1 , 2 ] but not against Escherichia coli, Serratia marcescens, and Aerobacter aerogenes [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia gonecha, a lichen, extracts of which are effective in vitro against Staphylococcus aureus but not against Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia gracilis v. chordalis, a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus. See Burkholder and Evans, 1945. Cladonia gracilis v. dllatata, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia gracilis v. elongata, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia grayi, a lichen, extracts of which are effective in vitro against Staphylococcus aureus [1, 2], Bacillus cereus [2], B. subtilis [1, 2], and B. vulgatus [2] but not against Escherichia coli [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia incrassata, a lichen, extracts of which are effective in vitro against Bacillus subtilis [1, 2] but not against Staphylococcus aureus [1, 2] and Escherichia coli [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia macilenta, a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus. See Burkholder and Evans, 1945. Cladonia mateocyatha, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia merochlorophaea, a lichen, extracts of which are effective in vitro against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia mitis, a lichen, extracts of which are effective in vitro against the following: Bacillus mycoides, B. subtilis, Clostridium welchii,

Diplococcus pneumoniae, Sorcina lutea. Staphylococcus albus, Streptococcus hemolyticus, and Strep, viridans, and ineffective against Aerobacter aerogenes, Alcaligenes fecalis, Escherichia coli, Proteus vulgaris, Serratia marcescens, and Staph, aureus. See Burkholder and Evans, 1945. Cladonia nemoxyna, a lichen, extracts of which are effective in vitro against Staphylococcus aureus and Bacillus subtilis [1, 2] but not against Escherichia coli [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia ocbrochlora, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia papillaria, a lichen, extracts of which are effective in vitro against Staphylococcus aureus and Bacillus subtilis [1], Extracts of this lichen are also reported to inhibit Staph, aureus but not B. subtilis [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia pityrea, a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus. See Burkholder and Evans, 1945. Cladonia pleurota, a lichen, extracts of which are effective in vitro against the following: Bacillus mycoides, B. subtilis, Clostridium welchii, Diplococcus pneumoniae. Sorcina lutea, Staphylococcus albus, Streptococcus hemolyticus, and Strep, viridans [1], and ineffective against Aerobacter aerogenes [1], Alcaligenes fecalis [1], Escherichia coli [1, 2], Proteus vulgaris [1], Serratia marcescens [1], and Staph, aureus [1, 2]. See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia pyxldata, a lichen, extracts of which are effective in vitro against Staphylococcus aureus [1, 2] and Bacillus subtilis [1] but not against Escherichia coli [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia rangiferina, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Bacillus subtilis [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens [2]. See [1] Burkholder and Evans, 1945; [2] Hayes, 1947. Cladonia robbinsii, a lichen, extracts of which are effective in vitro against Bacillus subtilis [1] but not against Staphylococcus aureus [1, 2] and Escherichia coli [2], See [11 Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia santensis, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia scabriuscola, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia squamosa, a lichen, extracts of which are effective in vitro against Staphylococcus aureus and Bacillus subtilis [1, 2] but not against Escherichia coli [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia squamosa v. denticollis, a lichen, extracts of which are ineffective in vitro against

Cross references are indicated by

SMALL

CAPITALS

[79] Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia strepsilis, a lichen, extracts of which are effective in vitro against Staphylococcus aureus and Bacillus subtilis [I. 21 but not against Escherichia coli [2]. See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia subcariosa, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus [I, 2], Bacillus subtilis [1, 2], and Escherichia coli [2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia submitis, a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus [11. Extracts of this lichen are also reported to be ineffective against B. subtilis, Escherichia coli, and Staph, aureus [2]. See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia sobtenuis, a lichen, extracts of which are effective in vitro against Bacillus subtilis [1, 2] but not against Staphylococcus aureus [1, 2] and Escherichia coli [2J. See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia sylvatica, a lichen, extracts of which are effective in vitro against the following: Bacillus mycoidcs, B. subtilis, Diplococcus pneumoniae, Sarcina lutea, and Staphylococcus albus, and ineffective against Aerobacter aerogenes, Alcaligenes fecalis, Escherichia coli, Proteus vulgaris, Serratia marcescens, Staph, aureus. Streptococcus hemolyticus, and Strep, viridans. See Burkholder and Evans, 1945. See also

USNIC

ACID.

Cladonia túrgida, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Cladonia uncialis, a lichen, extracts of which are effective in vitro against the following: Bacillus mycoides [1], B. subtilis (1, 2], Diplococcus pneumoniae [1], Sarcina lutea [1], Staphylococcus albus [1], Streptococcus hemolyticus [1], and Strep, viridans [1], and ineffective against Aerobacter aerogenes [1], Alcaligenes fecalis [1], Escherichia coli [1, 2], Proteus vulgaris [1], Serratia marcescens [1], and Staph, aureus [1, 2], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladonia verticillata, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Bacillus subtilis [1], and Escherichia coli (2]. See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Cladosporiuin fulvura, a fungus which is ineffective in vitro against Staphylococcus aureus, Salmonella typhi, and Endomycopsis albicans. The culture media of this fungus are ineffective against Staph, aureus and Botrytis allii. See Brian and Hemming, 1947. Cladosporium herbarum, a fungus which is ineffective in vitro against Staphylococcus aureus [1, 21, Salmonella typhi [1], Endomycopsis albicans [1], Escherichia coli 12], and Pseudomonas aeruginosa [2], The culture media of this f u n g u s are also ineffective against Staph, aureus and Botrytis allii [1]. In other tests in vitro the fungus is reported as effective against the growth of C. herbarum and weakly effective against the growth of Ophiobolus graminis [3]. See [1] Brian and Hemming, 1947; [2] Wilkins and Harris, 1942; [3] Brömmelhues, 1935. For further reference, see Johns, 1947, unpublished. As test organism in

CLAVACIN vitro, s e e ASPERGILLIC ACID; B E R B E R I N E ; C H E I R O L I N E ; CLAVAC1N; M Y C O P H E N O L I C ACID; P E N I C I L LIC ACID; P I N O S Y L V I N E ; P R O A C T I N O M Y C I N ; T R I C H OTHECIN; TYROTHRICIN.

Clarkia elegans, a higher plant, aqueous extracts of the seed and seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other aqueous extracts of this plant inhibit Staph, aureus but not E. coli [2). See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Claudopus nidulans, a fungus which is reported by various investigators a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], b ) to inhibit Staph, aureus but not E. coli [3], and c) to be ineffective against these microorganisms [4], See [1] Hervey, 1947; [2] Wilkins, 1947b; [3] R o b b i n s et al., 1945; [4] Wilkins, 1947c. Claudopus variabilis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clausena wampii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. clavacin, a crystalline antibiotic (also k n o w n as claviformin, clavatin, expansin, patulin, and penicidin) which is obtained f r o m the culture media of the following f u n g i : Aspergillus clavatus [1] Aspergillus giganteus [2] Aspergillus terreus [2] Gymnoascus sp. [3] Pénicillium spp. [3, 7] Pénicillium claviforme [4] Pénicillium divergens [5] Pénicillium equinum [6] Pénicillium expansum [2] Pénicillium leucopus [7] Pénicillium melinii [2] Pénicillium novae zeelandiae [6] Pénicillium patulum [2] Pénicillium urticae [2] One method of obtaining this agent f r o m the culture m e d i u m is by adsorbing on Norit and eluting with ether and c h l o r o f o r m [8]. It may be purified by fractionation on a Permutit column, elution with chloroform, evaporation, and crystallization by refrigeration [9]. T h e crystals are colorless prisms [9]; the m.p. is reported variously to be 1 1 0 ' C . [4], 109°-110° C. [9] and 111°C. [10]. The structural f o r m u l a is probably [20]: -C = O I |

oI C Hcf HsC

V

X

C = CH CHOH

It is soluble in ether, chloroform, ethanol, water [1], and acetone [4] and insoluble in benzene and petroleum ether [4], Alkalis destroy the activity of clavacin, but boiling f o r 30 min in N / 1 0 hydrochloric acid is without effect [4]. T h e activity is inhibited by s e r u m [4] and cysteine [11].

Cross references are indicated by SMALL CAPITALS

[80]

CLAVACIN

SPECTRUM—Clavacin inhibits the following microorganisms in vitro in the concentrations s h o w n : Inhibitory concentration Organism 1:160,000 [19 Actinomyces scabies 1:50,000 [8 Aerobacter aerogenes 1:125,000 [8 Bacillus cereus 1:100,000 [8 Bacillus megatherium 16 m i c r o g r a m s / c c [12] Bacillus mycoides 1:200,000 [8 4 m i c r o g r a m s / c c [12] Bacillus subtilis 1:200,000 [8 Escherichia coli 1:80,000 [4], 1:100,000 [8] 1:33,000 [10], 8 m i c r o g r a m s / c c [12 Klebsiella pneumoniae 8 m i c r o g r a m s / c c [12 Mycobacterium phlei 16 m i c r o g r a m s / c c [12 Mycobacterium smegma 1 m i c r o g r a m / c c [12 Neisseria catarrhalis 1:80,000 [10 Photobacterium

ftscheri

0.25 m i c r o g r a m s / c c [12P rot eus vulgaris 1:3 3,000 [ 10 Pseudomonas aeruginosa 1:40,000 [4] 125 m i c r o g r a m s / c c [12 Salmonella breslau 1:75,000 [8 Salmonella choleraesuis 1:150,000 [8 Salmonella enteritidis 1:80,000 [4 Salmonella paratyphi 1:80,000 [ 10 Salmonella schottmuelleri 1:60,000 [8] 1:33,000-1:50,000 [10 Salmonella typhi 1:160,000 [4], 1:50,000 [10 Sarcina lutea 1:500,000 [8 Shigella flexneri 1:80,000 [ 10 Shigella shigae 1:50,000 [ 10 Staphylococcus aureus 1:60,000 [4] 1:60,000-1:200,000 [8 1:50,000 [10], 8 m i c r o g r a m s / c c [12 Streptococcus pneumoniae 1:80,000 [10 Streptococcus pyogenes 1:40,000 [4] 1:33,000-1:80,000 [10 Streptococcus viridans 1:33,000 [10

T h e following d a t a have b e e n r e p o r t e d reg a r d i n g t h e activity of clavacin against saprop h y t i c f u n g i [13]: Fungus Activity Aspergillus clavatus Dematium sp. Fusarium sp. Pénicillium luteum-purpurogenum

in u n i t s / g m 3,000 15,000 25,000 25,000

T h e f o l l o w i n g p a t h o g e n i c f u n g i are affected by clavacin as follows: Inhibitory concentration Fungus 1:160,000 [14] Achorion gallinae 1:10,000 [14] Achorion gypseum 1:160,000 [14] Achorion quinckeanum 1:80,000 [14] Achorion violaceum 1:11,000 [14] Bodinea violacea 1:160,000(14] Endodermophyton indicum 1:160,000 [14] Endodermophyton tropicale n o inhibition at Endomycopsis albicans 1:11,000 [14] 1:160,000 [14] Epidermophyton cruris 1:40,000 [14] Epidermophyton perneti 1:80,000 [14] Epidermophyton rubrum 1:160,000 [14] Grubyella schoenleinii 1:11,000(14] Microsporum equinum 1:11,000 [14] Microsporum ferrugineum 1:11,000 [14] Microsporum julvum 1:10,000 [14] Microsporum japonicum Monilia albicans 1:2.500 (partial i n h i b i t i o n ) [15]

Fungus Oidium asteroides Sabouraudites Sabouraudites Sabouraudites

audouini felineus lanosus

Trichophyton Trichophyton Trichophyton Trichophyton Trichophyton Trichophyton Trichophyton

album asteroides balcaneum cerebriforme decalvans depressum discoides

Trichophyton Trichophyton Trichophyton Trichophyton Trichophyton Trichophyton

equinum jumatum granulosum gypseum lacticolor louisianicum

Trichophyton Trichophyton Trichophyton Trichophyton Trichophyton

persicolor plicatile sabouraudii sulphureum tonsurans

Inhibitory concentration 1:2,500 ( p a r t i a l i n h i b i t i o n ) [15] 1:11,000 [14] 1:11,000 [14] n o inhibition at 1:11,000(14] 1:11,000 [14] 1:11,000 [14] 1:160,000 [14] 1:11,000 [14] 1:80,000 [14] 1:10,000 [14] n o inhibition at 1:11,000 [14] 1:11,000(14] 1:80,000 [14] 1:11,000 [14] 1:10,000 [15 1:20,000(14] n o inhibition at 1:11,000 [14] 1:160,000 [14] 1:10,000 [14] 1:11,000 [14] 1:20,000 [14] n o inhibition at 1:11,000 [14]

I n addition, p a r a m e c i a are killed by dilutions of 1:1,000,000 [9]. P h a g e s in bacteriaf r e e filtrates are inactivated by clavacin [16]. T e t a n u s toxin i n c u b a t e d with clavacin and injected into mice fails to cause d e a t h (17], Isoclavacin, dimethyl isoclavacin, a n d y-keto/3(/8-G-dimethylacryl) b u t y r o l a c t o n e , all derivatives of clavacin, d o not have this effect o n t e t a n u s toxin [17], In a n o t h e r series of tests in vitro it is rep o r t e d t h a t clavacin ( c l a v i f o r m i n , o b t a i n e d f r o m Pénicillium claviforme), completely inhibits the g r o w t h in vitro of t h e following o r g a n i s m s in the c o n c e n t r a t i o n s s h o w n : Concentration Organism Actinomyces scabies 1:160,000 Bacillus polymyxa 1:80.000 Bacillus subtilis 1:80,000 Bacterium aroidae 1:160,000 Bacterium carotovorum 1:320,000 Bacterium tumefaciens 1:160,000 Claviceps purpurea 1:80,000 Corynebacteritim michiganense 1:20,000 Corynebactcrium sepedonicum 1:80,000 Gloeosporium musarum 1:5,000 Leuconostoc sp. 1:160,000 PeniciHium digitatum 1:5,000 Phytophthora erythroseptica 1:320,000 Pseudomonas inarginalis 1:40,000 Pseudomonas syringae 1:20,000 Pythium ultimum 1:800,000 Rhizoctonia crocorum 1:5,000 Rhizoctonia solani 1:20,000 Sclerotinia sclerotiorum 1:5,000 Stereum purpureum 1:2D,000 Vcrticillium dahliae 1:5,000 Xanthomonas begoniae 1:160,000 Xanthomonas campestris 1:160,000 Xanthomonas malvacearum 1:320,000 It is ineffective in vitro against Botrytis cinerea. T h e following are partially inhibited in vitro in c o n c e n t r a t i o n s of a b o u t 1:5,000: Alternaria citri, Bvssochlamys fulva, Cladosporium

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[81] herbarum, Fusarium avenaceum, F. Myrothecium roridum, Penicillium Trichotliecium roseum [19].

culmorum, expansum,

TOXICITY AX D PHARMACOLOGY.— T h e i.p. M T D of a crude preparation is 3.5 m g / k g f o r mice [18]. Death results within a few hours a f t e r i.v. inj of 0.5 mg in 20 gm mice; 2.5 mg p.o. and 2 mg s.c. also are lethal [4], Eighty-five percent mortality within three days after i.v. administration of 1.0 mg in 29 gm mice and 100% mortality after 1.5 mg are also reported [10], I.v. inj of 7.5 mg in cats causes a sharp rise in b p., followed by a fall considerably below the initial level [4]. CLINICAL RESULTS.—Solutions of 1:5,000 —1:20,000 applied locally to the nasal passages and the nasopharynx, although tolerated without ill effect, are largely unsuccessful in the treatment of the common cold [10]. See [1] W a k s m a n et al„ 1942; [2] Kent and Heatley, 1945; [3] Karow and Foster, 1944; [4] Chain, Florey, Jennings, and Callow, 1943; [5] Barta and Mecir, 1948; [6] Burton, 1949; [7] Umezawa, Mizuhara, Üekane, and Hagiwara, 1948; [8] Waksman et al., 1943; [9] K a t z m a n et al., 1944; [10] Raistrick et al., 1943; [11] Cavallito and Bailey, 1944a; [12] Kavanaugh, 1947b; [13] Reilly et al, 1945; [14] Sanders, 1946; [15] Herrick, 1945; [16] Jones, 1945; [17] Puetzer and G r u b b , 1946; [18] Waksman, 1945; [19] Gilliver, 1946; [20] Carter and F o r d , 1950. See also P E N I C I L L I U M CLAVIFORME; LIUM NOVAE

PENICLLIIUM ZEELANDIAE.

EQUINUM;

PENICIL-

Clavaria sp., a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Clavaria argillacea, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria australiana, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Clavaria botrytis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [1,2], Escherichia coli [1,2], and Pseudomonas aeruginosa [1], See [1] Wilkins and Harris, 1944d; [2] Mathieson, 1946. Clavaria cinerea, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria comiculata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria corniculata v. pratensis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria cristata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escheraeruginosa ichia coli [I, 2], and Pseudomonas [11 See [1] Wilkins and Harris, 1944d; [2] Mathieson, 1946.

CLAVARIA

SINAPICOLOR

Clavaria cristata cinerea, a f u n g u s , extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Clavaria flaccida, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria flava, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Clavaria formosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [1,2], Escherichia coli [1, 2], and Pseudomonas aeruginosa [1]. See [1] Wilkins and Harris, 1944d; [2] Mathieson, 1946. Clavaria fragUis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria fumosa, a f u n g u s , extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria fusiformis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria gracilis, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Clavaria inaequalis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria kunzei, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria ochraceo-salmonicolor, a f u n g u s , extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Clavaria persimilis, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria pistlllaris, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria pyxidata, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Clavaria rugosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria sinapkolor, a f u n g u s , extracts of the sporophores of which are ineffective in vitro

Cross references are indicated by SMALL CAPITALS

[82]

CLAVARIA STRICTA

against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Clavaria stricta, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria ombrinella, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Clavaria vennknlarls, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clavaria versa tills, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. c l a v a d n , see CLAVACIN.

Claviceps purpurea, a fungus which gives doubtful results when tested in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. As test organism in vitro, s e e ASPERGILLIC ACID; BERBERINE; CHEIROLINE; CLAVACIN; OLIOTOXIN; MYCOPHENOLIC ACID; PROACTINOMYCIN; SPIRAEA.

c l a v i f o r m i n , see CLAVACIN.

Claytonla perfoliata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. CleistophoUs patens, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Clematis armandii, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clematis caracasana, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Clematis fremontli, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clematis heracleaefolhim, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clematis heracleaefolhim v. davidiana, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clematis integrifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clematis paniculata, a higher plant, aqueous extracts of the seed of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora erassa. See Schnell and Thayer, 1949. Clematis recta, a higher plant, aqueous extracts of the seeds of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clematis stans, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clematis texensis, a higher plant, aqueous extracts of which are effective in vitro against

Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clematis vitalba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clematis viticella v. kermensina, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cleome gynandra, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cleome spinosa, a higher plant, aqueous extracts of the seed and flower of which are effective in vitro against the spores of Neurospora crassa; aqueous extracts of the seedling, leaf, stem, and root are ineffective. Only extracts of the flower inhibit Staphylococcus aureus. None of these extracts inhibits Escherichia coli [1], Other aqueous extracts of this plant are ineffective against Staph, aureus and E. coli [2], See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Clerodendron, a higher plant (Chinese glorybower), ether extracts of the leaf of which are effective in vitro against Staphylococcus aureus but not Escherichia coli and the spores of Neurospora crassa. Aqueous extracts of the leaf and both aqueous and ether extracts of the berry are ineffective against these three organisms. See Schnell and Thayer, 1949. Clerodendron bakeri, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clerodendron colebrookianum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clerodendron disparifolium, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clerodendron fallax, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clerodendron foetidum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clerodendron fragrans, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clerodendron fragrans v. pleniflorum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Clerodendron heterophyllum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Clerodendron myricoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbern, 1943. Clerodendron nutans, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clerodendron siphonanthus, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Clerodendron splendens, a higher plant, aqueous extracts of which are ineffective in vitro

C r o s s r e f e r e n c e s are indicated b y SMALL CAPITALS

[83] against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clerodendron thomsonae, a higher plant, aqueous extracts of which are ineffective in vino against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clerodendron trichotomum, a h i g h e r p l a n t , aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and in vivo against experimental malaria [2], See [1] Osborn, 1943; [2] Spencer et al., 1947. Clerodendron umbellatum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clethra alnifolia, a higher plant, aqueous extracts of the fruit of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Clethra arborea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cleyera fortune!, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Cleyera ochnacea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cllanthus punlceus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clinopodium nepeta, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Clinopodium vulgare, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clltocybe aggregate, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clltocybe aurantiaca, a fungus which is effective in vitro against Staphylococcus aureus a n d / o r Escherichia coli [1,2]. Extracts of the sporophores of this fungus inhibit E. coli but not Staph, aureus and Pseudomonas aeruginosa 31. The culture liquid [3,4] and mycelial disks 3] inhibit Staph, aureus but not E. coli. See 1] Wilkins, 1946b; [2] Wilkins, 1947b; [3] Wilkins and Harris, 1944d; [4] Wilkins, 1947c. Clltocybe australiana, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Clltocybe brumalis, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clltocybe candicans, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clltocybe cartilaginea, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli,

CLITOCYBE G A N G R A E N O S A

and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clitocybe cerussata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clltocybe clavipes, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. The culture liquid and mycelial disks of this fungus inhibit Staph, aureus but not E. coli. See Wilkins and Harris, 1944d. Clitocybe connata, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clltocybe cyathiformis, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa [1]. The culture media of this fungus are weakly inhibitory for Staph, aureus a n d / o r E. coli [2], See [1] Wilkins and Harris, 1944d; [2] Wilkins, 1947c. Clltocybe dealbata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clltocybe diatreta, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clitocybe ditopa, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores of this fungus inhibit Staph, aureus and E. coli but not Pseudomonas aeruginosa L2J. See [1] Hervey, 1947; [2] Wilkins and H a r n s , 1944d. Clltocybe flaccida, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa [1]. The culture media of this fungus inhibit Staph, aureus but not E. coli [2J. See [1] Wilkins and Harris, 1944d; [2] Wilkins, 1947c. Clitocybe flaccida v. lobata, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus, and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clitocybe fragrans, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa [1]. The culture media of this fungus inhibit Staph, aureus and E. coli [2], See [1] Wilkins and Harris, 1944d; [2] Wilkins, 1947c. Clitocybe gallinacea, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus inhibit Staph, aureus but not E. coli and Pseudomonas aeruginosa [2], See [1] Wilkins, 1947c; [2] Wilkins and Harris, 1944d. Clltocybe gangraenosa, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d.

Cross references are indicated by SMALL CAPITALS

CLITOCYBE CEOTROPA

[84]

CUtocybe geotropa, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2]. See [1] Hervey, 1947; [2] Wilkins and Harris, 1944d. CUtocybe gigantea v. Candida, a fungus which produces the group of antibiotic substances known

as

CLITOCYBINES.

CUtocybe gilva, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. CUtocybe hirneola, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa [1], The culture media of this fungus inhibit Staph, aureus but not E. coli [2]. See [1] Wilkins and Harris, 1944d; [2] Wilkins, 1947c. CUtocybe ttlndens, a fungus which is reported by various investigators a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2] and b) to be inhibitory for these microorganisms [3]. See [1] Wilkins, 1947c; [2] Hervey, 1947; [3] Robbins et al., 1945. CUtocybe infundibuliformis, a fungus, extracts of the sporophores of which are reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa [1] and b) to be ineffective against Staph, aureus and E. coli [2], The fungus is weakly inhibitory for Staph, aureus and/or E. coli [3]. See [1] Wilkins and Harris, 1944d; [2] Mathieson, 1946; [3] Wilkins, 1947b. CUtocybe inornata, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. CUtocybe inversa, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Mycelial disks and culture liquid of this fungus inhibit Staph, aureus and E. coli. See Wilkins and Harris, 1944d. CUtocybe investiens, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Robbins et al., 1945. Clitocybe maxima, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clitocybe metachroa, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clitocybe nebularis, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores of this fungus are ineffective against Staph, aureus [2, 3], E. coli [2, 3], and Pseudomonas aeruginosa [2]. The culture media and m y c e l i a l disks are also ineffective against Staph, aureus and E. coli [2J. See [1] Wilkins, 1947c; [2] Wilkins and Harris, 1944d; [3] Mathieson, 1946.

CUtocybe obsoleta, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [ 1 ]. Extracts of the sporophores of this fungus also inhibit Staph, aureus and E. coli but not Pseudomonas aeruginosa [2], The culture media inhibit Staph, aureus at 1:128 [1], See [1] Hervey, 1947; [2] Wilkins and Harris, 1944d. Clitocybe odora, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clitocybe olearia, a fungus, the culture media of which are weakly inhibitory in vitro for Staphvlococcus aureus and/or Escherichia coli. See Wilkins, 1947c. Clitocybe paraditopa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Clitocybe pascua, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Clitocybe phyllophila, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [ 1 ]. Extracts of the sporophores of this fungus are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Hervey, 1947; [2] Wilkins and Harris, 1944d. CUtocybe pruinosa, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clitocybe rivulosa, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [ 1 ]. Extracts of the sporophores of this fungus inhibit Staph, aureus and E. coli [2], See [1] Wilkins, 1947c; [2] Wilkins, 1946a. Clitocybe robusta, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. It is also reported to inhibit Staph, aureus and/or E. coli [2], See [1] Hervey, 1947; [2] Wilkins, 1947b. Clitocybe tabescens, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1,2,3] and b) to be inhibitory for Staph, aureus but not for E. coli [4], See [1] Wilkins, 1947c; [2] Hervey, 1947; [3] Wilkins, 1947b; [4] Robbins et al., 1945. Clitocybe velutipes, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Clitocybe verbecina, a fungus, extracts of the sporophores of which are effective in viiro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clitocybe vermicularis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. clitocybines, a group of antibiotic substances produced by the fungus Clitocybe giganlea v. Candida [1,2]. Clitocybine B is the only one effective against Mycobacterium tuberculosis and apparently occurs in the culture medium; the other clitocybines occur in the mycelium and inhibit other microorganisms [2]. The clit-

Cross references are indicated by

SMALL CAPITALS

[85] ocybines are soluble in chloroform, water, acetone, amyl acctate. and sulphuric ether. They are stable at 40 -50 C. and are destroyed at 7 0 ° - 8 0 ' C . [1], SPECTRUM.—The following microorganisms are inhibited by the clitocybines (except clitocybine B) [1]: Brucella abortus Escherichia coli Pseudomonas aeruginosa typhi Salmonella Staphylococci One cc of an aqueous suspension containing 0.1 gm dried fungus is lethal for a 300 gm guinea pig on s.c. inj. Sulphuric ether extracts are tolerated in larger doses [ 1 ]. Guinea pigs injected with mixtures of clitocybine B and Myco, tuberculosis do not develop pathological lesions. See [1] Hollande, 1945; [2] Hollande, 1947. Clitopilus abortivus, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1], The culture media of this f u n g u s are weakly inhibitory for Staph, aureus a n d / o r E. coli [2], See [1] Hervey, 1947; [2] Wilkins, 1947a. Clitopilus prunulus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Clitopilus subfrumentaceus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Clitoris ternata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cllvia miniata, a higher plant, aqueous extracts of the garden hybrid of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clostridium spp. 1 As test organism in vitro, s e e ANTISMEGMATIS FACTOR; GRAMICIDIN; N I S I N ;

TYROCIDINE. 2 Experimental i n f e c t i o n s , see PENICILLIN.

Clostridium aerofeoetidum, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. Clostridium bifermentans, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. As test organi s m in

vitro,

s e e ASPERGILLIC ACID.

Clostridium botulinum, as test organism in vitro. s e e A R C T I U M M I N U S AND O N O P O R D O N T A I R I C U M ; A S A R U M CANADENSE V. R E F L E X U M ; BACILLUS s p . ; K O J I C ACID; LEPTOTAENIA DISSECTA; PERSOONIA PINIFOLIUS; PSALLIOTA XANTHODERMA; R H U S HIRTA.

Clostridium botulinum type A, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. Clostridium botulinum type B, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished.

CLOSTRIDIUM

OEDEMATIENS

Clostridium butyricum, a microorganism which in vitro inhibits the growth of Ophiobolus graminis [1]. Extracts are ineffective in vitro against Staphylococcus aureus and Escherichia coli, but show d o u b t f u l traces of inhibition against Corynebacterium xerosis in some tests [2], See [1] Broadfoot, 1933a and b; [2] Jennings and Lancaster, 1945, unpublished. As test organism in vitro, see CHAETOMIN; STREPTOTHRICIN.

Clostridium butyricum (Bacillus pasteurianum), a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. Clostridium butyricum (Bacillus pectinovorus), a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. Clostridium centrosporogenes, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. Clostridium chauvoei, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. As test organism in vitro, s e e BACILLUS

sp.

Clostridium fallax, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. As test organism in vitro,

see

POLYPEPTIN;

SUBTENOLIN.

Clostridium felsineus, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. Clostridium feseri, as test organism in vitro, see

CHLORAMPHENICOL.

Clostridium hlstolyticum, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. As test organism in vitro, s e e ASPERGILLIC ACID; BACITRACIN; CHLORAMPHENICOL; GRAMICIDIN S ; K O J I C ACID; LEPTOTAENIA DISSECTA; P E N A T I N ; P O L Y P E P T I N ; P R O T O A N E M O N I N ; R H U S HIRTA; S U B T E N O L I N .

Clostridium multifermentans tenalbum, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. Clostridium novyi, as test organism in vitro, s e e ASPERGILLIC ACID; AYFIVIN; BACILLUS s p . ; BACITRACIN; CHLORAMPHENICOL; KOJIC ACID; P R O T O A N E M O N I N ; STREPTOTHRICIN; S U B T E N OLIN.

Clostridium oedematiens, a microorganism, extracts of which are ineffective in vitro against Escherichia coli and Corynebacterium xerosis, but show d o u b t f u l traces of inhibition against Staphylococcus aureus in some tests. See Jennings and Lancaster, 1945, unpublished. As test organism in vitro, see ARCTIUM MINUS AND ONOPORDON T A U R I C U M ; AYFAVIN; F U M I G A C I N ; PENICILLIN; P R O T O A N E M O N I N ; SUBTILYSINE.

Clostridium oedematiens malign], as test organism in vitro, see SUBTENOLIN.

Cross references are indicated by SMALL CAPITALS

CLOSTRIDIUM PARASPOROGENES

[86]

Clostridium parasporogenes, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. Clostridium perfrtagens. 1 As test organism in vitro, see ANACARDIC ACID; A R C T I U M M I N U S AND O N O P O R D O N T A U R I C U M ; ASPERGILLIC ACID; C E N TAUREA M A C U L O S A ; C H L O R A M P H E N I C O L ; EPID E R M O P H Y T O N F L O C C O S U M ; K O J I C ACID; L E P T O TAENIA DISSECTA; MICROSPORUM AUDOUINI; NEOMYCIN; PENICILLIN; P O L Y P E P T I N ; RHUS HIRTA; S U B T E N O L I N ; T R I C H O P H Y T O N MENTAGROPHYTES; TRICHOPHYTON RUBRUM; TRICHOPHYTON TONSURANS; T R I C H O P H Y T O N VIOLACEUM. 2 Experimental infections, see P E N I C I L L I N .

Clostridium putrificum, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. As test organism in vitro, see K O J I C ACID; L E P T O T A E N I A DISSECTA; RHUS

HIRTA.

Clostridium septicum, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. 1 As test organism in vitro, s e e ANACARDIC ACID; A R C T I U M M I N U S AND O N O PORDON TAURICUM; ASPERGILLIC ACID; AUREO M Y C I N ; A Y F I V I N ; BACITRACIN; C H L O R A M P H E N ICOL; F U M I G A C I N ; P E N I C I L L I N ; PERSOONIA PINIFOLIUS; PSALLIOTA XANTHODERMA; STREPTOS U B T I L Y S I N E ; T E R R A M Y C I N . 2 Experimental infections, see BACITRACIN; N I S I N . Clostridium sordellil, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster. 1945, unpublished. As test organism in vitro, THRICIN;

s e e BACITRACIN;

STREPTOTHRICIN.

Clostridium sphenoides, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. Clostridium sporogenes, a microorganism, extracts of which are ineffective in vitro against Escherichia coli and Corynebacterium xerosis, but show doubtful traces of inhibition against Staphylococcus aureus in some tests. See Jennings and Lancaster, 1945, unpublished. As test organism in vitro, see ASPERGILLIC ACID; B A C I T R A C I N ; K O J I C ACID; L E P T O T A E N I A DISSECTA; MICROCOCCIN; PERSOONIA PINIFOLIUS; PROTOA N E M O N I N ; PSALLIOTA XANTHODERMA; R A N U N C U L U S O C C I D E N T A L S ; R H U S HIRTA.

Clostridium tertium, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. As test organism in vitro,

NEMONIN; THRICIN.

PSALLIOTA

XANTHODERMA;

STREPTO-

Clostridium tetanomorphum, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. Clostridium welchii, a microorganism, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Corynebacterium xerosis. See Jennings and Lancaster, 1945, unpublished. 1 As test organism in vitro, s e e ACTINOMYCIN; ASPERGILLIN; AYFIVIN; BACILL U S s p . ; BACITRACIN; C L A D O N I A M I T I S ; CLADONIA PLEUROTA; DICOUMARIN; FUMIGACIN; GRAMICIDIN S ; J A V A N I C I N ; M I C R O C O C C I N ; P E N I CILLIN; POLYMYXINS; PROTOANEMONIN; STREPT O T H R I C I N . 2 Experimental infections, see BACITRACIN; G R A M I C I D I N S .

Clusia fluminensis, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Clusia grandiflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Clytostoma callistegioides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cneoridium dumosum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cneorum pulverulentum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cneorum tricoccum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cnicus benedictus, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cobaea scandens, a higher plant, aqueous and ether extracts of the flowers of which are effective in vitro against the spores of Neurospora crassa, while aqueous extracts of the seed and seedling and both aqueous and ether extracts of the leaf, stem, and root are ineffective. None of these extracts inhibits Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. coccidioidal pneumonia, clinical, see A U R E O M Y CIN.

Coccidioides immitls, as test organism in vitro, s e e ACTIDIONE; A N T I B I O T I C 1 3 6 ; A U R E O M Y C I N ; BACILLOMYCIN; CHLORAMPHENICOL; LEPTOTAENIA DISSECTA; N E O M Y C I N ; P H T H I O C O L ; P L U M B A G O L ; POLYMYXIN B ; PRODIGIOSIN; PROTOANEMONIN. coccidioidosis, clinical, see P E N I C I L L I N ; S T R E P TOMYCIN.

SUBTENOLIN.

Coccobacillus spp., as test organisms in vitro,

A R C T I U M M I N U S AND O N O P O R D O N T A U R I C U M ; A S A R U M CANADENSE v . R E F L E X U M ; BACILLUS s p . ; B A C I T R A C I N ; C H L O R A M P H E N I C O L ; K O J I C ACID; PENICILLIN; PERSOONIA PINIFOLIUS; PROTOA-

Cocculus diversifolius, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cocculus laurifolius, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cocculus longifolius, a higher plant, aqueous extracts of which are ineffective in vitro against

see

POLYPEPTIN;

Clostridium tetani, a microorganism, extracts of which are ineffective in vitro against Escherichia coli and Corynebacterium xerosis, but show doubtful traces of inhibition against Staphylococcus aureus in some tests. See Jennings and Lancaster, 1945, unpublished. As test organism in vitro, see ANACARDIC ACID;

see

STREPTOMYCES

Cross references aie indicated by

AUREOFACIENS.

SMALL CAPITALS

[87] Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cocculus trilobus, see T R I L O B I N . Cochlearia officinalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Cocos nucifera, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19 [1] and in vivo against experimental malaria [2], See [1J Cardoso and Santos, 1948; [2] Spencer et al., 1947. Codiaeum pictum, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Coffea arabica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coffea excelsa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coffea liberica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coffea robusta, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coffea robusta v. quillou, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coffea zanguebariae, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cola acuminata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cola gabonensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Colchicum autumnale, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [2]. See [1] Osborn, 1943; [2] Gottshall et al., 1949. Colchicum bormuelleri, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Colchicum speciosum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. cold, common, see CI.AVACIN; P E N I C I L L I N ; S T R E P TOMYCIN.

Coleus blumei, a higher plant, aqueous extracts of the seedling, flower, and leaf, and ether extracts of the flower and leaf of which are effective in vitro against the spores of Neurospora crassa, while aqueous extracts of the stem and root are ineffective. Staphylococcus aureus is inhibited by all these extracts except aqueous extracts of the seedling, flower, stem, and root. Escherichia coli is not inhibited by any of these extracts [1]. Various other ex-

COLICINE

tracts of this plant are reported to inhibit Staph, aureus [2, 3] and Mycobacterium tuberculosis [2] but not E. coli [2, 3], See [1] Schnell and Thayer, 1949; [2] Gottshall et a l , 1949; [3] Osborn, 1943. Coleus comosus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coleus mahonii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coleus thjrsoideus, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Coli-aerogenes. 1 As test organisms in vitro, see P O L Y M Y X I N S ; 2 Clinical infections, see A U R E OMYCIN.

colicine, an antibiotic derived from a strain of Escherichia coli isolated from cat feces. It is most active against other strains of E. coli; its inhibitory action on other microorganisms may be due to the production of hydrogen peroxide. Vigorous aeration of the medium is necessary for the production of colicine. Crude colicine is obtained from the medium by adsorption on charcoal, elution with water, boiling in 80% ethanol, drying, taking up the residue in glacial acetic acid, concentrating by vacuum distillation, and precipitating with absolute ethanol. The yield is a dirty-white, nonhygroscopic, chalky solid which is purified by dissolving in water at pH 8.0-8.5, precipitating with phenol, redissolving, and drying. The yield is a brittle, transparent, brown glaze which is nonhygroscopic. Colicine is soluble in water at any p H and in acetic acid, pyridine, and aqueous phenol. It dialyzes through cellophane. It is stable to boiling at pH 2 or 7 for 30 min but is 75% inactivated by boiling at pH 9 for 30 min and 100% inactivated by boiling for 25 min with N / 2 hydrochloric acid or N / 1 0 sodium hydroxide. Colicine is destroyed by pepsin, trypsin, slices of mouse kidney or liver, and the supernatant from centrifuged staphylococcal pus. Small amounts of serum enhance its action. SPECTRUM.—Shigella shigae and Shig. sonnei are approximately as sensitive as the test strain of E. coli. Salmonella enteriditis is 60 times and Salm. paratyphi is 100 times as resistant as the test strain. The following are at least 1,000 times as resistant to colicine as the test strain of Escherichia coli: Escherichia coli, other strains Corynebacterium xerosis El Tor vibrio Mycobacterium phlei Pseudomonas aeruginosa Salmonella newport Salmonella typhi Salmonella typhimurium Shigella flexneri TOXICITY.—Single i.v. injs of 18 mg in 19-20 gm mice produce only transient sickness. Colicine has no effect on human leucocytes at 1:1,000 nor on isolated guinea-pig uterus at 1:5,000. A 1:100 solution of colicine in saline will not lyse human erythrocytes in 20 hr.

Cross references are indicated by

S M A L L CAPITALS

COLICINES

[SS]

EXCRETION.—Colicine is excreted in the urine of mice to the extent of 5% of the amount given. See Heatley and Florey, 1946. colicines, a group of antibiotic substances produced by various strains of Escherichia coli [1], Some colicines resist heating to 100°C.; others are completely or partially destroyed after one-half hr at 70°C. [2], Colicines inhibit some strains of E. coli [1]. Some colicines also inhibit Shigella dysenieriae, Shig. sonnei, and some Salmonellae [1]. Most colicines are inactivated by Bacillus meseruericus, B. subtiHs, and Proteus vulgaris [2]. See [1] Gratia and Fredericq, 1946; [2] Gratia and Fredericq, 1947. coliphages, as test organisms in vitro, see ASPERGILLUS

spp.

colistatin, an antibiotic produced by an aerobic sporulating bacillus. It is extracted from the culture filtrate by acidification, adsorption on charcoal, and precipitation with acetone. Boiling for 15 min does not affect the activity of the culture filtrate. "The unit of colistatin may be defined as that amount of the substance which is just sufficient to inhibit completely the growth of staphylococci (S. aureus) in 1 ml of nutritive broth for 20 hr at 28 °C." Colistatin is bacteriostatic rather than bactericidal. SPECTRUM.—Colistatin inhibits the following in vitro: Escherichia coli Pneumococci Proteus vulgaris Salmonella schottmuelleri Salmonella typhi Shigella dysenteriae Staphylococcus aureus TOXICITY.—Mice tolerate 100,000 units/kg s.c., i.m., or i.v. EXPERIMENTAL CLINICAL RESULTS. — I n t r a m u s c u l a r doses of 30,000 units/kg given every 3 hr for three injs on the day following infection cure mice infected with Borrelia sogdianum. See Gause, 1946a. Colletia armata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Colletotrichum gloeosporioides, a fungus which is affected in vitro by species of Actinomyces as follows: Strongly inhibited by: A. albidoflavus A. alboflavus A. annulatus A. clavijer A. farcinicus A. flavus Kr. A. flavus Mill, et Burr. 'eakly inhibited by: A. albidus A. albus A. aureus A. bobili A. buccalis A. bovis A.cacaoi A. californicus A. caprae A. cellulosae A. chromogenus A. citreus

A. A. A. A. A. A. A.

krainskii madurae microflavtii oligocarbophilus ruber sanninii scabies

A. A. A. A. A. A. A. A. A. A. A.

diastaticus flavogriseus flavovirens gougeroti intermedins langeroni lipmanii macularas odorifer praecox purpeochromogenus

A. craterifer A. dassonvillei A. deri

A. reticuli A. verne A. xanthostroma

Not inhibited by: A. albosporeus A. A. almquisti A. asteroides A. A. baarnensis A. A. canis A. A. carnosus A. A. epidermidis A. A. fimicarius A. A. A. f radii A. A. griseus A. A. halstedii A. A. heimi A. A. keratolytica A. A. lutens A. A. nigrificans A. A. olivaceus A. A. orangicus A. pelletieri See Alexopoulos, 1941.

phaeochromogenus roseodiastaticus roseus rutgersensis salmonicolor sampsonii san f elicei setonii sulphureus tenuis tumuli tyrosinaticus viotaceus-caesari violaceus-ruber viridis viridochromogenus

Colletotrichum lindemothianum, as test organi s m in vitro, s e e ACTINOMYCES ALBUS; BACILLUS SUBTILIS; 2 - M E T H O X Y - 1 , 4 - N A P H T H O Q U I N O N E ; SERRATIA MARCESCENS.

Colletotrichum lini, a fungus which is ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [I], Pseudomonas aeruginosa (U, Salmonella typhi [2], and Endomycopsis albicans [21. The culture media of this fungus are also ineffective against Staph, aureus and Botrytis allii [2], See [1] Wilkins and Harris, 1942; [2] Brian and Hemming, 1947. Colletotrichum nigrum, as test organism in vitro, s e e BACILLUS MESENTERICUS VULGATUS.

Colletotrichum phomoides, as test organism in vitro,

s e e BACILLUS s p .

Collomia coccínea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Ósborn, 1943. Collybia abutyracea, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Collybia acérvala, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [21. See [1] Wilkins, 1947c; [21 Wilkins and Harris, 1944d. Collybia alcalinolens, a fungus, extracts of the sporophores of which are effective in vitro against Staphy lococcus aureus and Escherichia coli. See Mathieson, 1946. Collybia ambusta, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Collybia atratoides, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Collybia cf. atratoides, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Collybia butyracea, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporo-

C r o s s references are indicated

b y SMALL CAPITALS

[89]

COLUTES ARBORESCENS

phores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1) Wilkins, 1947c; [2] Wilkins and Harris, 1944d. Collybia collina, a fungus, the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Collybia conigena, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Collybia distorts, a fungus, extracts of the sporophores of which are ineffective in vitro against Stapylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Collybia dryophila, a fungus which is reported to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Another author reports inhibition of these microorganisms but states that this antibacterial activity may be due to the production of acid [2]. See [1] Wilkins, 1947c; [2] Hervey, 1947. Collybia erythropus, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Collybia extuberans, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Collybia fodiens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Collybia fusipes, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3]. Extracts of the sporophores of this fungus inhibit E. coli but not Staph, aureus and Pseudomonas aeruginosa [4], See [1] Hervey, 1947; [2] Wilkins, 1946b;

coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Collybia prolixa, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Collybia pseudo-clusiiis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Collybia radicata, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3, 4], Extracts of the sporophores of this fungus are also ineffective against Staph, aureus [5, 6], E. coli [5, 6], and Pseudomonas aeruginosa [6]. See [1] Robbins et al„ 1945; [2] Hervey, 1947; [3] Wilkins, 1946b; [4] Wilkins, 1947c; [5] Mathieson, 1946; [6] Wilkins and Harris, 1944d. Collybia rancida, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Collybia tesquorum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Collybia tortipes, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Collybia tuberosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Collybia velutipes, a fungus which is reported

[3] Wilkins, 1947c; [4] Wilkins and Harris, 1944d. Collybia ¡nolens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946. Collybia lancipes, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris. 1944d. Collybia maculata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Sec Wilkins and Harris, 1944d. Collybia maculata v. immaculata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Collybia misera, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Han-is, 1944d. Collybia nitellina, a fungus, extracts of the sporophores of which are ineffective in vitro aganst Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Collybia platyphylla, a fungus, extracts of the sporophores of which are effective in vitro aganst Staphylococcus aureus and Escherichia

a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and b) to inhibit Staph, aureus and/or E. coli [2]. Extracts of the sporophores of this fungus are ineffective against Staph, aureus [3, 4], E. coli [3, 4], and Pseudomonas aeruginosa [4], See [1] Robbins et al., 1945; [2] Wilkins, 1946b; [3] Mathieson, 1946; [4] Wilkins and Harris, 1944d. colon bacilli, as test organisms in vitro, see EUMYCIN.

colon-bacillus bacteremia, clinical, see AUREOMYCIN.

Colpidium spp., as test organisms in vitro, see ACTINOMYCIN.

Colubrina femiginosa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Columnea banksii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Columnea microphylla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Columnea schiediana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Ösborn, 1943. Colutes arborescens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Ösborn, 1943.

Cross r e f e r e n c e s are indicated by SMALL CAPITALS

COMANDRA

RICHARDSIANA

[90]

C o m a n d m richardsiaiia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. C o m a n t h o s p h a c e sublanceoiata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. C o m b r e t u m erythrophyllum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. C o m b r e t u m latifoliuni, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. C o m b r e t u m p u r p u r e u m , a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. C o m i n u m c y m t a u m , a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See C a r d o s o and Santos, 1948. Commelina benghalensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Commelina coelestis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Commelina communis, a higher plant, aqueous extracts of the flowers of which are effective in vitro against Escherichia coli, while aqueous extracts of the leaf are ineffective. Neither of these extracts inhibits Staphylococcus aureus and the spores of Neurospora crassa [1]. Other extracts of this plant are ineffective in the treatment of experimental malaria [2], See [1] Schnell and Thayer, 1949; [2] Spencer et al., 1947. Comptonia peregrina, a higher plant, aqueous and ether extracts of the stem and leaf of which are effective in vitro against Escherichia coli a n d t h e s p o r e s o f Neurospora crassa. Only ether extracts of the stem and leaf inhibit Staphylococcus aureus [1]. Other extracts of this plant are ineffective in the treatment of experimental malaria [2], See [1] Schnell and Thayer, 1949; [2] Spencer et al., 1947. Conandron ramondioldes, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Congea tomentosa v. azurea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coniophora sp., a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Coniophora arida, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa [1], T h e culture media of this f u n g u s are weakly inhibitory for Staph, aureus a n d / o r E. coli [2], See [1] Wilkins and Harris, 1944d; [2] Wilkins, 1947c. Coniophora bourdotti, a fungus, the culture media of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Wilkins, 1947c. Coniophora cerebella, a fungus which is reported a) to be effective in vitro against

Staphylococcus aureus a n d / o r Escherichia coli [1] and b ) to inhibit both these microorganisms [2]. This antibiotic action may be due to the production of acid [2], The culture media of this f u n g u s are weakjy inhibitory f o r Staph, aureus a n d / o r E. coli [3, 4J. See [1] Wilkins, 1946b; [2] Robbins et al., 1945; [3] Wilkins, 1947a; [4] Wilkins, 1947c. Coniophora cystidiophora, a f u n g u s , the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1947c. Coniophora meralioides, a f u n g u s , the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1947c. Coniophora puteana, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Hervey, 1947; [2] Wilkins and Harris, 1944d. As test organism in vitro, see

PINOSYLVINE.

Coniophora suffocata, a f u n g u s which is effective in vitro against Staphylococcus aureus and Escherichia coli [1]. It is also reported t o inhibit Staph, aureus a n d / o r E. coli [2]. See [1] Robbins et al., 1945; [2] Wilkins, 1947b. Coniophora sulfocata, a f u n g u s , the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1947c. Coniophorella olivacea, a f u n g u s , extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. conjunctivitis, clinical, see AUREOMYCIN; BACITRACIN;

PENICILLIN;

STREPTOMYCIN.

Conocarpus erecta, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al, 1947. Conocephalum conicum, a higher plant, aqueous extracts of which cause little or n o inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Conocybe lateritia, a f u n g u s which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Conocybe pubescens, a f u n g u s which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Conopbaryngia ventricosa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Conopodhim denudatum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Convallaria majalis, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1], Bacillus subtilis [2], and Escherichia coli [1. 2], See [1] Osborn, 1943; [2] Sanders et al., 1945. Convolvulus althaeoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Convolvulus arvensis, a higher plant, aqueous extracts of the fruit and leaf of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Otner aqueous ex-

Cross references are indicated by SMALL CAPITALS

[91] tracts of this plant are also ineffective against these two microorganisms [2], In another series of tests in vitro, the root is reported effective against Erwinia caroiovora and Phytomonas tumefaciens; the leaf and stem in vitro inhibit Erwinia carotovora, but neither the leaf and stem nor the root inhibits Staph, aureus and E. coli [3]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943; [3] Hayes, 1947. Convolvulus cordatifolius, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Convolvulus pentapetaloides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Conyza filaginoides, a higher plant, extracts of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Conyza lyrata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cooperia pedunculata, a higher plant, extracts of the bulbs of which are effective in the treatment of experimental malaria. See Spencer et al., 1947. copalchi delgado, common name of a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. copalchi grueso, common name of a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Coprinus sp., a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Coprinus atramentarhis, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores are also ineffective against Staph, aureus [2, 3], E. coli [2, 3], and Pseudomonas aeruginosa [3]. See [1] Wilkins, 1947c; [2] Mathieson, 1946; [3] Wilkins and Harris, 1944d. Coprinus auricomus, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. The culture media of this fungus are weakly inhibitory for Staph, aureus and/or E. coli [2], See [1] Hervey, 1947; [2] Wilkins, 1947c. Coprinus boudierii, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], See [1] Hervey, 1947; [2] Wilkins, 1947c. Coprinus comatus, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1]. The culture media of this fungus are weakly inhibitor) for Staph, aureus and/or E. coli [2], Extracts of the sporophores are reported a) to be ineffective against Staph, aureus and E. coli [3] and b) to be inhibitory for E. coli but not for Staph, aureus and Pseudomonas aeruginosa [4]. See [1] Hervey, 1947; [2] Wilkins, 1947c; [3] Mathieson, 1946; [4] Wilkins and Harris, 1944d. Coprinus coopertus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Coprinus curtus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Coprinus dilectus, a fungus which is ineffective

COPRINUS NYCTHEREMERUS

in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Coprinus domesticus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], See [1] Hervey, 1947; [2] Wilkins, 1947c. Coprinus ephemeras, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1,2], See [1] Hervey, 1947; [2] Wilkins, 1947c. Coprinus erethismus, a fungus, the culture media of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Coprinus extinctorius, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Coprinus fimetarius, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Coprinus fimetarius (?), a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Coprinus fimetarius v. macrorhizus, a fungus, the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1947c. Coprinus friesii, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. The culture media of this fungus inhibit Staph, aureus and E. coli [2], See [1] Hervey, 1947; [2] Wilkins, 1947c. Coprinus hiascens, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Coprinus impatiens, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Coprinus lagopus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Coprinus macrorhizus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Coprinus micaceus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1,2], Extracts of the sporophores are also ineffective against Staph, aureus [3, 4], E. coli [3, 4], and Pseudomonas aeruginosa [4]. See [1] Hervey, 1947; [2] Wilkins, 1947c; [3] Mathieson, 1946; [4] Wilkins and Harris, 1944d. Coprinus miser, a fungus, the culture media of which are effective in vitro against Staphylococcus aureus, but not against Escherichia coli. See Wilkins, 1947c. Coprinus narcoticus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See (1) Wilkins, 1947c; [2] Wilkins and Harris, 1944d. Coprinus niveus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Coprinus nyctheremerns, a f u n g u s which is weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1948.

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

COPRINUS PICACEUS

[92]

Coprinus pkaceus, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. The culture media [2, 3] and mycelial disks [3] of this fungus inhibit both these microorganisms. Extracts of the sporophores are reported to be ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [3]. It is the source from which picacic acid is obtained [4], See [1] Hervey, 1947; [2] Wilkins, 1947c; [3] Wilkins and Harris, 1944d; [4] Pausacker and Philpot, 1947, unpublished. Coprinus plicatilis, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. The culture media of this fungus also inhibit Staph, aureus but not E. coli [2]. Extracts of the sporophores are ineffective against Staph, aureus [3,4], E. coli [3, 4], and Pseudomonas aeruginosa [4]. See [1] Hervey, 1947; [2] Wilkins, 1947c; [3] Mathieson, 1946; [4] Wilkins and Harris, 1944d. Coprinus quadrifidus, a fungus, the culture media of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Coprinus radians, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1,2, 3]. See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1947c. Coprinus radlatus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Coprinus similis, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b) to be ineffective against these microorganisms [2], It is also the source of the antibiotic 5-METHOXYP-TOLUQUINONE.

See

[1]

Hervey,

1947;

[2]

Wilkins, 1947c. Coprinus sphaerophorns, a fungus, the culture media of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Coprinus stercoratius, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], See [1] Hervey. 1947; [2] Wilkins, 1947c. Coprinus sterquilinus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Coprinus urtkaecola, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Coprinus vermiculifer, a fungus, the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1947c. Coprosma baueri, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coprosma baueri v. variegata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coprosma grandifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coptis chinensis, a higher plant of the family Ranunculaceae, from the roots of which an antibacterial substance is derived. The dried crude alcoholic extract is yellow-brown in color and very bitter in taste.

SPECTRUM.—The crude extract is effective in vitro at 1:400 to 1:3,200 against the following: Brucella melitensis Corynebacterium diphtherias Diphtheroids Gamma streptococci Klebsiella pneumoniae Shigella dysenteriae Shigella paradysenteriae Shigella sonnei Staphylococcus aureus Streptococcus hemolyticus Vibrio comma The following microorganisms are inhibited at 1:6,400 to 1:51,200: Bacillus sublilis Brucella abortus Corynebacterium diphtheriae Micrococcus tetragenus Shigella dysenteriae Staphylococcus albus Staphylococcus aureus Staphylococcus citreus The following are unaffected by 1:200: Escherichia coli Proteus OX-19 Pseudomonas aeruginosa Salmonella enteritidis Salmonella paratyphi Salmonella schottmuelleri Salmonella typhi Serratia marcescens TOXICITY.—Two-hundred-gram rats are reported to survive for at least a wk following single i.p. injs of 250 mg/kg [1]. Other authors report that concentrated aqueous extracts of the Chinese drug prepared from the stem and root of C. chinensis are effective in vitro against Staph, aureus but not against E. coli [2], See [1] Chang, 1948; [2] Gaw and Wang, 1949. Corchorus capsularis, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cordia sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cordia alba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cordia monoica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cordyceps capitata, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Wilkins, 1946a. Cordyceps militaris, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Cordyline stricta, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coreopsis drummondli, a higher plant, aqueous extracts of the flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949.

Cross references are indicated by

SMALL CAPITALS

[93] Coreopsis lanceolata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Coriandrum sativum, a higher plant, aqueous extracts of the seed and seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other extracts of this plant are also ineffective against Staph, aureus, E. coli, and Proteus X-19 |2], See [1] Schnell and Thayer, 1949; [2] Cardoso and Santos, 1948. Coriospermum hyssoplfolium, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. corn bacteria. Bacterial spp. isolated from corn plants infected with Ustilago zeae are effective in vitro in inhibiting the growth of Ustilago zeae, U. avenae, U. levis, Sorosporium reilianum, and Tilletia tritici [1], These bacteria consist of a coccus, a motile, nonspore-bearing, rodlike bacterium; a motile, spore-bearing, rodlike bacterium, and a myxobacterium [2]. See [1] Bamberg, 1931; [2] Johnson, 1931. corn, Iowa inbred, a grain plant, extracts of various strains of which are effective in vitro against Staphylococcus aureus, Escherichia coli, Salmonella typhi, Salm. paratyphi, Bacillus stewartii, Erwinia carotovora, Fusarium oxysporum f. niveum, and F. oxysporum f. melonis. See Little and Grubaugh, 1946. corneal ulceration, clinical, sec BACITRACIN; P E N ICILLIN;

STREPTOMYCIN.

Cornus alba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cornus alba v. siblrlca, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Cornus alba v. spaethil, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cornos amomum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cornus canadensis, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. Other extracts are ineffective in the treatment of experimental malaria [2]. See [1] Osborn, 1943; [2] Spencer et al., 1947. Cornus florida, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cornus mas, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Comas nuttallii, a higher plant, some extracts of which are effective [1,2] in vitro and other extracts of which are ineffective [3] against Staphylococcus aureus and Escherichia coli. See [1] Carlson, Douglas, and Robertson, 1948; [2] Carlson and Douglas, 1948a; [3] Osborn, 1943. Comas officinalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Concentrated a q u e o u s extracts of the Chinese drug prepared from the fruit of this plant inhibit Staph, aureus but not E. coli [2],

CORTICIUM COERL'LEUM

See [1] Osborn, 1943; [2] Gaw and Wang, 1949. Cornus sanguinea, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Cornus stolonifera, a higher plant, some extracts of which are effective [1] in vitro and other extracts of which are ineffective [2] against Staphylococcus aureus and Escherichia coli. See [1] Carlson, Douglas, and Robertson, 1948; [2] Osbom, 1943. Cornuta pyramidata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coronilla emerus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coronilla varia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Coronilla viminalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Correa speciosa v. ventricosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Corticium sp., a fungus, extracts of the spirophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Corticium abeuns, a fungus, the liquid culture medium of which is effective in vitro against Staphylococcus aureus in dilutions no greater than 1:64 [1], The fungus inhibits Staph, aureus but not Escherichia coli [2], See [1] Robbins et al., 1945; [2] Wilkins, 1947b. Corticium abeuns (?), a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Robbins et al., 1945. Corticium alutaceum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], See [1] Wilkins, 1947c; [2] Hervey, 1947. Corticium anceps, a fungus, the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1947c. Corticium arachnoideum, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Corticium atrovirens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Corticium bisporum, a fungus, the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Corticium centrifugum, a fungus, the culture media of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Corticium coeruleum, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli

Cross references are indicated by SMALL CAPITALS

CORTICIUM COMEDENS

IM]

[1,2] and b) to inhibit Staph, aureus but not £. coli [3]. See [1] Wilkins, 1947c; [2] Hervey, 1947; [3] Robbins et al., 1945. Cortichim comedens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. C o r t k h u n confine, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Cortkhun conflnens, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. Extracts of the sporophores of this fungus inhibit E. coli but not Staph, aureus and Pseudomonas aeruginosa [2], See [1] Robbins et al., 1945; [2] Wilkins and Harris, 1944d. Cortkhun conigenum, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1]. It is also reported to inhibit Staph, aureus a n d / o r E. coli [2], See [1] Robbins et al., 1945; [2] Wilkins, 1947b. Cortkhun cremorkolor, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Cortkhun eRuscatum, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. The culture media of this fungus also inhibit Staph, aureus but not E. coli [2], See [1] Hervey, 1947; [2] Wilkins, 1947c. Cortkhim fuclforme, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Cortkhim galacttnum, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be ineffective against these two organisms [2]. The culture media are weakly inhibitory for Staph, aureus a n d / o r E. coli [3]. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1947c. Cortkhim hydnans, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3]. See [1] Wilkins, 1948; [2] Robbins et al., 1945; [3] Wilkins, 1947b. Corticium investiens, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Corticium koleroga, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Corticium laeve, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2]. See [1] Wilkins, 1948; [2] Wilkins and Harris, 1944d. Corticium lividum, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b) to be ineffective against these microorganisms [2, 3], See [1] Robbins et al., 1945; [2] Wilkins, 1948; [3] Wilkins, 1947b. Corticium microsclerotia, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Corticium porosum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a.

Cortkhim portentosum, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Cortkhun praetennissom, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortkhim pratkola, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Corticium radio sum, a fungus which is weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1948. Corticium roifsii, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Corticium roseum, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Robbins et al., 1945. Corticium salmonicoior, a fungus which is reported a) to be weakly inhibitory in vitro for Staphylococcus aureus and Escherichia coli [1] and b) to be ineffective against these microorganisms [2]. See [1] Wilkins, 1948; [2] Robbins et al., 1945. Cortichim sambuci, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Corticium solani, as test organism in vitro, see S T R E P T O M Y C E S GRISEUS;

MUSARIN.

Corticium vagum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarhis spp., several unidentified fungi, extracts of the sporophores of some of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the entire plant of others inhibit Staph, aureus [2], See [1] Mathieson, 1946; [2] Atkinson, 1949. Cortinarhis acutus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarhis alboviolaceus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarhis anomalus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarhis arcberi, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Cortinarhis areoiato-hnbricatus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Cortinarhis argentatus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Wilkins, 1946a.

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[95] Cortinarius armeniacus, a fungus, extracts of the sporophores of which are effective in vi/ro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius armiiiatus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius austro-venetus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the fungus itself inhibit Staph, aureus, Salmonella typhi, and Mycobacterium phlei [2]. See [1] Mathieson, 1946; [2] Atkinson, 1949. Cortinarius azureus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius balustinus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Cortinarius basirubescens, a fungus, extracts of which are effective in vitro against Staphylococcus aureus. See Atkinson, 1949. Cortinarius biformis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius bolaris, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius bovinus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius brunneus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius caerulescens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius caesiocyaneus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius calachrous, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius caninus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius castaneo-fulvus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Cortinarius castaneus, a fungus, extracts of the sporophores of which are ineffective in vitro

CORTINARIUS DILUTUS

against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius cáusticos, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Cortinarius cinnabarinus, a fungus, extracts of the sporophores of which are reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Mathieson, 1946; [2] Wilkins and Harris, 1944d. Cortinarius clnnamomeus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius cUduchus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius coiiinitus, a fungus, extracts of the sporophores of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius croceocaeruieus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius croceoconus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Cortinarius crystaliinus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius cyanopus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius damascenus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius deciplens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius decoloratus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius deiibutus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius detonsus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Wilkins, 1946a. Cortinarius diiutus, a fungus, extracts of the sporophores of which are ineffective in vitro

Cross references are indicated by SMALL CAPITALS

CORTINARIUS D U R A C I N U S

[96]

against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius dnracinus, a fungus, extracts of the sporopbores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius elatior, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius elegantior, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarhis emollitus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarhis erythrinus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarhis evernius, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius fasciatus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius flexipes, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius fulgens, a fungus, extracts of the sporophores of which are ineffective in vino against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Sec Wilkins and Harris, 1944d. Cortinarius gentilis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius germanus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius glandicolor, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius glaucopus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius hemitrichus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococccus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius hinnuleus, a fungus, extracts of the sporophores of which are ineffective in vino

against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius holophaeus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarhis iliopodius, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius incisus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius infractus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius intermedius, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius jubarinus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Sec Wilkins and Harris, 1944d. Cortinarius krombholzii, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius largus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [ 1, 2], Escherichia coli [1,2], and Pseudomonas aeruginosa [11. See [1] Wilkins and Harris, 1944d; [2] Mathieson, 1946. Cortinarius lavendulensis, a fungus, extracts of the sporophores of which arc ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Cortinarius lepidopus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius leucopus, a fungus, extracts of the sporophores of v.hich are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius malachius, a fungus, extracts of the sporophores of which arc ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Sec Wilkins and Harris, 1944d. Cortinarius malicorius, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius multiformis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius multiformis v. flavescens, a fungus, extracts of the sporophores of which are cffec-

Cross references aia indicateti by s m a l l c a p i t a l s

[97] tive in vitro :K\iinst S!UPH\/- K'OCCUS aureus but not against f\cherichi.i coli See \\ ilkins, 1946a. Cortinarius (¡blusus. a t'wrig.:-. extracts of the sporophores of which aie ineffective in \itro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Sec Wilkins and Harris, 1944d. Cortinarius ochracco-fulvus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Cortinarius oehroltucus, a lungus, extracts of the sporophores of which arc ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius orichalceus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius paleaceus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius papulosus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius percomis, a fungus which is ineffective in vitro against Staphylococcus aureus and Esherichia coli. See Wilkins, 1948. Cortinarius phoeniceus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius pholideus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius porphyropus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Cortinarius psammocephalus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Cortinarius purpurascens, a fungus, extracts of the sporophores of which are ineffective in \tlro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius reedii, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius renidens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Cortinarius rigidus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius ringeus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli,

CORTINARIUS SUILLIS

and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius rotundisporus, a fungus of the order Basidiomycetes, an aqueous extract of which is effective in vitro against Bacillus subtilis [1], Corynebaclerium diptheriae mitis (1], Escherichia coli [I], Mycobacterium phlei [1], Neisseria catarrhalis [1], Salmonella typhi [1, 2], Staphylococcus aureus [2J, and a group A streptococcus [I], and ineffective against Pseudomonas aeruginosa [1], The extract withstands 100°C. without loss of activity and is also stable to acid and alkali. Its activity is unaffected by serum and thioglycollic acid [1). Colorless, finely divided crystals mixed with a purple amorphous material are obtained when the aqueous extract is extracted with chloroform and evaporated [1]. TOXICITY.—Intramuscular inj of a partially purified extract is without effect in the mouse [1]. See [1] Atkinson, 1946b; [2] Atkinson, 1949. Cortinarius rufo-olivaceus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius saginus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius sanguineus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 21, and Pseudomonas aeruginosa [1]. See [1] Wilkins and Harris, 1944d; 12] Mathieson, 1946. Cortinarius scutulatus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius semisanguineus, a fungus, extracts of the sporophores of which arc ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius sinapicolor, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Cortinarius stemmatus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius subarvinaceus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Cortinarius subcinnamoneus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Cortinarius subferrugineus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Cortinarius soillis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d.

C r o s s r e f e r e n c e s a r e i n d i c a t e d b y SMALL CAPITALS

CORTINARTUS TABULARIS

198]

Cortlnarius tabalarfa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris. 1944d. Cortlnartas torvns, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortlnarius triformis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortlnarius triomphons, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius turbina tus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Cortinarius turgidus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius uliglnosus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cortinarius uracens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Corydalls bulbosa, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Corydalls cheilanthifolla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Corydalls lutea, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Corydalls thalktrifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Osborn, 1943. Corydalls tomentella, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. corylophyline, an a n t i b i o t i c extracted from Pénicillium corylophylum, which is effective in vitro against Escherichia coli communis, staphylococci. Streptococcus hemolyticus, and Trypanosoma equiperdum, and i n e f f e c t i v e against Paramecium caudatum and Spirilla duttoni. It is inactivated by heat and by human or rabbit serum. The course of staphylococcal infections in rabbits is unaffected by administration of this agent. See Levaditi et al., 1944. Corylopsis platypetala, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Corylopsis spicata, a higher plant, aqueous extracts of which are ineffective in vitro against

Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Corylus avellana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Corylus beteropbylla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Corynanthe pachyceras, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Coryne sarcoMes, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Corynebacterium, a microorganism which produces an antibiotic effective in vitro against Actinomyces violaceus and A. aurantiacus, and ineffective against A. griseus and A. globisporus. See Krassilnikov and Koreniako, 1939. Corynebacterium spp., as test organisms in vitro, s e e ANTISMEGMATIS FACTOR; NISIN; STREPTOMYCES AURANTIACUS; S T R E P T O M Y C E S GLOBIG1SPORUS; S T R E P T O M Y C E S GRISEUS; S T R E P T O M Y C E S VIOLACEUS.

Corynebacterium diptberiae. 1 As test organism in vitro, see B A C I L L U S M E S E N T E R I C U S ; B A C I L L U S V U L G A T U S ; BACITRACIN; B I O C E R I N ; C H L O R A M PHENICOL; CHROMOBACTERIUM PRODIGIOSUM; COPTIS CHINENSIS; DICOUMARIN; EUMYCIN; G R A M I C I D I N ; H I R S U T I C ACIDS; I N S E C T I C I N ; K O J I C ACID; LEPTOTAENIA DISSECTA; LEPTOTAENIA MULTIFEDA; LICHENIFORMIN; MYCOPHENOLIC ACID; N E O M Y C I N ; P E N A T I N ; P E N I C I L L I N ; PENICILLIUM EXPANSUM (?); PHTHIOCOL; POLYM Y X I N S ; PROACTINOMYCIN; P S E U D O M O N A S AERUGINOSA; P Y O C O M P O U N D S ; R A N U N C U L U S OCCIDENTALIS; R H U S HIRTA; STREPTOCOCCUS MITIS; SUBTILIN; SULFACTIN; TERRAMYCIN; TYROCIDINE. 2 Experimental infections, see L I C H E N I F O R M I N ; PENICILLIN; STREPTOMYCIN.

Corynebacterium diphtherlae gravis, the causative agent of severe diphtheria, one strain of which is effective in vitro against Bacillus subtilis, Proteus vulgaris. Salmonella paratyphi, and Salm. typhimurium. The strain remains bacteriostatic for 8 mo before losing its activity. See De Lamater and Goodlow, 1947. As test organism in vitro, see A L V E I N ; A Y F I V I N ; B A C I L I P I N A AND B ; F R E Q U E N T I C ACID; F U M I G A C I N ; F U S C I N ; G E O D I N ; L A T E R O S P O R I N A AND B ; L U P U L O N AND H U M U L O N ; M I C R O C O C C I N ; M Y C E TIN; MYCOSUBTILIN; NIDULINE; PENICILLIN; STAPHYLOCOCCUS; STAPHYLOCOCCUS AUREUS; TARD1N.

Corynebacterium diphtherlae intermedius, as test organism in vitro, see A Y F I V I N ; F R E Q U E N T I C ACID; F U S C I N ; G E O D I N ; M I C R O C O C C I N ; M Y C E T I N ; NIDULINE; PERSOONIA PINIFOLIUS; PSALLIOTA XANTHODERMA; STAPHYLOCOCCUS; STAPHYLOCOCCUS AUREUS.

Corynebacterium diphtheriae mitis, as test organism in vitro, see A Y F I V I N ; C O R T I N A R I U S R O TUNDISPORUS; DIPLOICIN; FREQUENTIC ACID; FUSCIN; GEODIN; MICROCOCCIN; MYCETIN; NIDULINE; O N C O P E L T U S FASCIATUS; P E N I C I L L I N ; P E R SOONIA P I N I F O L I U S ; PSALLIOTA XANTHODERMA; STAPHYLOCOCCUS.

Corynebacterium diphtheroides, as test organism in vitro, see C H L O R A M P H E N I C O L . Corynebacterium equi, as test organism in vitro, s e e LICHENIFORMIN: P F . R S O O N I A PSALLIOTA XANTHODERMA.

Cross references are indicated by

SMALL CAPITALS

PINIFOLIUS;

[99] Corynebacterium hoffmannil, as test organism in vitro, see P E R S O O N I A P I N I F O L I U S ; PSALLIOTA XANTHODERMA; PROACTINOMYCIN; PROTOANEMO N I N ; PYO C O M P O U N D S ; STAPHYLOCOCCUS.

Corynebacterium mlchiganense, as test organism in vitro, see ASPERGILLIC ACID; B E R B E R I N E ; C H E I R O L 1 N E ; CLAVACIN; G L I O T O X I N ; M Y C O P H E N O L I C ACID; P E N I C I L L I C ACID; P R O A C T I N O M Y C I N ; SPIRAEA; TYROTHRICIN.

Corynebacterium murium, as test organism in vitro, see P E R S O O N I A P I N I F O L I U S ; P S A L L I O T A XANTHODERMA.

Corynebacterium ovis, as test organism in vitro, s e e LICHENIFORMIN; P E R S O O N I A PSALLIOTA XANTHODERMA.

PINIFOLIUS;

Corynebacterium pseudodiphthericum, as test organism in vitro, see B I O C E R I N . For literature see Rosenfeld and ZoBell, 1947 (marine microorganisms). Corynebacterium pyogenes, as test organism in vitro, see A C T I N O M Y C I N ; C H L O R A M P H E N I C O L ; LICHENIFORMIN.

Corynebacterium renale, as test organism in vitro, see L I C H E N F O R M I N . Corynebacterium sepedonicum, as test organism in vitro, see ASPERGILLIC ACID; B E R B E R I N E ; B U R DOCK; C H E I R O L I N E ; CLAVACIN; G L I O T O X I N ; H E L VOLIC ACID; M Y C O P H E N O L I C ACID; PENICILLIC ACID; P R O A C T I N O M Y C I N ; SPIRAEA; T Y R O T H R I C I N .

Corynebacterium xerosis, as test organism in vitro, see A L V E I N ; A N T I B I O T I C EIr>; A Y F I V I N ; BAC I L I P I N A AND B ; BACILYSIN^ BACITRACIN; C L O S TRIDIUM AEROFEOETIDUM; CLOSTRIDIUM BIFERMENTANS; CLOSTRIDIUM BOTULINUM TYPE A ; CLOSTRIDIUM BUTYRICUM; CLOSTRIDIUM CENTROSPOROGENES; CLOSTRIDIUM CHAUVOEI; C L O S TRIDIUM FALLAX; CLOSTRIDIUM FELSINEUS; CLOSTRIDIUM HISTOLYTICUM; CLOSTRIDIUM MULTIFERMENTANS T E N A L B U M ; CLOSTRIDIUM OEDEMATIENS; CLOSTRIDIUM PARASPOKOGENES; CLOSTRIDIUM PUTRIFICUM; CLOSTRIDIUM SEPT I C U M ; C L O S T R I D I U M SORDELLII; C L O S T R I D I U M SPHENOIDES; CLOSTRIDIUM SPOROGENES; C L O S TRIDIUM TERTIUM; CLOSTRIDIUM TETANI; C L O S TRIDIUM TETANOMORPHUM; CLOSTRIDIUM WELCHII; COLICINE; HERQUEIN; I N U L A SPIRAEIFOLIA; K O J I C ACID; L A T E R O S P O R I N A AND B ; M I C R O C O C C I N ; M Y C O P H E N O L I C ACID; N U D I C ACID A; PHOENICIN; PROTOANEMONIN; PYO COMPOUNDS; RAMEALIN; STAPHYLOCOCCUS; STAPHYLOCOCCUS AUREUS; SUBTILIN C ; SULFACTIN; TARDIN; T H U J A PLICATA. For literature see Gill-

Carey, 1949a (aspergilli).

Coscinium fenestratum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cosmos bipinnatus, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [2]. Aqueous extracts of the seed and entire plant are also ineffective against Staph, aureus and E. coli [3], See [1] Osborn, 1943; [2] Gottshall et al., 1949; [3] Schnell and Thayer, 1949. Costus lucanusianus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cotoneaster dielsiana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cotoneaster divaricata, a higher plant, aqueous extracts of the seeds of which are ineffective in vitro against Staphylococcus aureus, Escher-

CRATAEGUS PYRACANTHA

ichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Cotoneaster frigida, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli See Osborn, 1943. Cotoneaster horizontal is, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Couteria sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Couteria hexandra, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Couteria pterosperma, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Covilla tridentata, a higher plant, also known as Larrea divericata, which produces the antibiotic, NORDIHYDROGUAIARETIC ACID. Cowania stansburiana, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Crambe frutkosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crambe maritima, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crassula arborescens, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al 1949. Crassula circoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crassula lycopodoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crassula partulacea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crassula spathulata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crataegus sp., a higher plant, the fruit of which in vitro inhibits Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Crataegus intricata, a higher plant, aqueous extracts of the seeds of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Crataegus oxyacantha, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crataegus pyracantha, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crataegus pyracantha v. leylandii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Cross references are indicated by

S M A L L CAPITALS

CRATERELLUS CORNUCOPIOIDES

[100]

CratereUos cornncopioidcs, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Willcins and Harris, 1944d. Crepidotns alveolus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Crepidotns applanatus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against these two microorganisms [2]. See [1] Wilkins, 1948; [2] Mathieson, 1946. Crepidotus calolepis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Crepklotus eucalyptorum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Crepidotus fragil is, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Crepidotns cf. globigerus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Crepidotus mollis, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2]. See [1] Hervey, 1947; [2] Wilkins and Harris, 1944d. Crepidotus subhausteliaris, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. crepin, an antibiotic extracted from various parts of the higher plant Crepis taraxacifolia. The active principle occurs as a precursor which is presumably activated by an enzyme occurring principally in the yellow petals and, to a smaller extent, in the roots. A steam extract with no activity acquires full potency after incubation with a raw extract. It is crystallized from ethanol in a variety of crystals which are soluble in pyridine, water, ethanol, ether, and glycerine. The m.p. is above ?00°C. The empirical formula CuHic.Oi is suggested. The activity is destroyed by alkali but is stable to heat and acid. Peptone has no effect on this substance; human serum inhibits its activity. SPECTRUM.—Crepin is effective in vitro a g a i n s t Bacillus subtilis, Salmonella typhi. Staphylococcus aureus, and Streptococcus pyogenes, and is without effect on Pseudomonas aeruginosa. TOXICITY. — Human leucocytes survive 1:4,500,000 solutions of crepin and are killed at 1:4,500. See Heatley, 1944. Crepis biennis, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes. 1947. Crepis capillarls, a higher plant, aqueous extracts of which are effective in vitro against

Staphylococcus aureus but not against Escherichia coli. See Osbora, 1943. Crepis incana, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Crepis taraxacifolia, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. It is also the source of the antibiotic CREPIN. See Osborn, 1943. Crescentia cujete, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crinum sp., a higher plant, extracts of the bulbs of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Crinum americanum, a higher plant, extracts of the bulbs of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Crinum erubescens, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Crinum grandiflorum, a higher plant, extracts of the bulbs of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Crinum longifolium, a higher plant, extracts of the bulbs of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Crinum moorei, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Crithmum maritimum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crocosmia aurea v. imperialis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crocus biflorus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Ösborn, 1943. Crocus sativus, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Proteus X-19 [2], See (1] Osborn, 1943; [21 Cardoso and Santos, 1948. Crocus tommasinianus, a higher plant, aqueous extracts of which arc ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Osborn, 1943. Crocus vermis, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vilro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Crossandra subacaulis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Ösborn, 1943. Crossandra unduiaefolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crossonoma californicum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Cross references are indicated by

S M A L L CAPITALS

[101] Crossoptcryx febrífuga, a higher plunt. extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Crossoptcryx kotschyuna, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Crosso soma bigelovii, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Crotalaria capensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Crotalaria crispata, see cinuNiN. Crotalaria nataiensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Croton sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Croton sp. "copalchi," a higher plant, extracts of the bark of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Croton alamusanus, a higher plant, aqueous extracts of the commercial wood obtained f r o m which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Bacillus antliracis. See Sanchez et al., 1948. Croton californicus, a higher plant, extracts of the branchlets and leaves of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Croton capitatus, a higher plant, extracts of the twigs of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Croton celtidifolius, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See C a r d o s o and Santos, 1948. Croton ciliatoglanduloais, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Croton eluteria, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Croton glabellus, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Croton megalocarpus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Croton aff. niveus, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Croton cf. reflexifolius, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Croton tiglium, a higher plant, extracts of which are ineffective against experimental malaria [1], Concentrated aqueous extracts of the Chinese drug prepared f r o m the seeds of this plant are ineffective in vitro against Staphylococcus aureus and Escherichia coli [2], See [1] Spencer et al., 1947; [2] Gaxv and Wang, 1949. Croton tonduzii, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer, et al., 1947. Crowea saligna, a higher plant, aqueous extracts of which are ineffective in vitro against Staph-

C U C U R B I T A PEPO

ylococcus aureus and Escherichia coli. See Osborn. 1943. Crucianella six losa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Ösborn, 1943. Crucibulum vulgare, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Cryptanthus acaulis, a higher plant, a q u e o u s extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Ósborn, 1943. Cryp'ococcus spp., as test organisms in vitro, see

EUMYCIN.

Cryptococcus hominis. 1 As test organism vitro

see

BACITRACIN;

BORRELIDIN;

TILLANDSIA USNEOIDES. tions,

see

THUJA

2 Experimental

PLICATA;

in

BUTTERCUP;

infec-

BORRELIDIN.

Cryptococcus neoformans, as test organism

in

vitro, s e e ACTIDIONE; ACTINOMYCIN; ANTIBIOTIC 1 3 6 ; ANTIBIOTIC 3 5 1 0 ; ANTIBIOTIC X G ; AUREOMYCIN; BACILLOMYCIN; CHAETOMIN; CHLORAMPHENICOL; FUMIOACIN; LUPULON a n d H U M U L O N ; MYCOSUBTILIN; PENICILLIN; PROTOANEMONIN; S T R E P T O M Y C E S GRISEUS; S T R E P T O M Y C I N ; S T R E P T O T H R I C I N ; S U B T I L I N ; T H U J A P L I C A T A ; in vivo, s e e ACTIDIONE; AUREOMYCIN; PENICILLIN.

Cryptolepis, sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cryptomeria japónica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Ósborn, 1943. Cryptostegia grandiflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ctenomyces asteroides, a fungus which in vitro inhibits the growth of Staphylococcus aureus. See Patiälä, 1947, unpublished. Ctenomyces radians, as test organism in vitro, sec

PHTHIOCOL;

also

CUCUMIS

PLUMBAGOL.

Cucubalus baccifer, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. cucumber, a garden vegetable, extracts of various strains of which are ineffective in vitro against Staphylococcus aureus. Salmonella typhi, Sahn, paratyphi, Fusarium oxysporum f. niveum, F. oxysporum i. melonis, F. oxysporum f. conglutinan*, and F. oxysporum f. lycopersici. Extracts of one strain inhibit Erwinia carotovora. See Little and G r u b a u g h , 1946. See ANGURIA;

CUCUMIS

SATIVUS.

Cucumis anguria, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See C a r d o s o and Santos, 1948. Cucumis sativus, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. Sec C a r d o s o and Santos, 1948. Cucurbita pepo, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1,2], Escherichia coli [1,2], and Proteus X-19 [1]. See [1] C a r d o s o and Santos, 1948; [2] Osborn, 1943. Cucurbita pepo v. ovifera, a higher plant, aqueous extracts of the seed and seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of

Cross references are indicated by SMALL CAPITALS

C U D R A N I A JAVANENSIS

[102]

Neurospora crassa. See Schnell and Thayer, 1949. Cndranla Ja van ends, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cakttiiim rafescow, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Conila origanoldes, a higher plant, extracts of which are ineffective against experimental malaria [1]. In a series of tests in vitro aqueous extracts are reported to show little or no inhibition against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens [2], See [1] Spencer et al., 1947; [2] Hayes, 1947. Cunnlnghamella echinulata, a fungus, the culture media of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1943a. Cnnninghamella elegans, a fungus, the culture media of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1943a. Cnnninghamia sinensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cnphea sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cnpressns benthamii, a higher plant, aqueous extracts of the commercial wood obtained from which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Bacillus anthracis. See Sanchez et al., 1948. Cupressos macrocarpa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Cupressus sempervirens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. curcumin, isolated from the roots of Curcuma tinctoria, completely inhibits the growth of Staphylococcus aureus at a dilution of 1:20,000; Salmonella paratyphi, at 1:20,000; Trichophyton gypseum at 1:10,000; and Mycobacterium tuberculosis at 1:10,000. The empirical formula of curcumin is C2:H2oOo and the structural formula is:

Cuscuta compacts, a higher plant, aqueous but not ether extracts of the flower and stem of which are effective in vitro against Staphylococcus aureus. None of these extracts inhibits Escherichia coli and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Cusp aria angostura, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Cussonia spicata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cyathus striatus, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus a n d / o r Escherichia coli [1], and b) to inhibit Staph, aureus but not E. coli [2], and c) to be ineffective against these two microorganisms [3]. Extracts of the sporophores of this fungus are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [4], See [1] Wilkins, 1946b; [2] Wilkins, 1948; [3] Hervey, 1947; [4] Wilkins and Harris, 1944d. Cydonia japonica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Cydonia japonica v. alba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cydonia oblonca, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cydonia vulgaris, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Cynnara scolymus, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Cynoglossum furcatum, a higher plant, aqueous extracts of the seedling of which are effective in vitro against the spores of Neurospora crassa, while aqueous extracts of the seed and both aqueous and ether extracts of the flower, leaf, stem, and root are ineffective. None of these extracts inhibits Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Cynoglossum virginianum, a higher plant, aqueous extracts of which show little or no inhi-

CH=CH—CO—CH2—CO—CH=CH— < ^ ~ ~ \ O H OCH 3

CHaO See Schraufstetter and Bernt, 1949. "curling factor," see GRISEOFULVIN. Curdsia faglnea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Cnscota sp., a higher plant, extracts of which are effective in vitro a g a i n s t Bacillus subtilis but not against Escherichia coli [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staphylococcus aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [21. See [U Sanders et al., 1945; [21 Hayes, 1947.

bition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Cynophallus caninus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Cynosurus crlstatus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cynoxylon floridus, a higher plant, aqueous and ether extracts of the fruit, leaf, and stem of

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[103] which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Cyperus brasiliensis, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Cyperus odoratus, a higher plant, extracts of wrlich are ineffective against experimental malaria. See Spencer et al., 1947. Cyperus papyrus, a higher plant (papyrus or Egyptian paper plant), aqueous extracts of which are reported to show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Cyrtosperma johnstonii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cystopteris fragilis, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli [1J. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staphylococcus aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2], See [1] Sanders et al., 1945; [2] Hayes, 1947.

DAEDALEA QUERCINA

Cytidia sp., a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Cytidia saiicina, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Cytisus ardoinii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cytisus canadensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cytisus fragrans, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cytisus kewensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cytisus purpureum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Cytisus ratisbonensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

D Daboecia polifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. dacryocystitis, clinical, see P E N I C I L L I N . Dacryomyces deliquescens, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this f u n g u s are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Wilkins, 1948; [2] Wilkins and Harris, 1944d. Dactylina arctica, a lichen, extracts of which are effective in vitro against Staphylococcus aureus a n d / o r Bacillus subtilis. See Burkholder and Evans, 1945. Dactylis glomerata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumejaciens [2], See [1] Osborn, 1943; [2] Hayes, 1947. Dactylium dendroides, a fungus effective in vitro against Hymenomycetes. See Bisby et al., 1933. Daedalacanthus nervosus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Daedalea ambigua, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1,2, 3]. See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1948. Daedalea biennis, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1,2, 3]. Extracts of the sporo-

phores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [4]. See [1] Hervey, 1947; [21 Wilkins, 1947a; [3] Wilkins, 1948; [4] Wilkins and Harris, 1944d. Daedalea confragosa, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [ 1 , 2 ] and b ) to inhibit Staph, aureus but not E. coli [3]. See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1948. Daedalea flavida, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b ) to be ineffective against these two microorganisms [2,3]. See [1] Hervey, 1947; [2] Wilkins, 1946b; [3] Wilkins, 1948. Daedalea gibbosa, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1,2]. See [1] Hervey, 1947; [2] Wilkins, 1948. Daedalea heteromorpha, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. This antibiotic action may be due to the production of acid [1]. It is also reported to inhibit Staph, aureus but not E. coli [2]. See [1] Robbins et al., 1945; [2] Wilkins, 1947b. Daedalea juniperina, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], This antibiotic action may be due to the production of acid [1], It is also reported to inhibit Staph, aureus a n d / o r E. coli [3]. See [1] Robbins et al., 1945; [2] Wilkins, 1948; [3] Wilkins, 1947b. Daedalea quercina, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus a n d / o r Escherichia coli [1] and b ) to inhibit both these microorganisms [2, 3],

Cross references are indicated by SMALL CAPITALS

DAEDALEA UNICOLOR

[1041

This antibiotic action may be due to the production of acid (2, 3]. Extracts of the sporophores of this fungus are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [4]. See [1] Wilkins, 1946b; [2] Robbins et al., 1945; [3] Hervey, 1947; [4] Wilkins and Harris, 1944d. Daedalea untcolor, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1, 2] and b) to be ineffective against these two microorganisms [3]. The culture media of this fungus are reported a) to be strongly inhibitory for Staph, aureus and/or E. coli [4] and b) to inhibit Staph, aureus at 1:256 [2]. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1948; [4] Wilkins, 1947a. Dahlia, a higher plant, aqueous extracts from garden hybrids of both the large single and the pompom variety of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dahlia merckii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dahlia pinnata, a higher plant, aqueous extracts of the tuber and leaf of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Dahlia variabilis, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Mycobacterium tuberculosis but not against Escherichia coli. See Gottshall et al., 1949. Dais cotonifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dalbergia cf. laevigata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Dalbergia nigra, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Daldjnia concentrlca, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores of this fungus are also ineffective against these two microorganisms [2]. See [1] Wilkins, 1946b; [2] Wilkins, 1946a. Dalechampia roezliana, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Dalhousianus pentstemonoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Daphne blagayana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Daphne burkwoodil, a higher plant, aqueous extracts of the garden hybrid of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Daphne cannabina, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Daphne cneorum, a higher plant, aqueous extracts of which are ineffective in vitro against

Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Daphne laureoia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Daphne mezereum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Daphne tangutka, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Daphniphyllum macropodhun, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Darwinia sp., a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi. See Atkinson, 1949. Darwinia citriodora, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi. [1, 2], See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Darwinia collina, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonalla typhi. See Atkinson, 1949. Dascyscypha luteola, a fungus, extracts of the sporophores of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus. See Wilkins, 1946a. Dasychyra pudlbunda, an insect, the blood of which contains an antibiotic, INSECTICIN. Datisca cannabina, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. See also DATISCETIN.

Datisca glomerata, a higher plant, extracts of the roots of which are effective in the treatment of experimental malaria. See Spencer et al., 1947. datiscetin, an antibiotic which is derived from Datisca cannabina and which is effective against Staphylococcus aureus and Bacillus anthracis. It crystallizes in yellow needles, its m.p. is 270° C., and it is soluble in dilute alkali, in alcohol, and in ether; it is only slightly soluble in water. The empirical formula is CisHioOo • H2O. The structural formula is given as follows: OH O. HO

rO

HO So See Osborn et al., 1948, unpublished. Datura inermis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Datnra sanguinea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Datura stramonium, a higher plant, some extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli

Cross references are ildicated by SMALL CAPITALS

[105] [1] and others of which are ineffective against Staph, aureus [2], E. coli [2, 3], and Bacillus subtilis [3], Aqueous and ether extracts of the leaf, stem, and root of this plant are ineffective against Staph, aureus, E. coli, and the spores of Neurospora crassa [4]. See [1] Carlson, Douglas, and Robertson, 1948; [2] Osborn, 1943; [3] Sanders et al., 1945; [4] Schnell and Thayer, 1949. Datora suavoiens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Datura tatula, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Daucus carota, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2, 3], Escherichia coli [1, 2, 3, 4], Mycobacterium tuberculosis [2], Bacillus subtilis [4], and Proteus X - 1 9 [3]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [5], See [1] Osborn, 1943; [2] Gottshall et al., 1949; [3] Cardoso and Santos, 1948; [4] Sanders et al., 1945; [5] Hayes, 1947. Daucus carota v. sativa, a higher plant, aqueous extracts of the seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Davidia involucrata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Debaryomyces ayrocola, as test organism in vitro,

see

TORULA

SUGANII.

Debaryomyces globosum, as test organism in vitro, see ACTIDIONE. Debaryomyces gruetzii, as test organism in vitro, see

MYCOSUBT1LIN.

Debaryomyces

membranaefaciens,

as test

or-

g a n i s m in vitro, s e e ASPERGILLUS FACTOR; L U P U L O N AND H U M U L O N ; RHIZOCTONIA FACTOR.

Debaryomyces mucosus, see YEASTS. Debaryomyces nadiformis, as test organism in vitro, see PUROTHIONIN. Debregeasia longifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Decodon verticillatus, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. . Deconica crobula, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Deconica inquilina, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Deherainia smagdarina, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Delphinium ajacis, a higher plant, aqueous extracts of the seed, seedling, flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli,

DERRIS

ELLIPTICA

and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Delphinium cheiianthum, a higher plant, aqueous extracts of the leaf and stem of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Other aqueous extracts of this plant are also ineffective against these two microorganisms [2], See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Delphinium gayanum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Delphinium grandiAorum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Delphinium tatsienense, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dematium sp., a fungus, extracts of which are effective in vitro against Trypanosoma equiperduin. See Schatz et al., 1946. Dematium spp., as test organisms in vitro, see

A C T I N O M Y C I N ; C H A E T O M I N ; CLAVACIN; F U M I G A CIN; GLIOTOXIN; S T R E P T O M Y C I N ; STREPTOTHRICIN.

Dematium pullulans, as test organism in

vitro,

Dematophora necatrix, as test organism in

vitro,

see

PEZIZA

SCLEROTIORUM.

see

BACILLUS

VULGATUS.

Dendrium boxifolium, a higher plant, aqueous extracts of the fruit and leaf of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Dendrium canadense, a higher plant, aqueous and ether extracts of the stem and leaf of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Dendropanax Japonicum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Dentaria laciniata, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Deringa canadensis, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Dcrmacentroxenus rickettsi, experimental infections, see CHLORAMPHENICOL. Dermatobotrys saundersiae, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dermatocarpon min latum, a lichen, extracts of which are effective in vitro against Staphylococcus aureus and/or Bacillus subtilis [1J. Extracts of this lichen are also reported to inhibit Staph, aureus but not Escherichia coli [2]. See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Derris elliptka, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Cross references are indicated by SMALL CAPITALS

DERRIS MALACCENSIS

[106]

D c r r b maiaccensls, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. D c a n o d k u n gyrans, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. destruin, an antibiotic isolated from Irpex destruens and weakly effective in vitro against Staphylococcus aureus, Streptococcus pyogenes, and Bacillus anthracis. It is a yellow oil containing only carbon, hydrogen, and oxygen. It is slightly soluble in water and very soluble in ether, benzene, acetone, and ethanol. It is stable at pH2-pH7 at rm. temp. At pH9 it is slowly inactivated. See Pausacker, 1947, unpublished. Deuterophoma tracheiphila, as test organism in vitro,

see FUSARIUM sp.

Deutzia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Deutzia gracilis, a higher plant, aqueous extracts o f which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Deutzia sessilifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Deutzia setcbenensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dianthera americana, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli [1], In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staphylococcus aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2], See [1] Sanders et al., 1945; [2] Hayes, 1947. Dianthera nodosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Dianthos armeria, a higher plant, aqueous extracts of the flower, leaf, and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Dianthus barbarus, a higher plant, aqueous extracts of the leaf and stem of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Dianthos barbatus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dianthns caryophyllns, a higher plant, ether extracts of the leaf and stem of which are effective in vitro against Escherichia coli, while ether extracts of the flower and aqueous extracts of the seed, seedling, leaf, stem, and flower are ineffective. None of the extracts mentioned inhibits Staphylococcus aureus and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Dianthus fragrans, a higher plant, aqueous extracts of which are ineffective in vitro against

Staphylococcus aureus and Escherichia coll. See Osborn, 1943. Dianthus, hybrid, a higher plant, aqueous extracts of the root and aqueous and ether extracts of the flower and leaf of which are effective in vitro against the spores of Neurospora crassa, while aqueous and ether extracts of the stem are ineffective. None of these extracts inhibits Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Dianthus phimarius, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. diarrhea, epidemic, of newborn, clinkal, see PENICILLIN;

STREPTOMYCIN.

Dicentra canadensis, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Dicentra exima, a higher plant, aqueous extracts of the flower, leaf, and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Dicentra spectabills, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dichapetalum cymosa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Dichorisandra thyrsiflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dichotomanthes tristaniaecarpa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dichroa febrifuga, a higher plant (known in China as "Ch'ang Shan"), crystalline derivatives of various parts of which are effective in the treatment of malaria [1, 2]. Two active crystalline alkaloids, designated as alkaloids I and II, are obtained from the roots by boiling the latter with methanol, evaporating, adjusting to pH 8, and extracting with chloroform and hydrochloric acid. The two compounds are then separated by chromatography. Alkaloid I melts at 131°-132°C. and has the probable formula C1GH10N3O3; alkaloid II melts at 140°-142°C. and has the same probable empirical formula as alkaloid I. Both are optically active. In the treatment of malarial chicks, 5 mg/kg of alkaloid I or 2.5 mg/kg of alkaloid II is equivalent to 40 mg/kg of quinine, while 10 mg and 5 mg/kg, respectively, are toxic [2]. Another extract of the root of this plant is reported to be equal to quinine in controlling fever in human tertian malaria but somewhat slower in its antiparasitic effect. In clinical trials, nausea and vomiting are the only symptoms of toxicity. Extracts of the roots and leaves are effective in controlling Plasmodium gaUinaceum infections in chicks but do not prevent relapses [1]. The LD-.o in dogs is 20 gm 'kg; in ducklings, 22 gm/kg; and in chicks, 14 gm/kg [1], Of four crystalline substances which have been isolated from these extracts, only one,

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

DIOSPYROS MOLLIS

[107] designated as dichroine B, is effective against chicken malaria. It is an alkaloid with a m.p. of 237°-238°C. (decomp.) [1], Concentrated aqueous extracts of the Chinese drug prepared from D. febrífuga are effective in vitro against Staphylococcus aureus but not against Escherichia coli [3], Aqueous extracts of the plant itself are reported to be ineffective against these two microorganisms [4]. Extracts of the roots, stems, and leaves are effective in the treatment of experimental malaria [5], See [1] Jang et al., 1946; [2] Kuehl, Spencer, and Folkers, 1948; [3] Gaw and Wang, 1949; [4] Osborn, 1943; [5] Spencer et al., 1947. dichroine B, an antimalarial extract from the higher plant D I C H R O A F E B R Í F U G A . Dicksonia antarctica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. dicoumarin, a white, crystalline compound, 3,3' m e t h y l e n e bis (4-hydroxycoumarin), which occurs in spoiled sweet clover. It has the following antibacterial properties: Organism Inhibitory concentration Bacillus anthracis 1:100,000 Bacillus subtllis not inhibited at 1:25,000 Brucella abortus 1:25,000 Clostridium welchii not inhibited at 1:25,000 Corynebacterium diphtheriae 1:25,000 Escherichia coli not inhibited at 1:25,000 Proteus vulgaris not inhibited at 1:25,000 Pseudomonas aeruginosa not inhibited at 1:25,000 Salmonella paratyphi not inhibited at 1:25,000 Salmonella typhi not inhibited at 1:25,000 Staphylococcus aureus 1:100,000 Streptococcus fecalis not inhibited at 1:25,000 Streptococcus pyogenes 1:100,000 Streptococcus viridans 1:100,000 See Goth, 1945b. dicoumarol. See D I C O U M A R I N . Dictamnus albus, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and in vivo against experimental malaria [2], See [1] Osborn, 1943; [2] Spencer et al., 1947. Dicyrta warscewieziana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Didlscus caeruleus, a higher plant, aqueous extracts of the seed, seedling, flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Digitalis dubia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Digitalis lutea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Digitalis purpurea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Digitalis purpurea v. gloxtniaflora, a higher plant, aqueous extracts of seed and seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Digharia sanguinalis, a higher plant, various extracts of which are ineffective in vitro against Bacillus subtilis [1], Escherichia coli [1, 2], Staphylococcus aureus [2], and Mycobacterium tuberculosis [2], See [1] Sanders et al., 1945; [2] Gottshall et al., 1949. dihydrofuscin, see F U S C I N . Dimorphotheca aurantica, a higher plant, aqueous extracts of the flower and root but not of the seed, seedling, leaf, and stem of which are effective in vitro against Staphylococcus aureus. None of these extracts inhibits Escherichia coli and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Dimorphotheca barberiae, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dioclea coriaceae, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dioscorea adenocarpa, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli and Proteus X-19. See Cardoso and Santos, 1948. Dioscorea balcanica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dioscorea batatas, a higher plant, aqueous extracts of the bulblet and aqueous and ether extracts of leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Dioscorea dodecaneura, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Dioscorea glauca, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Dioscorea heptaneura, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Dioscorea macroura, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dioscorea sativa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dioscorea villosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Diospyros abenum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Diospyros mollis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Cross references are indicated by

SMALL CAPITALS

DIOSPYROS POEPPIGIANA

11081

Dlospyros poeppigbuu, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Dlospyros rirgjniaiia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, tumeErwinia carotovora, and Phytomonas faciens [2]. See [1] Osborn, 1943; [2] Hayes, 1947. Dtpelta floribnnda, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. diphtheria, carrier state, clinical, see PENICILLIN. diphtheroids, as test organisms in vitro, see BACITRACIN; C o P T I S ROCIDINE.

CHINENSIS;

GRAMICIDIN;

TY-

Diphysa robin k) ides, a higher plant, extracts of the branchlets and leaves of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. diplococcin, an antibiotic substance occurring in the cells of a strain of streptococci isolated from cheese starter. The active material is obtained by drying and powdering the cells and repeated refluxing with water and acetic acid. After its conversion to the picrate by shaking with Esbach's reagent, the salt is suspended in ethanol, and acetic acid is added. The creamcolored residue which remains after centrifuging is crude diplococcin. The active principle is thermostable in acid solution but its activity is destroyed by heat in alkaline solution. SPECTRUM. — A. 1:2 million dilution is effective in vitro against Streptococcus cremoris. Diplococcin is somewhat less effective against Staphylococcus aureus and Strep. Iactis, and is ineffective against Escherichia coli. See Oxford, 1944. Dtplococcos pneumoniae. 1 As test organism in vitro, s e e ACTINOMYCIN; ANTIBIOTIC X G ; ASPERGILLIC ACID; AUREOMYCIN; BACILLIN; CHLORAMPHENICOL; EPIDERMOPHYTON FLOCCOSUM; GRAMICIDIN; GRAMICIDIN S ; K O J I C ACID; L E P T O TAENIA D I S S E C T A ; LEPTOTAENIA MULTIFEDA; L I C H E N I F O R M I N ; LUPULON AND H U M U L O N ; M I CROSPORUM AUDOUINI; NIDULINE; PENATIN; P E N ICILLIN; PHTHIOCOL; POLYMYXINS; P O L Y P E P T I N ; PROTOANEMONIN; PYO COMPOUNDS; R A N U N C U LUS OCCIDENTALIS; R H U S HIRTA; STREPTOMYCIN; STREPTOTHRICIN; SUBTENOLIN; SUBTILIN; SULFACTIN; TERRAMYCIN; TRICHOPHYTON MENTAGROPHYTES; TRICHOPHYTON RUBRUM; T R I C H O PHYTON TONSURANS; TRICHOPHYTON VIOLACEUM;

TYROCIDINE; TYROTHRICINE. F o r

literature

OCH»

see

Burkholder and Evans, 1945 (lichens). 2 For results in experimental infections, see AUREOMYC I N ; BACILLIN; CHLORAMPHENICOL; PYO C O M POUNDS; R A N U N C U L U S OCCIDENTALIS; STREPTOTHRICIN; SUBTILIN; SULFACTIN; TERRAMYCIN. F o r

literature see Carlson et al., 1946 (higher plants). dipiokin, a water-insoluble compound (I) isolated from the lichen Buellia canescens. Neutral solutions of its soluble derivative (II) i n h i b i t Corynehacterium diphtheriae mitis, Mycobacterium smegma, and Mvco. tuberculosis in dilutions of 1:70,000-1:100,000. See Barry, 1946.

Diploiaena grandiflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Diplotaxis muralis, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Dipodascus uninucleates, as test organism in vitro,

see MYCOSUBTILIN.

vitro,

s e e LUPULON AND H U M U L O N .

Dipsacus sylvestris, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [2], In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [3]. See [1] Osborn, 1943; [2] Gottshall et al., 1949; [3] Hayes, 1947. Discomyces mexicanus, as test organism in Dlsporum lanuglnosum, a higher plant, aqueous extracts of the berry and stem but not of the leaf of which are effective in vitro against the spores of Neurospora crassa. Only aqueous extracts of the berry inhibit Staphylococcus aureus. None of these extracts inhibits Escherichia coli. See Schnell and Thayer, 1949. Dissotis plumosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. distemper, experimental, see AUREOMYCIN; CHLORAMPHENICOL.

Distylhim raeemosum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ditremexa leptocarpa, a higher plant, extracts of the branchlets and leaves of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Dodecatheon media, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2], See [1] Osborn, 1943; [21 Hayes, 1947. Dodonaea ehrenbergii, a higher plant, aqueous extracts of which are ineffective in vitro against

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[109] Staphylococcus aureus and Escherichia coli. See Osborn, 1943. dog cecum, amhracidal activity, see MAMMALIAN TISSUES,

EXTRACTS,

dog leucocytes, anthracidal activity, see MAMMALIAN TISSUES, EXTRACTS.

Dolichan drone hlidebrandii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dolichos lablab, a higher plant, aqueous extracts of the flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Dondonaea viscosa v. angustifolia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Doronicum pardaliancbes, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dorotheanthus criniflorus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dorstenia arifoiia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dorstenia barteri, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dorstenia contrajerva, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dorstenia elata, a higher plant, aqueous extracts of which in vitro inhibit Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dorstenia mannii, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dorstenia massonii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dorstenia torneraefolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dothiorella gregarls, as test organism in vitro, s e e PSEUDOMONAS

JUGLANDIS.

Draba aizoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dracaena sp., a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dracaena godselfiana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dracaena surculosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dracephyllum ruyschiana, a higher plant, aqueour extracts of which are ineffective in vitro

DROSOPHILA LACTEA

against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dracocephalum moidavicum, see PHYTONCIDES. Drimys colorsta, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Drimys winter!, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and in vivo against experimental malaria [2]. See [1] Osborn, 1943; [2] Spencer et al., 1947. Drosera juniperina, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Salmonella typhi. See Atkinson, 1949. Drosera peltata, a higher plant which produces an antibiotic substance active in vitro against Staphylococcus aureus and Salmonella typhi. The active principle is obtained by reducing the dried plants to a powder, extracting with alcohol, and evaporating. Heating the residue yields an active, o r a n g e - y e l l o w sublimate. Steam distillation of the alcohol residue, followed by ether extraction and chromatography, yields active yellow crystals. See Atkinson, 1949. Drosera rotandifolia, a higher plant, aqueous and ether extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. [1]. Other aqueous extracts of this plant are also ineffective against Staph, aureus and E. coli [2], See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Drosera whittakeri, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Salmonella typhi. See Atkinson, 1949. Drosophila sp., a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Drosophila appendkulata, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Drosophila badia, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Drosophila candolleana, a f u n g u s which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Drosophila caudata, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Drosophila exalbleans, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Drosophila fatua, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Drosophila fibrillosa, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Drosophila gracilis, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Drosophila bydrophila, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Drosophila lactea, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947.

C r o s s references are indicated by SMALL CAPITALS

DROSOPHILA MARCESCIB1LIS

[110]

Drosophila marcescflrilis, a fungus which is effective in vitro against Staphylococcus aureus but not Escherichia coli. See Hervey, 1947. Drosophila orbKarum, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Drosophila prooa, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Drosophila pygmaea, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Drosophila sarocephala, a fungus which is effective in vitro against Staphylococcus aureus but not Escherichia coli. See Hervey, 1947. Drosophila semlvestita, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. The culture media inhibit Staph, aureus at 1:64. See Hervey, 1947. Drosophila spadkophylla, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Drosophila subatrata, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. The culture media inhibit Staph, aureus at 1:64-1:2,048. See Hervey, 1947.

Drosophila treplda, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Drosophila vemalis, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Dryas octopetala, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Drymonla sp., an insect, the blood of which contains an antibiotic, INSECTICIN. Dryopteris felix-mas, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. duomycin, see AUREOMYCIN. Durante lorentzii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Duranta plumleri, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. dysentery, baclllary, clinical, see PENICILLIN; STREPTOMYCIN.

E Eberthella paradysenteriae. 1 See SHIGELLA PARA D Y S E N T E R Y . 2 As test organism in vitro, see PSEUDOMONAS

FLUORESCENS. 1 See BACILLUS T Y P H O S U S ; BACTERIUM TYPHOSUM; SALMONELLA TYPHI. 2 As test organism in vitro, see P S E U D O M O N A S FLUORESCENS; P U R O T H I O N I N .

Eberthella typhi

EcbalUum elaterium, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and in vivo against experimental malaria [2], See [1] Osborn, 1943; [2] Spencer et al., 1947. Eccilia cameogrisea, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Echinodontfum tinctorhim, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1,2]. It is also reported to inhibit Staph, aureus and/or E. coli [3], See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1947b. Echinops sphaerocephalus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Echites rubrovenosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. egg albumen, see LYSOZYME. Ehretia tinifolla, a higher plant, extracts of the bark of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Eichhornia crassfpes, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Eicbleriella spinulosa, a fungus, extracts of the sporophores of which are ineffective in vitro

against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Eldamia catenulata, a fungus which is ineffective in vitro against Staphylococcus aureus, Salmonella typhi, and Endomycopsis albicans. The culture media of this fungus are ineffective against Staph, aureus and Botrytis allii. See Brian and Hemming, 1947. Elaeagnus multiflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Elaeagnus pungens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Elaphomyces variegatus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Elaphrium grandifolium, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Elaphrium mtcrophyllum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Elaphrium simarnba, a higher plant, aqueous extracts of the commercial wood obtained from which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Bacillus anthracis [1], Aqueous extracts of the fruit are slightly effective in the treatment of experimental malaria [2], See [1] Sanchez et al., 1948; [2] Spencer et al., 1947. Eleocharis tuberosa, a higher plant (the Chinese water chestnut), the source of PUCHIIN. Elephantopus nudatus, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Eleusine indica, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli [1]. In another

Cross references are indicated by

SMALL CAPITALS

[Ill] series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staphylococcus aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [21. See [1] Sanders et al., 1945; [2] Hayes, 1947. Elodea canadensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Elodea densa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Emilia sonchifoiia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. empyema. 1 Clinical, see G R A M I C I D I N S, P E N I C I L LIN,

STREPTOMYCIN;

TYROTHRICIN.

2

Of

the

gall bladder, clinical, see PENICILLIN; STREPTOMYCIN.

Encapsulates pneumoniae, as test organism in vitro,

see

PSEUDOMONAS

FLUORESCENS. encephalomyelitis, experimental, see A U R E O M Y C I N ; BACILLUS SUBTILIS.

Endameba histolytica. 1 As test organism in vis e e AUREOMYCIN; CHLORAMPHENICOL; PROtro, ACTINOMYCIN; STREPTOMYCIN; UMBELLATINE.

2 Experimental infections in vitro, see CHLORAMPHENICOL;

endocarditis.

GRAMICIDIN;

1 Acute

STREPTOMYCIN.

Gram-negative

2

SIMAROUBIDIN.

bacterial,

Clinical,

bacillary

see

clinical,

c l i n i c a l , s e e AUREOMYCIN; PENICILLIN.

acute

bacterial,

clinical,

see

CHLORAMPHENICOL; PENICILLIN; TERRAMYCIN.

see

BACITRACIN.

subacute

3

bacterial, 4

Sub-

AUREOMYCIN;

STREPTOMYCIN;

Endoconidiophora adiposa, a fungus which gives doubtful results when tested in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Endoconidiophora coernlescens, a fungus which gives doubtful results when tested in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Endodermophyton indicum, as test organism in vitro, s e e ASPERGILLIC ACID; C H E I R O L I N E ; CLAVACIN; FUMIGACIN; GLIOTOXIN; MYCOPHENOLIC ACID; P E N I C I L L I C ACID; P E N I C I L L I N ; P R O A C T I N O MYCIN.

Endodermophyton tropicale, as test organism in

vitro, s e e ASPERGILLIC ACID; C H E I R O L I N E ; CLAVACIN; FUMIGACIN; GLIOTOXIN; MYCOPHENOLIC ACID; P E N I C I L L I C ACID; P E N I C I L L I N ; PROACTINOMYCIN.

Endomyces albicans, a mold, the culturc media of which are ineffective in vitro against Mycobacterium tuberculosis. See Zorzoli, 1940 a and b. Endomyces magnusii, as test organism in vitro, see

ACTIDIONE.

Endomycopsis albicans, as test organism in vitro, s e e ASPERGILLIC ACID; C H E I R O L I N E ; F U M I G A C I N ; G L I O T O X I N ; P E N I C I L L I C ACID; P E N I C I L L I N , PROACTINOMYCIN; P U R O T H I O N I N ; TARDIN. For

literature see Brian a n d H e m m i n g , 1947 (fungi). endophthalmitis, clinical, see A U R E O M Y C I N ; P E N ICILLIN;

STREPTOMYCIN.

endosobtilysin, an antibiotic extracted f r o m Bacillus subtilis and active in vitro against Staphylococcus aureus. Intravenous injs of 3 cc are not lethal to rabbits. Human beings tolerate i.V., i.m., and intraspinal injs. See de Saint-Rat and Olivier, 1946.

ENTOLOMA PRUNULOIDES

enniatin, a colorless crystalline antibiotic extracted from the mycelium of Fusarium ortho* ceras v. enniatinum. The mol. wt. is 443 ± 1 3 ; m.p., 121°-122 C C.; probable formula, C24H24 OiiN.i. Enniatin is insoluble in water. It is inactivated rapidly by alkali and more slowly by acid. It is effective in vitro against Bacillus subtilis, Mycobacterium paratuberculosis. Myco. phlei, Myco, tuberculosis hominis, and Staphylococcus aureus, and ineffective against Escherichia coli. See Gäumann, Roth, Ettlinger, Plattner, and Nager, 1947. Entelea arborescens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. enterococci, as test organisms in vitro, see PSEUDOMONAS.

Enterococcus, as test organism in vitro,

see

NIDULINE.

Enterococcus sp., as test organism in vitro, see NOTALYSIN.

Enteroloblum cyclocarpum, a higher plant, aqueous extracts of the commercial wood obtained f r o m which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Bacillus anthracis. See Sanchez et al., 1948. Entoloma ameides, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Entoloma bloxhamii, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Entoloma clypeatum, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Entoloma griseocyaneum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Entoloma jubatum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Entoloma lividum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Entoloma niderosum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Entoloma niderosum v. umbilicatum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Entoloma porphyrophaeum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Entoloma prunuloides, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli,

Cross references are indicated by SMALL CAPITALS

ENTOLOMA RHODOPOUUM

[Ili]

and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Entotoma rbodopoUom, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Entotoma wriceom, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2]. See [1] Wilkins, 1947c; [2] Wilkins and Harris, 1944d. Epacris impressa v. longHlora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ephedra dlstachya, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ephedra sinka, a higher plant, concentrated aqueous extracts of the Chinese drug prepared from the stem of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Gaw and Wang, 1949. Eptcoccum nigrum, as test organism in vitro, s e e L U P U L O N AND H U M U L O N .

Eplcoccum oryzae, a fungus which is ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1942. Epidermophyton spp., as test organisms in vitro, see

GLIOTOX1N.

Epidermophyton cruris, as test organism in vitro, s e e ASPERGILLIC ACID; CHEIROLINE; CLAVAC I N ; FUMIGACIN; GLIOTOXIN; MYCOPHENOLIC ACID; PENICILLIC ACID; P E N I C I L L I N ; PROACTINOMYCIN.

Epidermophyton floccosum, a fungus which in vitro inhibits the growth of Staphylococcus aureus [1]. It is further reported to elaborate a factor in vitro which is antagonistic to Staph, aureus, Streptococcus hemolyticus, Diplococcus pneumoniae, Neisseria catarrhalis, and Clostridium perfringens. This fungus is inactive against penicillin-resistant Staph, aureus, Strep, fecalis, Bacillus subtilis, Aerobacter aerogenes, Serratia marcescens, Alcaligenes fecalis, Salmonella enteritidis, and Escherichia coli [2]. See [1] Pätiälä, 1947; [2] Peck and Hewitt, 1945. For results as test organism in vitro. s e e ANTIBIOTIC 1 3 6 ; ANTIBIOTIC X G ; ASPERGILLUS FLAVUS; BACILLOMYCIN; CHLORAMPHENICOL; EUMYCIN; LYCOPERSICUM PIMPINELLIFOLIUM; MYCOPHENOLIC ACID; P O L Y P E P T I N ; SOLANINE; T H U J A PLICATA.

Epidermophyton inguinale, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Robbins et al., 1945. As test organism in vitro, see MYCOSUBTILIN.

Epidermophyton perneti, as test organism

in

vitro, s e e ASPERGILLIC ACID; CHEIROLINE; CLAVACIN; FUMIGACIN; GLIOTOXIN; MYCOPHENOLIC ACID; PENICILLIC ACID; P E N I C I L L I N ; PROACTINOMYCIN.

Epidermophyton rubrum, as test organism in vitro, s e e ASPERGILLIC ACID; CHEIROLINE; CI.AVAC I N ; FUMIGACIN; GLIOTOXIN; PENICILLIC ACID; PENICILLIN; PROACTINOMYCIN.

epididymitis, gonorrheal, clinical, see PENICILLIN.

Epilobhim angustifolhim, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Epilobhim dodonaei, a higher plant, aqeuous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Epilobhim hirsutum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Epilobhim montan um, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherchia coli. See Osborn, 1943. Epilobhim parvtflorum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Epimedium aipinom, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Epimedium peraldlannm, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Epimedium pinna turn, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Eplmedhim youngianum v. niveom, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Epipactis latifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Epipactis tesselata, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Epiphyllum truncatum, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. episcleritis, clinical, see AUREOMYCIN. Equisetum arvense, a higher plant, aqueous extracts of the leaf and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other aqueous extracts of this plant are also ineffective against Staph, aureus and E. coli [2]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [3]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943; [3] Hayes, 1947. Equisetum telmateia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eragrostis cilianensis, a higher plant, aqueous extracts of which cause little or no inhibition when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phvtomonas tumefaciens. See Hayes, 1947.

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[113] Eranthemum cooperi, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eranthemum hypocrateriforme, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eranthemum nigritianum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eranthemum pulchellum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eranthemum wattil, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eranthis hyemalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eranthis sibirica, a higher plant, aqueous extracts of the root of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli [1], Other aqueous extracts of this plant are ineffective against both these microorganisms [2]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Ercilla voiubilis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eremascus fertilis, a fungus, the culture media of which are ineffective in vitro against Staphylococcus aureus. See C o o k and Lacey, 1945b. Erica arborea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Erica canaliculata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Erica carnea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Erica lusitanica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Erica mediterranea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Erigeroo acer, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Erigeron canadensis, a higher plant, extracts of which are effective in vitro against Mycobacterium tuberculosis but not against Staphylococcus aureus and Escherichia coli. See Gottshall et al., 1949. Erigeron philadelphicus, a higher plant, aqueous extracts of which are ineffective in vino against Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro aqueous extracts are reported to cause little or no inhibition of Staph, aureus, E. coli, Erwinia carotoxora, and Phytomonas tumefaciens [2], See [1] Osborn, 1943; [2] Hayes, 1947.

ERWINIA CAROTOVORA

Erigeron ramosus, a higher plant, aqueous extracts of the leaf, stem, and flower of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Erlobotrya japonica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eriobotrya prisnophylla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eriodictyon giutinosum, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Mycobacterium tuberculosis but not against Escherichia coli. See Gottshall et al., 1949. Eriogonum sobalpinum v. major, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli See Osborn, 1943. Eriosema grandiflomm, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Erlangea tomentosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Erodium chrysanthemum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Erodium circutarhim, a higher plant, various exextracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and in vivo against experimental malaria [2]. See [1] Osborn, 1943; [2] Spencer et al., 1947. Erodium hymenoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Erophila v e n u , a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eruca sativa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Erwinia amylovora, as test organism in vitro, see BACILLUS VULGATUS. F o r literature see Little and G r u b a u g h , 1946 (vegetables). Erwinia aroidae, as test organism in vitro, see BACILLUS VULGATUS; PENICILLIUM

PATULUM.

Erwinia carotovora, as test organism in

vitro,

s e e ACANTHOPYRUS s p . ; ACHILLEA MILLEFOLIU M ; A C O R U S CALAMUS; ACTINOMYCIN; A D I A N T U M PEDATUM; A E S C U L U S HIPPOCASTANUM; AGRIMONIA s p . ; A G R O S T E M M A GITHAGO; A L L I U M C E R N U M ; A L L I U M TRICOCCUM; A L L I U M VINEALE; AMBROSIA ARTEMISIIFOLIA; AMBROSIA TRIFIDA; A N E M O N E C A N A D E N S I S ; ANTENNARIA PARLINII; ANTENNARIA PLANTAGINIFOLIA; A P O C Y N U M CANNABINUM; ARABIS HIRSUTA; ARALIA SPINOSA; A R I S A E M A TRIPHYLLUM; A R U N C U S SYLVESTER; A S A R U M CANADENSE; A S C L E P I A S SYRIACA; ASCLEPIODORA VIRIDIS; A S I M I N A TRILOBA; ASPARAGUS OFFICINALIS; A S P I D I U M MARGINALE; BACILLUS VULGATUS; BARBAREA VULGARIS; B E L A M C A N D A C H I N E N S I S ; B E N Z O I N AESTIVALE; BERBERIS THUNBERGII; BLEPHILIA CILIATA; BOTKYCHIUM VIRGINIANUM; BUCHLOE DACTYLOIDES; C A M P T O S O R U S RHIZOPHYLLUS;

Cross references are indicated by SMALL CAPITALS

ERWINIA PHYTOPHTHORA

[114]

CAPSELLA BURSAPASTORIS; C A X D A M I N E BULBOSA; CARDAMINE PENNSYLVANICA; CARDUUS CRISPUS; CAREX STRICTA; CASTALIA TUBEROSA; CASTILLEJA COCCÍNEA; C A U L O P H Y L L U M THALICTROIDES; CELASTRUS SCANDENS; CERATOPHYLLUM DEMERSUM; C H A E R O P H Y L L U M PROCUMBENS; CHARA FOETIDA; CHENOPODIUM A L B U M ; C H I M A P H I L A MACULATA; CHRYSANTHEMUM L E U C A N T H E M U M ; C I B O T I U M SCHIEDEI; CICHORIUM INTYBUS; C I C U T A BULBIFERA; CICUTA MACULATA; C I M I C I F U G A RACEMOSA; CIRSIUM ARVENSE; CLADONIA RANGIFERINA; CONOCEPHAL U M CONICUM; CONVOLVULUS ARVENSIS; CRATAEGUS sp.; CREPIS BIENNIS; CROCUS VERNUS; C U N I L A ORIGANOIDES; CUSCUTA sp.; CYNOGLOSS U M VIRGINIANUM; C Y P E R U S PAPYRUS; C Y S T O P TERIS FRAGILIS; DACTYLIS GLOMERATA; DAUCUS CAROTA; DECODON VERTICILLATUS; DENTARIA LACINIATA; DIANTHERA AMERICANA; DICENTRA CANADENSIS; DIOSPYROS VIRGINIANA; DIPSACUS SYLVESTRIS; DODECATHERON MEADIA; ELEUSINE INDICA; EPIPACTIS TESSELATA; EQUISETUM ARVENSE; E R A G R O S T I S CILIANENSIS; ERIGERON PHILADELPHICUS; E R Y T H R O N I U M AMERICANUM; EUONYMUS OBOVATUS; E U P A T O R I U M PURPUREUM; EUPHORBIA CAROLLATA; GALINSOGA PARVIFLORA; G A L I U M APARINE; GAULTHERIA PROCUMBENS; G E R A N I U M M A C U L A T U M ; GEUM V E R N U M ; G I L L E N I A STIPULATA; G I N K G O BILOBA; HEDERÁ HELIX; HERACLEUM L A N A T U M ; H E U CHERA SANGUINEA; HEUCHERA VILLOSA; HIBISCUS MOSCHEUTOS; H l E R A C I U M VENOSUM; H o U S TONIA CAERULEA; H O U S T O N I A L O N G I F O L I A ; H Y D R O P H Y L L U M APPENDICULATUM; H Y P E R I C U M PERFORATUM; ILEX DECIDUA; ILEX OPACA; I M PATIENS P A L L I D A ; IODANTHUS PINNATIFIDUS; IRIS GERMANICA; J U N I P E R U S HORIZONTALS; LACTUCA CANADENSIS; L A M I U M PURPUREUM; LAPORTEA CANADENSIS; LEONURUS CARDIACA; L E P A C H Y S P I N N A T A ; L E P I D I U M CAMPESTRE; L E P I D I U M DRABA; L E P I D I U M VIRGINICUM; LIRIODENDRON TULIPIFERA; L I T H O S P E R M U M ARVENSE; L I T H O S P E R M U M C A N E S C E N S ; L Y C H N I S ALBA; LYCOPODIUM LUCIDULUM; L Y G O D I U M JAPONIC U M ; LYSIMACHIA N U M M U L A R I A ; LYSIMACHIA QUADRIFOLIA; M A L V A ROTUNDIFOLIA; MEDEOLA VIRGINIANA; MEDICAGO L U P U L I N A ; MELILOTUS ALBA; M E N Y A N T H E S TRIFOLIATA; N E P E T A HEDERACEA; NEPHROLEPSIS CARLIFOLIA; NEPHROLEPSIS EXALTATA V. B O S T O N I E N S I S ; OENOTHERA BIENNIS; OENOTHERA FRUTICOSA; ONOCLEA SENSIBILIS; O S M O R H I Z A CLAYTONI; OSMORHIZA LONGISTYLIS; O S M U N D A R E G A L I S ; OXALIS STRICTA; PAEONIA OFFICINALIS; P A N A X QUINQUEF O L I U M ; PASTINACA SATIVA; PEDICULARIS CANADENSIS; P É N I C I L L I U M P A T U L U M ; P E N T S T E M O N LAEVIGATUS; PHACELIA PURSHII; P H L O X DIVARICATA; PHYSOCARPUS OPULIFOLIUS; PICEA ABIES; P I N U S STROBUS; PLANTAGO LANCEOLATA; P L A N TAGO MAJOR; P L A T A N U S OCCIDENTALS; POA PRATENSIS; P O D O P H Y L L U M PELTATUM; POLEM O N I U M REPTANS; P O L Y G O N A T U M BIFLORUM; P O L Y G O N U M A M P H I B I U M ; P O L Y P O D I U M AUREUM; P O L Y P O D I U M LONGIFOLIUM; P O L Y P O D I U M POLYPODIOIDES; P O L Y P O D I U M VULGARE; P O L Y S T I C H U M ACROSTICHOIDES; P O L Y S T I C H U M LONCHITIS; POTAMOGETON CRISPUS; P O T A M O G E T O N NATANS; POTAMOGETON PECTINATUS; P o T E N T I L L A CANADENSIS; POTENTILLA RECTA; P R U N E L L A VULGARIS; P R U N U S PERSICA; P S I L O T U M N U D U M ; PSORALEA PEDUNCULATA; PTERIS AQUILINA; R A N U N C U L I ' S ABORTIVUS; R A N U N C U L U S SEPTENTRIONALIS; R H U S CANADENSIS; R U E L L I A CILIOSA; R U M E X ACETOSELLA; R U M E X CRISPUS; SAGITTARIA LATIFOLIA; SALVIA LYRATA; SALVINIA NATANS; S A M Cross

references

BUCUS CANADENSIS; SANGUINARIA CANADENSIS; SAPONARIA OFFICINALIS; SARRACENIA PURPUREA; SEDUM STOLONIFERUM; SELAGINELLA BRAUNII; SELAGINELLA K R A U S S I A N A ; SENECIO AUREUS; SIDA HERMAPHRODITA; SILENE VIRGINICA; S I L P H I U M PERFOLIATUM; S I L P H I U M TEREBINTHINAC E U M ; SMILACINA RACEMOSA; S M I L A C I N A STELLATA; S O L A N U M CAROLINENSE; S O L A N U M DULCAMARA; SPARTINA MICHAUXIANA; SPECULARIA PERFOLIATA; STELLARIA MEDIA; SYMPHORICARPOS ORBICULATUS; SYMPLOCARPUS FOETIDUS; T A R A XACUM OFFICINALE; T A X U S CANADENSIS; T H A L I C T R U M DIOICUM; TILLANDSIA USNEOIDES; TRAGOPOGON PRATENSIS; T R I F O L I U M HYBRIDUM; T R I FOLIUM PRATENSE; T R I F O L I U M REPENS; T R I L L I U M SESSILE; T Y P H A ANGUSTIFOLIA; U M B I L I CARIA DELINEATA; UVULARIA PERFOLIATA; V A L E RIANA P A U C I F L O R A ; VALERIANELLA RADIATA; VERBASCUM THAPSUS; VERBENA ANGUSTIFOLIA; VERONICA ARVENSIS; VERONICA OFFICINALIS; V I B U R N U M OPULUS; VICIA CRACCA; V I N C A MINOR; V I O L A PAPILIONACEA; V I T I S LABRUSCA; Y U C C A FILAMENTOSA; ZEBRINA PENDULA; Z I Z I A AUREA. F o r l i t e r a t u r e see L i t t l e a n d G r u b a u g h , 1946 (vegetables). E r w i n i a p b y t o p h t h o r a , as test o r g a n i s m in vitro, see BACILLUS VULGATUS; P E N I C I L L I U M P A T U L U M . E r w i n i a tracheiphila, as test o r g a n i s m in vitro, see ACTINOMYCIN. E r y n g i u m amesthystinnm, a h i g h e r p l a n t , e x t r a c t s o f w h i c h a r e i n e f f e c t i v e in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See G o t t s h a l l et al., 1949. Eryngium aquaticum, a higher plant, extracts o f w h i c h are i n e f f e c t i v e in vitro a g a i n s t Staphylococcus aureus, Escherichia coli, a n d Mycobacterium tuberculosis. S e e G o t t s h a l l e t al., 1949. Eryngium ebracteatum, a higher plant, aqueous e x t r a c t s o f w h i c h a r e i n e f f e c t i v e in vitro a g a i n s t Staphylococcus aureus a n d Escherichia coli. S e e O s b o r n , 1943. Eryngium foetidum, a higher plant, extracts o f w h i c h are e f f e c t i v e in t h e t r e a t m e n t o f e x p e r i m e n t a l m a l a r i a . S e e S p e n c e r et al., 1947. Eryngium yuccifolium, a higher plant, extracts o f which are slightly e f f e c t i v e in the treatment o f e x p e r i m e n t a l m a l a r i a . S e e S p e n c e r et al.. 1947. Erysimum murale, a higher plant, aqueous ext r a c t s o f w h i c h a r e e f f e c t i v e in vitro against Staphylococcus aureus a n d Escherichia coli. S e e O s b o r n , 1943. Erysimum perofskianum, a higher plant, aqueous e x t r a c t s o f the seeds o f w h i c h a r e e f f e c t i v e in vitro against Staphylococcus aureus and Escherichia coli. S e e O s b o r n , 1943. erysipelas, clinical, see AUREOMYCIN;

PENICILLIN.

Erysipelothrix m o n o c y t o g e n e s , as test o r g a n i s m in vitro, see MICROCOCCIN; NISIN. Erysipelothrix rhusiopathiae. 1 A s test o r g a n i s m in vitro, see A C T I N O M Y C I N ; L I C H E N I F O R M I N ; P O L Y M Y X I N S . 2 E x p e r i m e n t a l i n f e c t i o n s , see AUREOMYCIN; PENICILLIN. E r y t h r a e a beyrichii, a h i g h e r p l a n t , e x t r a c t s o f w h i c h are i n e f f e c t i v e a g a i n s t e x p e r i m e n t a l m a l a r i a . S e e S p e n c e r et al., 1947. E r y t h r a e a centaurhim, a h i g h e r p l a n t , e x t r a c t s o f w h i c h are i n e f f e c t i v e against e x p e r i m e n t a l m a l a r i a . S e e S p e n c e r et al., 1947. E r y t h r a e a chilensis, a h i g h e r p l a n t , e x t r a c t s o f w h i c h are ineffective against e x p e r i m e n t a l m a l a r i a . See S p e n c e r et al., 1947.

are i n d i c a t e d b y SMALL CAPITALS

[1151 E r y t h r a e a texense, a h i g h e r p l a n t , e x t r a c t s o f w h i c h a r e i n e f f e c t i v e against e x p e r i m e n t a l m a l a r i a . S e e S p e n c e r et al., 1947. E r y t h r a e a venusta, a h i g h e r p l a n t , e x t r a c t s o f w h i c h a r e slightly e f f e c t i v e i n the t r e a t m e n t o f e x p e r i m e n t a l m a l a r i a . S e e S p e n c e r et at., 1947. erythrin, an a n t i b a c t e r i a l s u b s t a n c e d e r i v e d f r o m r e d b l o o d cells. S e e W a k s m a n , 1947. S e e a l s o BLOOD. E r y t h r i n a sp., a h i g h e r p l a n t , c o n c e n t r a t e d a q u e o u s e x t r a c t s o f the C h i n e s e d r u g p r e p a r e d f r o m t h e b a r k o f w h i c h a r e e f f e c t i v e in vitro against Staphylococcus aureus b u t n o t against Escherichia coli. S e e G a w a n d W a n g , 1949. E r y t h r o c h i t o n braziliensis, a h i g h e r plant, a q u e o u s e x t r a c t s o f w h i c h a r e i n e f f e c t i v e in vitro a g a i n s t Staphylococcus aureus a n d Escherichia coli. S e e O s b o r n , 1943. Erythroninm americanum, a higher plant, the l e a v e s and flowers o f w h i c h in vitro inhibit Staphylococcus aureus, Escherichia coli, and Erwinia carotovora, but d o n o t inhibit Phytomonas tumejaciens. S e e H a y e s , 1947. E r y t h r o n h i m dens-canis, a h i g h e r plant, a q u e o u s e x t r a c t s o f the b u l b but n o t o f the l e a f o f w h i c h a r e e f f e c t i v e in vitro a g a i n s t Staphylococcus aureus a n d Escherichia coli. Neither of t h e s e e x t r a c t s inhibits the s p o r e s o f Neurospora crassa [1], O t h e r aqueous extracts o f t h i s p l a n t inhibit Staph, aureus and E. coli [ 2 ] , S e e [ 1 ] S c h n e l l a n d T h a y e r , 1949; [ 2 ] O s b o r n , 1943. E r y t h r o n i u m tuolmnensis, a h i g h e r plant, a q u e vitro o u s e x t r a c t s o f w h i c h a r e e f f e c t i v e in a g a i n s t Staphylococcus aureus a n d Escherichia coli. S e e O s b o r n , 1943. E r y t h r o x y l u m coca, a h i g h e r p l a n t , a q u e o u s e x t r a c t s o f w h i c h a r e i n e f f e c t i v e in vitro against Staphylococcus aureus a n d Escherichia coli. S e e O s b o r n , 1943. E r y t h r o x y l u m c o c a v . novogranatense, a h i g h e r p l a n t , a q u e o u s e x t r a c t s o f w h i c h are i n e f f e c t i v e in vitro against Staphylococcus aureus and Escherichia coli. S e e O s b o r n , 1943. E s c a l l o n i a langleyensis, a h i g h e r plant, a q u e o u s e x t r a c t s o f w h i c h are i n e f f e c t i v e in vitro against Staphylococcus aureus a n d Escherichia coli. S e e O s b o r n , 1943. E s c h e r i c h i a coll, a b a c t e r i u m , s o m e strains o f which (isolated f r o m Latin A m e r i c a n school c h i l d r e n ) a r e e f f e c t i v e in vitro against Shigella jlexneri a n d o t h e r Shig. s p p . Resistant o r g a n i s m s are v a r i o u s S a l m o n e l l a e , Neisseria catarrhalis, Vibrio comma, Klebsiella pneumoniae, Bacillus anthracis, Streptococcus fecalis, Staphylococcus albus, and s o m e Shig. spp. T h e a c t i v i t y is d e c r e a s e d b y h u m a n b l o o d and s e r u m b u t is r e l a t i v e l y t h e r m o s t a b l e . C r u d e s u p e r n a t a n t s f r o m s o m e strains o f E. coli inh i b i t i n o c u l a o f a b o u t 1,000 Shig. flexneri at 1:1,280-1:20,480 [1], O t h e r tests s h o w that this m i c r o o r g a n i s m p r o d u c e s a substance i n e f f e c t i v e in vitro against Actinomyces violaceus, A. aurantiacus, A. griseus, a n d A. globisporus [ 2 ] . Y e t o t h e r tests s h o w that it is i n e f f e c t i v e in i n h i b i t i n g the g r o w t h in vitro o f Ophiobolus graminis [3]. S e e [ 1 ] H a l b e r t , 1947; [ 2 ] K r a s s i l n i k o v and K o r e n i a k o , 1939; [ 3 ] B r o a d f o o t , 1933a and b . S e e a l s o COLICINE; COLICINS. A S test o r g a n i s m in vitro, see A B S I D I A GLAUCA; A C A N THOPYRUS sp.; ACTIDIONE; ACTINOMYCIN; ACTINORUBIN; ADIANTUM PEDATUM; AESCULUS HIPPOCASTANUM; A G R I M O N I A sp., AGROSTEMMA GITHAGO; ALLICIN; A L L I U M CEPA; ALLIUM

ESCHERICHIA

COLI

CERNUM; A L L I U M SATIVUM; A L L I U M SCHOENOPRASUM; A L L I U M TRICOCCUM; A L L I U M VINEALE; ALVEIN; A M B R O S I A ARTEMISIIFOLIA; AMBROSIA TRIFIDA; ANACARDIC ACID; A N E M O N E CANADENSIS; A N E M O N I N ; A N T E N N A R I A PARLINII; A N T E N NARIA PLANTAGINIFOLIA; ANTIBIOTIC 136; A N T I BIOTIC 3510; ANTIBIOTIC E h ; ANTIBIOTIC H - 3 ; ANTIBIOTIC " V " ; ANTIBIOTIC X G ; A P O C Y N U M CANNABINUM; ARABIS HIRSUTA; A R A L I A SPINOSA; A R C T I U M M I N U S AND ONOPORDON TAURICUM; A R I S A E M A TRIPHYLLUM; ARUNCUS SYLVESTER; A S A R U M CANADENSE v. REFLEXUM; ASCLEPIAS SYRIACA; A S C L E P I O D O R A VIRIDIS; A S I M I N A TRILOBA; ASPARAGUS OFFICINALIS; ASPERGILLIC ACID; ASPERGILLIN; ASPERGILLUS sp.; ASPERGILLUS CLAVATUS; ASPERGILLUS FLAVUS; ASPERGILLUS FUMARICUS; ASPERGILLUS F U M I GATUS; ASPERGILLUS GIGANTEUS; ASPERGILLUS GLAUCUS; ASPERGILLUS LUCHUENSIS; ASPERGILLUS NIDULANS; ASPERGILLUS NIGER; ASPERGILLUS NIGER-CITRICUS; ASPERGILLUS OCHRACEUS; A S P E R G I L L U S O R Y Z A E ; ASPERGILLUS RESTRICTUS; ASPERGILLUS SCHIEMANNI; A S P E R GILLUS SYDOWI; ASPERGILLUS TAMARII; A S P E R GILLUS TERREUS; A S P E R G I L L U S VERSICOLOR; ASPERGILLUS WENTII; ASPIDIUM MARGINALE; ASTASIA KLEBSEII; AUREOMYCIN; AYFIVIN; BACILIPIN A AND B ; BACILLIN; BACILLUS Sp.; BACILLUS LARVAE; BACILLUS LICHENIFORMIS; BACILLUS MESENTERICUS; BACILLUS VULGATUS; BACILYSIN; BACITRACIN; B A R B A R E A VULGARIS; BASIDIOBOLUS RANARUM; BELAMCANDA CHINENSIS; B F N 7 O I N AESTIVALE; BERBERIS THUNBERGII; BITORMIN; BIFORMINIC ACID; BIOCERIN; BLEPHILIA CILIATA; BLOOD; BORRELIDIN; BOTRYCHIUM VIRGINIANUM; BRASSICA NIGRA; BUCHLOE DACTYLOIDES; BUTTERCUP; CAMPTOSORUS RHIZOPHYLLUS; CAPSELLA BURSAPASTORIS; CARDAMINE BULBOSA; CARDAMINE P E N N S Y L V A N I A ; CARDUS CRISPUS; CAREX STRICTA; CASTALIA TUBEROSA; CASTILLEJA COCCINEA; C A U L O P H Y L L U M THALICTROIDES; C E L A S T R U S SCANDENS; CENTAUREA MACULOSA; C E R A T O P H Y L L U M DEMERSUM; C H A E R O P H Y L L U M P R O C U M B E N S ; CHAETOCLADIUM B R E F E L D I S ; CHAETOCLADIUM C L A T U M ; CHAETOMIN; CHARA FOETIDA; CHENOPODIUM ALBUM; CHILOMONAS PARAMECIUM; CHIMAPHILA MACULATA; CHLORAMPHENICOL; CHLORELL I N ; C H R Y S A N T H E M U M L E U C A N T H E M U M ; CIBOT I U M SCHIEDEI; C I C H O R I U M INTYBUS; C I C U T A BULBIFERA; CICUTA M A C U L A T A ; CIMICIFUGA RACEMOSA; CIRCULIN; C I R S I U M ARVENSE; CITRIN I N ; CLADONIA RANGIFERINA; CLAVACIN; CLITOCYBINES; CLOSTRIDIUM AEROFEOETIDUM; CLOSTRIDIUM BIFERMENTANS; CLOSTRIDIUM BOTUL I N U M ; CLOSTRIDIUM BUTYRICUM; CLOSTRIDIUM CENTROSPOROGENES; CLOSTRIDIUM C H A U V O E I ; CLOSTRIDIUM FALLAX; CLOSTRIDIUM FELSINEUS; C L O S T R I D I U M HISTOLYTICUM; CLOSTRIDIUM M U L T I F E R M E N T A N S T E N A L B U M ; CLOSTRIDIUM OEDEMATIENS; CLOSTRIDIUM PARASPOROGENES; CLOSTRIDIUM P U T R I F I C U M ; CLOSTRIDIUM SEPT I C U M ; CLOSTRIDIUM SORDELLII; CLOSTRIDIUM SPOROGENES; CLOSTRIDIUM T E R T I U M ; CLOSTRIDIUM TETANI; CLOSTRIDIUM TETANOMORPHUM; C L O S T R I D I U M WELCHII; COLICINE; COLICINS; COLISTATIN; C O N O C E P H A L U M CONICUM; C O N VULVULUS ARVENSIS; C o P T I S CHINENSIS; C O R T I NARIUS ROTUNDISPORUS; CRATAEGUS Sp.; CREPIS BIENNIS; C R O C U S VERNUS; CUNILA ORIGANOIDES; CUNNINGHAMELLA ECHINULATA; C U N N I N G H A M E L L A ELEGANS; CUSCUTA s p . ; CYNOGLOSSUM VIRGINIANUM; CYPERUS PAPYRUS; CYSTOPTERIS FRAGILIS; D A C T Y L I S GLOMERATA; DAUCUS CAROTA; D E C O N D O N VERTICILLATUS;

C r o s s r e f e r e n c e s are i n d i c a t e d b y SMALL CAPITALS

ESCHERICHIA

C O U

[116]

DENTARIA LACINIATA; DIANTHERA AMERICANA; DICENTRA CANADENSIS; DICOUMARIN; DIOSPYRUS VIRGIN [AN A; DIPLOCOCCIN; DIPSACUS SYLVESTRIS; DODECATHERON MEADU; E L E U S I N E INDICA; ENNLATIN; EPIDERMOPHYTON FLOCCOSUM; EPIPACTIS TESSELATA; E Q U I S E T U M ARVENSE; ERAGROSTIS CILIANENSIS; ERICERON PHILADELPHICUS; E R Y T H R O N I U M AMERICANUM; EUGLENA GRACILIS; E U P A T O R I U M PURPUREUM; EUPHORBIA COROLLATA; E U O N Y M U S OBOVATUS; F O M E S OFFICINALIS; FRADICIN; FREQUENTIC ACID; FUMIGACIN; FUSCIN; GALINSOGA P A R V I F L O R A ; GALIUM APARINE; GAULTHERIA PROCUMBENS; GEODIN; G E R A N I U M MACULATUM; G E U M VERNUM; G I L LENIA STIPULATA; G I N K G O BILOBA; GLADIOLIC ACID; GLIOTOXIN; G L U T I N O S I N ; GRAMICIDIN; GRAMICIDIN S ; GRISEIN; HANSENULA ANOMALA; HEART; HEDERÁ HELIX; HERACLEUM LANATUM; HEUCHERA SANGUINEA; HEUCHERA VILLOSA; H I BISCUS MOSCHEUTOS; HIERACIUM VENOSUM; HIRSUTIC ACIDS; HOUSTONIA CAERULEA; H O U S TONIA LONGIFOLIA; HYDROSPHYLLUM APPENDICULATUM; H Y P E R I C U M PERFORATUM; ILEX DECIDUA; ILEX OPACA; I M P A T I E N S PALLIDA; INULA SPIRAEIFOLIA; IODANTHUS PINNATIFIDUS; IODININ; IPOMOEA BATATAS; IRIS GERMANICA; JAVANICIN; KOJIC ACID; KRIGIA AMPLEXICAULIS; LACHNEA CRETEA; LACTUCA CANADENSIS; L A M I U M P U R P U R E U M ; LAPORTEA CANADENSIS; LATEROSPORIN A AND B ; LAVENDULIN; LEONURUS CARDIACA; LEPACHYS PINNATA; L E P I D I U M CAMPESTRE; LEPIDIUM DRABA; LEPIDIUM VIRGINIC U M ; LEPTOTAENIA D I S S E C T A ; LEPTOTAENIA MULTIFEDA; LICHENIFORMIN; LIRIODENDRON TULIPIFERA; L I T H O S P E R M U M ARVENSE; LITHOSPERM U M CANESCENS; LITMOCIDIN; LUPULON AND H U M U L O N ; LYCHNIS ALBA; LYCOPERSICUM P I M PINELLIFOLIUM; LYCOPODIUM LUCIDULUM; L Y GODIUM J A P O N I C U M ; LYSIMACHIA NUMMULARIA; LYSIMACHIA QUADRIFOLIA; MALVA ROTUNDIFOLIA; MEDEOLA VIRGINIANA; MEDICAGO LUPULINA; M E L I L O T U S ALBA; M E N Y A N T H E S TRIFOLIATA; 2 - M E T H O X Y - I , 4-NAPHTHOQUINONE; 5-METHOXYP-TOLUQUINONE; MICROCOCCIN; MICROMONOSPORIN; MUSARIN; M U S A SAPIENTUM; MYCETIN; MYCOPHENOLIC ACID; MYCOSUBTILIN; NEOMYCIN; N E P E T A HEDERACEA; NEPHROLEPIS CARDIFOLIA; NEPHROLEPIS EXALTATA V. BOSTONIENSIS; NIDULINE; NOCARDIA GARDNERI; NOCARDIN; NOTALYSIN; NUDIC ACID A AND B ; OENOTHERA BIENNIS; OENOTHERA F R U T I C O S A ; ONOCLEA SENSIBIUS; OSMORHIZA CLAYTONI; OSMORHIZA LONGISTYLIS; OSMUNDA REGALIS; OXALIS STRICTA; PAEONIA OFFICINALIS; PANAX QUINQUEFOL I U M ; PASTINACA SATIVA; PEDICULARIS CANADENSIS; PENATIN; PENICILLIC ACID; PENICILLIN; P É N I C I L L I U M EXPANSUM ( ? ) ; PÉNICILLIUM PAT U L U M ; P E N T S T E M O N LAEVIGATUS; PERSOONIA PINIFOLIUS; PHACELIA PURSHII; PHLOX DIVARICATA; PHYCOMYCES; PHTHIOCOL; PHYSOCARPUS OPULIFOLIUS; PICEA ABIES; P I N U S STROBUS; P L A N T A G O LANCEOLATA; P L A N T A G O MAJOR; PLATANUS OCCIDENTALIS; PLEUROTIN; POA PRATENSIS; PODOPHYLLUM PELTATUM; P O L E M O N I U M REPTANS; POLYGONATUM BIFLORUM; POLYG O N U M AMPHIBIUM; POLYMYXINS; POLYPEPTIN; POLYPODIUM AUREUM; POLYPODIUM LONGIFOLIU M ; POLYPODIUM POLYPODIOIDES; POLYPODIUM VULGARE; POLYPORIN; POLYPORUS CINNABARIN U S ; POLYSTICHUM ACROSTICHOIDES; POLYSTICHUM LONCHITIS; POTAMEGETON CRISPUS; POTAMOGETON NATANS; POTAMOGETON PECTINATUS; POTENTILLA CANADENSIS; POTENTILIA RECTA; PROACTINOMYCIN; PROTAMINE ZINC INSULIN; PRUNELLA VULGARIS; P R U N U S PERSICA; PSALLIOTA XANTHODERMA; PSEUDOMONAS AE-

RUGINOSA; PSEUDOMONAS FLUORESCENS; P S E U DOMONAS PUTIDA; P S I L O T U M NUDUM; PSORALEA PEDUNCULATA; PTERIS AQUILINA; PTERYGOSPERMIN; PUCHIIN; PUROTHIONIN; PYO COMPOUNDS; PYOCYANIN; QUERCETIN; RANUNCULUS ABORTIVUS; R A N U N C U L U S SEPTENTRIONALIS; RAPHANIN; RHEIN; R H E U M RHAPONTICUM; R H U S CANADENSIS; R H U S HIRTA; RIBES VULGARE; R I PORIA LABRUSCA; RUELLIA CILIOSA; RUMEX ACETOSELLA; R U M E X CRISPUS; SAGITTARIA LATIFOLIA; SALVIA LYRATA; SALVINIA NATANS; SAMBUCUS CANADENSIS; SANGUINARIA CANADENSIS; SAPONARIA OFFICINALIS; SARRACENIA PURPUREA; SEDUM STOLONIFERUM; SELAGINELLA BRAUNII; SELAGINELLA KRAUSSIANA; S E N E C I O AUREUS; SIDA HERMAPHRODITA; SILENE VIRGINICA; SILPHIUM PERFOLIATUM; SILPHIUM TEREBINTHINAC E U M ; SMILACINA RACEMOSA; SMILACINA STELLATA; S O L A N I N E ; S O L A N U M CAROLINENSE; SOLANUM DULCAMARA; SPARTINA MICHAUXIANA; SPECULARIA PERFOLIATA; SPINULOSIN; SPIRAEA ARUNCUS; STAPHYLOCOCCUS; STAPHYLOCOCCUS AUREUS; STELLARIA MEDIA; STREPTIN; STREPTOLIN; STREPTOMYCES ANTIBIOTICUS; STREPTOMYCES AURANTIACUS; STREPTOMYCES AUREOFACIENS; STREPTOMYCES GLOBIGII; STREPTOMYCES GRISEUS; STREPTOMYCES LAVENDULAE; STREPTOMYCES VENEZUELAE; STREPTOMYCES VIOLACEUS; STREPTOMYCIN; STREPTOSTASIN; STREPTOTHRICIN; STREPTOTHRICIN V I ; STREPTOTHRIX; SUBTENOLIN; SUBTILIN; SUBTILYSINE; SYMPHORICARPOS ORBICULATUS; SYMPLOCARPUS FOETIDUS; TARAXACUM O F F I C I N A L E ; T A R D I N ; TAXUS CANADENSIS; TERRAMYCIN; TETRAHYMENA GALEII; TETRAHYMENA VORAX; THALICTRUM DIOICUM; T H U J A PLICATA; THYROID; TILLANDSIA USNEOIDES; TRAGOPOGON PRATENSIS; TRAMETES S E R P E N S ; TRICHOPHYTON MENTAGROPHYTES; TRICHOPHYTON TONSURANS; TRICHOPHYTON VIOLACEUM; TRICHOTHECIN; TRIFOLIUM HYBRIDUM; TRIFOLIUM PRATENSE; TRIFOLIUM REPENS; TRILLIUM SESSILE; TRYPANOTOXIN; TYPHA ANGUSTIFOLIA; TYROCIDINE; TYROTHRICIN; U M BILICARIA D E L I N E A T A ; USNIC ACID; USTIN; UVULARIA PERFOLIATA; VALERIANA PAUCIFLORA; VALERIANELLA RADIATA; VERBASCUM THAPSUS; VERBENA ANGUSTIFOLIA; VERONICA ARVENSIS; VERONICA OFFICINALIS; V I B U R N U M OPULUS; VICIA CRACCA; VINCA MINOR; VIOLA PAPILIONACEA; V I T I S LABRUSCA; WHEAT BRAN; XANTHOMYCINS A AND B ; YUCCA FILAMENTOSA; ZEBRINA PENDULA; ZIZIA AUREA. F o r l i t e r a t u r e

concerning Escherichia coli see the following: Arnstein et al., 1946a ( F u s a r i a ) ; Burkholder and Evans, 1945 (lichens); Burkholder et al., 1944 (lichens); C a r d o s o and Santos, 1948 (higher plants); Carlson and Douglas, 1948a ( h i g h e r p l a n t s ) ; Carlson, Douglas, and Robertson, 1948 (higher plants); Carpenter, 1945 ( f u n g i ) ; Cook and Lacey, 1945b ( f u n g i ) ; Gaw and Wang, 1949 (higher p l a n t s ) ; Gill-Carey, 1949a (Aspergilli); Gottshall et al., 1949 (higher plants); Hervey, 1947 ( f u n g i ) ; Little and G r u b a u g h , 1946 (vegetables); Lucas and Lewis, 1944 (higher p l a n t s ) ; Mathieson, 1946 ( f u n g i ) ; Osborn, 1943 (higher p l a n t s ) ; Robbins et al., 1945 ( f u n g i ) ; Sanchez et al., 1948 ( w o o d s ) ; Sanders et al., 1945 (higher plants); Schnell and Thayer, 1949 (higher plants); Wilkins, 1946a ( f u n g i ) ; Wilkins, 1946b ( f u n g i ) ; Wilkins, 1947a ( f u n gi); Wilkins, 1947b ( f u n g i ) ; Wilkins, 1947c ( f u n g i ) ; Wilkins, 1948 ( f u n g i ) ; Wilkins and Harris, 1942 ( f u n g i ) ; W i l k i n s a n d Harris, 1943a ( f u n g i ) ; Wilkins and Harris, 1944a ( f u n g i ) ; Wilkins and Harris, 1944d ( f u n g i ) .

Cross references are indicated by SMALL CAPITALS

[117] Escherichia coli factor, see PENATIN. Eschscholtzia californica, a higher plant, aqueous extracts of the seed of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Other aqueous extracts of this plant are also ineffective against these two microorganisms [2]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Euadenta eminens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eucalyptus sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Eucalyptus exlmia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eucalyptus fasciculata, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi [1,2]. See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Eucalyptus globulus, a higher plant, some extracts of which are effective in vitro against Mycobacterium tuberculosis but not against Staphylococcus aureus and Escherichia coli [1]. Other extracts inhibit Staph, aureus but not E. coli [2]. Still other extracts are ineffective in the treatment of experimental malaria [3], See [11 Gottshall et al., 1949; [2] Osborn, 1943; [3] Spencer et al., 1947. Eucalyptus haemostoma, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Eucalyptus lehmannil, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi [1,2], See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Eucalyptus leucoxylon, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi [1,2]. See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Eucalyptus leucoxylon v. macrocarpa, a higher plant, extracts of which are effective in vitro against Staphylococus aureus but not against Salmonella typhi [1,2], See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Eucalyptus megacarpa, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi [1,2]. See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Eucalyptus piperita, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Eucalyptus sepulcralls, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi [1,2]. See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Eucalyptus viminalis, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Eucomis punctata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Ösborn, 1943.

EUONYMUS ATROPURPUREUS

Eucommis ulmoides, a higher plant, concentrated aqueous extracts of the Chinese drug prepared f r o m the bark of which are ineffective in vitro against Staphylococus aureus and Escherichia coli. See Gaw and Wang, 1949. Eucryphia billardieri, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eugenia caryophyllata, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Eugenia edulis, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Eugenia myrtifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eugenia ovata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eugenia uniflora, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Euglena spp., as test organisms in vitro, see RANUNCULUS

OCCIDENTALIS.

Euglena gracilis, a Protozoon, lysates of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Mycobacterium phlei, and Myco, tuberculosis hominis. See McKee et al., 1947. eumycin, an antibiotic substance derived f r o m a strain of Bacillus subtilis. It is extracted from the culture media by precipitation with acid and is then re-extracted with ethanol. The residue left after evaporation of the alcohol solution is redissolved in dilute sodium hydroxide and filtered through a Berkefeld filter. The active material is soluble in ethanol, butanol, and acetone, and insoluble in ether and amyl acetate. It is heat stable in acid and unstable in alkaline solutions beyond p H 8.0 [1], Eumycin is very similar to bacillomycin [2]. Eumycin is without effect in vitro on Salmonella typhi, colon bacilli, Monilia, and Cryptococcus and is o n l y s l i g h t l y effective against staphylococci [1], I n concentrations of 0.1-0.3 m g / c c it inhibits the following [1]: Actinomyces spp. Epidermophyton floccosum Hormodendrum spp. Microsporum gypseum Mycobacterium tuberculosis avium Mycobacterium tuberculosis hominis Sporotrichum spp. Trichophyton mentagrophytes Corynebacterium diphtheriae is inhibited by 0.005 m g / c c [1]. Eumycin has a low toxicity for mice [1]. See [1] Johnson and Burdon, 1946; [2] Landy et al., 1948. Euonymus alatus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Euonymus atropurpureus, a higher plant, various extracts of which are ineffective in vitro against Bacillus subtilis [1], Escherichia coli [1,2], Staphylococcus aureus [2], and Mycobacterium tuberculosis [2], See [1] Sanders et al., 1945; [2] Gottshall et al., 1949.

Cross references are indicated by SMALL CAPITALS

EUONYMUS NANA

[11»]

Eaonjranu nana v. koopmannii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eoonymos obovatus, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Eoonymos pendulos, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eupatorhim altissimom, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Eupatorhim araliaefoUiim, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eupatorhim rannabinom, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eapatoriom capillifollum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Eapatoriom Ugnstrinum, a higher plant, extracts of the stems and leaves of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Eapatoriom marglnata, a higher plant, aqueous extracts of the seed and seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of NeuroSpora crassa. See Schnell and Thayer, 1949. Eopatorhim perfoliatum, a higher plant, various extracts of which are effective in vitro against Staphylococcus aureus [1] but not against Escherichia coli [1, 2] and Bacillus subtilis [2]. Aqueous and ether extracts of the flower, leaf, stem, and root are ineffective against Staph, aureus, E. coli, and the spores of Neurospora crassa [3]. See [1] Carlson, Douglas, and Robertson, 1948; [2] Sanders et al., 1945; [3] Schnell and Thayer, 1949. Eapatoriom purpureum, a higher plant, various extracts of which are effective in vitro against Staphylococcus aureus [1], Escherichia coli [1,2], and Bacillus subtilis [2], Aqueous and ether extracts of the flower, leaf, and stem are ineffective against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [3]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [4], See [1] Carlson, Douglas, and Robertson, 1948; [2] Sanders et al., 1945; [3] Schnell and Thayer, 1949; [4] Hayes, 1947. Eupatorhim pnrposU, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eapatoriom ripariom, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eupatorium rotundifolhim, a higher plant, extracts of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947.

Eopatorinm urtkaefoliom, a higher plant, some extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli [1] and other extracts of which are ineffective against these microorganisms [2]. See [1] Carlson, Douglas, and Robertson, 1948; [21 Osborn, 1943. Eopatorhim verbenaefolhim, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Euphorbia characias, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Euphorbia corollata, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Eophorbia cotinoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Euphorbia fulgens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eophorbia helioscopia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Euphorbia heterophylla, a higher plant, extracts of which are effective in vitro against Mycobacterium tuberculosis but not against Staphylococcus aureus and Escherichia coli. See Gottshall et al., 1949. Euphorbia hislopil, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Euphorbia maculata, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Euphorbia marglnata, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Euphorbia myrsinites, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Euphorbia pekinensis, a higher plant, concentrated aqueous extracts of the Chinese drug prepared from the root of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Gaw and Wang, 1949. Euphorbia peplus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Euphorbia pilullfera, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Euphorbia pulcherrima, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Euphorbia supina, a higher plant, extracts of which are effective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945.

Cross references are indicated by

S M A L L CAPITALS

[119]

FICUS B E N J A M I N A

Euphorbia tirucalli, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Euphorbia variegata, a higher plant, extracts of which are effective in vitro against Mycobacterium tuberculosis but not against Staphylococcus aureus and Escherichia coli. See Gottshall et al., 1949. Euphorbia wulfenii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Euphrasia officinalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eupomatia bennettii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Eurotia lanata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Eustoma russellianum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Eutaxia myrtifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Evernia vulpina, a lichen, extracts of which are effective in vitro against Staphylococcus aureus a n d / o r Bacillus subtilis. See Burkholder and Evans, 1945. Evodia eiegans v. ridleyii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Evodia micrococca, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Evodia Schüller! v. ridleyii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Evolvulus arizonicus, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Exacum affine, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Excoecaria bicolor, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Exidia glandulosa, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2]. See [1] Robbins et al., [2] Wilkins and Harris, 1944d. Exidia nucleata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Exochorda macrantha, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Exostema caribaeum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. expansin, see CLAVACIN.

Fagelia hyssopifolia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Fagopynim esculentum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Fagraea zeylanica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Fagns syivatica, a tree, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and extracts of the litter of which are ineffective against Staph, aureus [2], See [1] Osborn, 1943; [2] Melin and Wiken, 1946. Fatiia japonica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Faujasia flexuosa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Faurea macnaughtonia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Favoius canadensis, a fungus, which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3]. See [1] Hervey,

1947; [2] Robbins et al., 1945; [3] Wilkins, 1947b. Feijoa sellowiana v. variegata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Felicia bergeriana, a higher plant, extracts of the seed of which are effective in vitro against the spores of Neurospora crassa, while aqueous extracts of the seedling, flower, leaf, stem, and root are ineffective. None of these extracts inhibits Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Femsjonia luteoalba, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Ferula thyrsifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Festuca pratensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ficus artocarpoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ficus benjamina, a higher plant, aqueous extracts of which are ineffective in vitro against

Cross references are indicated by SMALL CAPITALS

FICUS CARICA

[120]

Staphylococcus aureus and Escherichia coli. See Osborn, 1943. F k o s carica, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Ficus dWeratfolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ficus erecta, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ficus macrophylia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ficus radicaos, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ficus stipulata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. FiUcfum decipiens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Filipéndula hexapetala, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Filipéndula ulmarla, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. fish. Extracts from the tissues of fish are reported as possessing antibacterial activity. See Pavan, 1949. Fistulina hepatica, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not Escherichia coli [1] and b) to be ineffective against these two microorganisms [2, 3]. Extracts of the sporophores of this fungus inhibit Staph, aureus but not E. coli and Pseudomonas aeruginosa [4], See [1] Robbins et al., 1945; [2] Wilkins, 1946b; [3] Wilkins, 1948; [4] Wilkins and Harris, 1944d. Fittonia verschaffeltii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Flacourtia cataphracta, a higher plant, aqueous extracts of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus. See Osborn, 1943. Flacourtia ramoutchi, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Flammula alnicola, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2]. The fungus is also reported to be weakly inhibitory for Staph, aureus and/or F.. coli [3], See [1] Robbins et al., 1945; [2] Wilkins and Harris, 1944d; [3] Wilkins, 1947b. Flammula californica v. communis, a fungus, extracts of the sporophores of which are in-

effective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Flammula carbonaria, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [3]. See [1] Hervey, 1947; [2] Wilkins, 1948; [3] Wilkins and Harris, 1944d. Flammula excentrka, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Flammula excentrka v. macro spo ra, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Flammula fomentarhis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Flammula fusus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Flammula gummosa, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [3], See [1] Hervey, 1947; [2] Wilkins, 1947c; [3] Wilkins and Harris, 1944d. Flammula hybrida, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Flammula lenta, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Wilkins, 1947c; [2] Wilkins and Harris, 1944d. Flammula lubrica, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coll, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Flammula ochroleuca, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Hervey, 1947; [2] Wilkins and Harris, 1944d. Flammula penetrans, a fungus which is weakly inhibitory in vitro for Staphylococcus aureus and/or Escherichia coli. See Wilkins, 1948. Flammula purpurata, a fungus which is weakly inhibitory in vitro for Staphylococcus aureus and/or Escherichia coli. See Wilkins, 1947b. Flammula saplnea, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be weakly inhibitory for Staph, aureus and /or E. coli [2], Extracts of the sporophores of this fungus inhibit Staph, aureus but not E. coli and Pseudomonas aeruginosa [3], See [1] Hervey, 1947; [2] Wilkins, 1948; [3] Wilkins and Harris, 1944d. Flammula tricholoma, a fungus, extracts of the sporophores of which are ineffective in vitro

Cross references are indicated by SMALL CAPITALS

FÛMES IGNIARIUS

[121] against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. flavicin, an antibiotic substance similar to or identical with penicillin F [1] produced by Aspergillus flavus [2], It is also known as flavacidin [3], See [1] Fried et al., 1946; [2] Bush and Goth, 1943; [3] McK.ee et al., 1944. Flavobacterium spp., as test organisms in vitro, s e e ACTINOMYCIN;

BACITRACIN.

Flotovia excelsa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Foeniculum vulgare, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [2]. Aqueous extracts of the seedling of this plant are also ineffective against Staph, aureus, E. coli, and the spores of Neurospora crassa [3]. See [1] Osborn, 1943; [2] Gottshall et al., 1949; [3] Schnell and Thayer, 1949. Fomes sp., a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Fomes annosus, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and/or Escherichia coli [1] and b) to inhibit both these microorganisms [2, 3, 4], Extracts of the sporophores of this fungus are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [5]. T h e c u l t u r e media inhibit Staph, aureus in vitro at 1:128 [3], See [1] Wilkins, 1946b; [2] Robbins et al., 1945; [3] Hervey, 1947; [4] Wilkins, 1948; [5] Wilkins and Harris, 1944d. As test organism in vitro, s e e GLIOTOXIN; LARIX DECIDUA; QUOIA SEMPERVIRENS; T H U J A PLICATA.

SE-

Fomes applanatus, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2]. It is also reported to be ineffective against these organisms [3]. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1947b. Fomes calklnsii, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3]. See [1] Hervey, 1947; [2] Wilkins, 1948; [3] Robbins et al., 1945. Fomes clelandl, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], and b) to inhibit Staph, aureus but not E. coli [3]. See [1] Wilkins, 1947a; [2] Wilkins, 1948; [3] Robbins et al., 1945. Fomes conchatus, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], and b) to inhibit Staph, aureus but not E. coli [3]. See [1] Hervey, 1947; [2] Wilkins, 1947a; [3] Robbins et al., 1945. Fomes connatiis, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2]. See [1] Hervey, 1947; [2] Robbins et al., 1945. Fomes cryptarum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Fomes densus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Fomes elUsianus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947.

Fomes everhartii, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3], See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1948. Fomes extensas, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2] and b) to inhibit Staph, aureus but not E. coli [3], See [1] Hervey, 1947; [2] Wilkins, 1948; [3] Robbins et al., 1945. Fomes fastaosos, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Fomes ferruginosos, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1], and b) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [2, 3], Extracts of the sporophores of this fungus are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [4], See [1] Robbins et al., 1945; [2] Wilkins, 1946b; [3] Wilkins, 1948; [4] Wilkins and Harris, 1944d. Fomes fomentarius, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3], The culture media of this fungus are weakly inhibitory for Staph, aureus and/or E. coli [4]. Extracts of the sporophores are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [5]. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1948; [4] Wilkins, 1947a; [5] Wilkins and Harris, 1944d. Fomes fraxlneus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3], Extracts of the sporophores of this fungus are also ineffective against these two microorganisms [4], See [1] Robbins et al., 1945: [2] Hervey, 1947; [3] Wilkins, 1946b; [4] Wilkins, 1946a. Fomes fraxinophUus, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2] and b) to be ineffective against these two microorganisms [3]. The culture medium inhibits Staph. aureus but not E. coli. [4]. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1948; [4] Wilkins, 1947b. As test org a n i s m in vitro

see ACTINOMYCES ANNULATUS;

A C T I N O M Y C E S FLAVOVIRENS; A C T I N O M Y C E S GOUGEROTI; A C T I N O M Y C E S HALSTEDII; A C T I N O M Y C E S MADURAE; A C T I N O M Y C E S VIRIDOCHROMOGENUS.

For literature, see Alexopoulos and Herrick, 1942 (actinomycetes). Fomes fulvus, a fungus which is reported a) to be weakly inhibitory in vitro for Staphylococcus aureus and/or Escherichia coli [1], b) to inhibit Staph, aureus but not E. coli [2], and c) to inhibit both these microorganisms [3], See [1] Wilkins, 1948; [2] Hervey, 1947; [3] Robbins et al., 1945. Fomes geotropus, a fungus which is reported

a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2J and b) to inhibit Staph, aureus but not E. coli [3]. See [1] Wilkins, 1946b; [2] Hervey, 1947; [3] Robbins et al., 1945. Fomes hemitephnis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Fomes igniarius, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3, 4]. The culture media of this fungus are weakly inhibitory for Staph.

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

F O M E S IGN1ARIUS

[1221

aureus and E. coli [4], Extracts of the sporophores are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [5], See [I] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1948; [4] Wilkins, 1947a; [5] Wilkins and Harris, 1944d. Fomes igniarius v. laevigatas, a fungus, which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2]. See [1] Hervey, 1947; [2] Robbins et al., 1945. Fomes igniarias v. popalinns, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Robbins et al., 1945. Fomes igniarius robastns, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Fomes junlperinns, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3J. The liquid culture medium of this fungus inhibits Staph, aureus in dilutions no greater than 1:64 [3], See [1] Hervey, 1947; [2] Wilkins, 1948; [3] Robbins et al., 1945. Fomes lignosus, a fungus which is effective in vitro against Staphylococcus aureus and/or Escherichia coli. See Wilkins, 1946b. Fomes lividus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947a. Fomes lobatus, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b ) to be ineffective against these two microorganisms [2]. See [1] Robbins et al., 1945; [2] Hervey, 1947. Fomes marmoratus, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be ineffective against these two microorganisms [2, 3]. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1946b. Fomes melanosporus, a fungus, the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus and/or Escherichia coli. See Wilkins, 1947a. Fomes meliae, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2] and b) to inhibit these microorganisms [3, 4], Investigators state that this antibacterial activity may be due to the production of acid [3, 4], See [1] Wilkins, 1948; [2] Wilkins, 1947b; [3] Robbins et al., 1945; [4] Hervey, 1947. Fomes nigricans, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Fomes nigrollmitatus, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Fomes noxhis, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2]. See [1] Hervey, 1947; [2] Wilkins, 1946b. Fomes officinalis, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3]. This antibacterial activity may be due to the production of acid [1, 2]. The culture media of this fungus are strongly inhibitory for Staph, aureus and/or E. coli [4], Extracts of the fruiting bodies are ineffective against Staph, aureus and E. coli, while extracts of the mycelia inhibit these microorganisms at dilutions of 1:10-1:500 [5],

See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1947b; [4] Wilkins, 1947a; [5] Borzini, 1947. Fomes pachyphioens, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Fomes pini, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], This antibacterial activity may be due to the production of acid [1]. The fungus is also reported to inhibit Staph, aureus and/or E. coli (3]. See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1947b. Fomes pini v. abietis, a fungus which is reported a) to be weakly inhibitory in vitro for Staphylococcus aureus and /or Escherichia coli [1] and b) to inhibit both these microorganisms [2], This antibiotic action may be due to the production of acid [2], The fungus is also reported to be ineffective against Staph, aureus and E. coli [3]. See [1] Wilkins, 1948; [2] Robbins et al., 1945; [3] Wilkins, 1947b. Fomes pinicola, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. This antibacterial activity may be due to the production of acid [1, 2], The culture media of this fungus are weakly inhibitory for Staph, aureus and E. coli [3]. See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1947a. Fomes pomaceus, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], and b) to inhibit both these microorganisms [3]. See [1] Wilkins, 1946b; [2] Wilkins, 1948; [3] Robbins et al., 1945. Fomes rentformis, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Fomes rlbis, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and b) to inhibit both these microorganisms [2, 3]. The liquid culture medium of this fungus inhibits Staph, aureus in dilutions no greater than 1:64 [3], See [1] Wilkins, 1946b; [2] Hervey, 1947; [3] Robbins et al., 1945. Fomes rimosus, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2] and b) to inhibit Staph, aureus but not E. coli [3], See [1] Wilkins, 1948; [2] Hervey, 1947; [3] Robbins et al., 1945. Foines robiniae, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Fomes robustus, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2] and b) to inhibit Staph, aureus but not E. coli [3]. See [1] Hervev, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1948. Fomes robustus v. pinuum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Fomes robustus v. tsugina, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3], See [1] Wilkins, 1948; [2) Hervey, 1947; [31 Robbins et al., 1945. Fomes roseus, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2]. The culture media of this fungus are weakly inhibitory for Staph, aureus

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[ 123 ] and/or E. coli [3], See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1947a. Fomes rabustus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947a. Fomes rudis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Fomes salicinus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Fomes scutellatus, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be ineffective against these two microorganisms [2, 3]. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1947b. Fomes spadiceus, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be ineffective against these two microorganisms [2]. See [1] Hervey, 1947; [2] Wilkins, 1948. Fomes subroseus, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1], b) to be weakly inhibitory for Staph, aureus and/or E. coli [2, 3], and c) to inhibit both these microorganisms [4], This antibiotic activity may be due 10 the production of acid [4]. See [1] Hervey, 1947; [2] Wilkins, 1948; [3] Wilkins, 1947b; [4] Robbins et al., 1945. Fomes tenuis, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be ineffective against these two microorganisms [2, 3]. See [1] Robbins et al., 1945; [2] Wilkins, 1948; [3] Wilkins, 1947b. Fomes torulosus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], See [1] Wilkins, 1948; [2] Robbins et al., 1945. Fomes tricolor, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947b. Fomes ulmarius, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and b) to inhibit these microorganisms [2]. This antibacterial activity may be due to the production of acid [2]. Extracts of the sporophores of this fungus are ineffective in vitro against Staph, aureus, E. coli, and Pseudomonas aeruginosa [3], See [1] Wilkins, 1946b; [2] Robbins et al., 1945; [3] Wilkins and Harris, 1944d. Fomes ungulatus, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. This antibiotic action may be due to the production of acid [1]. The fungus is also reported to inhibit Staph, aureus and/or E. coli [2], See [1] Robbins et al., 1945; [2] Wilkins, 1947b. Fomes vinosus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947a. Fomitiporia dryophlla, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Fomitiporia earleae, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947.

FRAGARIA «ROYAL SOVEREIGN"

Fomitiporia flavomarginata, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Forsythia giraldiaiia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Forsythia intermedia v. spectabilis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Forsythia ovata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Forsythia suspensa, a higher plant, concentrated aqueous extracts of the Chinese drug prepared from the fruit of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See G aw and Wang, 1949. Forsythia viridissima, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Fothergilla major, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Fothergilla monticola, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. fradicin, an antibiotic produced by Streptomyces jradiae. It can be obtained from the broth by acidification to pH 2.0-2.5, treatment with active charcoal, and further extraction with butanol. Fradicin can also be removed directly from the broth by acidification to pH 2, filtration with the aid of supercel, and elution of the supercel with sodium hydroxide solution at pH 8. It is soluble in methanol, ethanol, butanols, and amyl alcohols; it is insoluble or only very sparingly soluble in ether, carbon tetrachloride, benzene, a c e t o n e , petroleum ether, and water. It is stable at 100° C. for 30 min at pH 7.0 and at rm. temp, at pH 7.0. At pH 2.0, 10 min at 60° C. is sufficient to destroy the activity completely, while at rm. temp, the activity is gradually lost at acid reactions. The spectrum of fradicin is as follows: Inhibition Organism units/gm Staphylococcus aureus 0 Bacillus mycoides 0 Bacillus subtilis 0 Escherichia coli 0 Streptomyces griseus 0 Trichophyton mentagrophytes 300,000 Trichoderma 55 250,000 Aspergillus niger 13 400,000 Fusarium sp. 50,000 Pénicillium notatum 750,000 Ceratostomella ulmi 1,000,000 Candida albicans 250,000 One unit is the amount of material necessary to inhibit the growth of P. notatum in 1 ml. of nutrient agar as determined by the agar-streak method of Waksman and Reilly (1944). See Swart et al., 1950. Fragaria "Royal Sovereign," a higher plant, aqueous extracts of the garden hybrid of which are effective in vitro against Staphylococcus

Cross references are indicated by SMALL CAPITALS

[1241

FRAGARIA VESCA

aureus but not against Escherichia coli. See Osborn, 1943. Fragaria vesca, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Fragzria vesca v. sempeffloreiu, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Frasera carolinensb, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Frasera parryi, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Fraxlnns berlander ana, a higher plant, aqueous extracts of the commercial wood of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Bacillus anthracis. See Sanchez et al., 1948. F rax in us chinensls, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Fraxinns excelsior, a tree, extracts of the litter of which are ineffective in vitro against Staphylococcus aureus. See Melin and Wiken, 1946. Freesia hybrida, a higher plant, aqueous extracts of the root, leaf, and bulb of which are effective in vitro against the spores of Neurospora crassa and are ineffective against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. frequence a d d , an antibiotic isolated from Penicillium frequentans and P. vesiculosum. It is weakly effective in vitro against Staphylococcus aureus and Salmonella enteritidis, and is ineffective against Escherichia coli, pneumococcus, Corynebacterium diphtheriae, and Streptococcus hemolyticus. Frequence acid crystals are dark yellow and melt at 155° C. The acid is very soluble in ethanol, slightly soluble in chloroform or water, insoluble in benzene or hexane, and very soluble in aqueous sodium carbonate. It is stable to acid and to alkali at 100° C. and is phenolic in character. The empirical formula is C5H5O3. TOXICITY. — Forty-five mg of the sodium salt given i.p. is tolerated by a 20 gm mouse; 24 mg i.v. and 30 mg orally produce no symptoms. Some of the drug is excreted in the urine but most is destroyed or otherwise disappears in the body. There is evidence of damage to the kidneys. It is reported to be without effect on leucocytes at 1:2,000; at 1:5,000 some leucocytes are still alive after 31/2 hr. See Spray and Robertson, 1947, unpublished; Pollock, 1947, unpublished. See also P E N I C I L L I U M FREQUENTANS; P E N I C I L L I U M CULOSUM.

VESI-

Freylinia cestroldes, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Frtedlander's bacillus, as test organism in vitro, see

POLYMYXINS.

Fritillaria imperlalls, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Fritillaria meleagris, a higher plant, aqueous extracts of the bulb of which are ineffective in vitro against Staphylococcus aureus and Esch-

erichia coll [1]. Other aqueous extracts of this plant are also ineffective against these two microorganisms [2]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. FroeUchia gracilis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. fnictigenin, an antibacterial substance obtained from the mold Fusarium fructigenum, having the empirical formula Ca-,Hn-«OiN2. Its m.p. is 129" C. Fructigenin is a colorless, neutral, optically active compound stable to mineral acids and to heat and destroyed by alkali. It is sparingly soluble in water and very soluble in organic solvents. The following microorganisms are inhibited in vitro by this s u b s t a n c e : Bacillus subtilis, Mycobacterium phlei, Staphylococcus aureus, and Streptococcus pyogenes. See Cook et al., 1947. Fuchsia fuigens, a higher plant, aqueous extracts of the garden hybrid of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osbom, 1943. Fuchsia hybrida, a higher plant, aqueous extracts of the flower and leaf of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus and the spores of Neurospora crassa [1], Other aqueous extracts of this plant inhibit Staph, aureus but not E. coli [2], See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Fuchsia magellanica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Fuchsia regia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Fuchsia serratifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Fumago saliclna, as test organism in vitro, see PEZIZA

SCLEROTIORUM.

Fumaria officinalis, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and in vivo against experimental malaria [2]. See [1] Osborn, 1943; [2] Spencer et al., 1947. fumigacin, a crystalline antibiotic isolated from culture filtrates of the molds Aspergillus fumigatus [1] and A. fumigatus mut. helvola [2]. It is also known as helvolic acid [2], It is extracted by treating the filtrate with charcoal, adjusting to pH 4, eluting with acetone, distilling, and dissolving in chloroform. Purification is a c c o m p l i s h e d by chromatographic absorption and recrystallization from aqueous acetone [2]. Another method reported [3] is extraction by adsorption on norit, elution with chloroform, and treatment with ether, followed by recrystallization from hot alcohol; this product, however, is probably contaminated with gliotoxin, another antibiotic produced by A. fumigatus [4]. The fine white needles [1, 2, 3] have a m.p. variously reported to be 185°187° [3], 212° [2], and 215°-220° C. [5], The proposed empirical formula is C.isHnOs. Fumigacin is levorotatory. It is sparingly soluble in water, moderately soluble in ether and benzene, and readily soluble in acetone, warm alcohol, chloroform, glacial acetic acid, and pyridine. The sodium salt is fairly soluble in water, but the calcium, magnesium, barium.

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[125] iron, copper, zinc, and mercury salts are very sparingly soluble in water. The activity of fumigacin is unaffected by boiling for 15 min at p H 10 or in 2 N acid; it is destroyed by boiling in N alkali for 15 min and by incubating with N alkali at 37° C. for 5 hr. The copper and zinc salts are unaffected by incubation with solutions of copper and zinc sulphate. The activity of the sodium salt is only slightly affected, if at all, by serum, pus, yeast extract, bacterial extract, liver extract, paraaminobenzoic acid, or whole blood [2], SPECTRUM.—Shigella flexneri, Shig. shigae, and Shig. sonnei are not affected in vitro by the sodium salt. The following microorganisms are inhibited [2]: Bacillus anthracis Clostridium oedematiens Clostridium septicum Clostridium welchii Corynebacterium diphtheriae gravis Escherichia coli Mycobacterium smegma Neisseria meningitidis Proteus Pseudomonas aeruginosa Salmonella enteritidis Salmonella typhi Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes Streptococcus viridans The following microorganisms are inhibited by fumigacin: Inhibitory concentration Organism inmg/cc Bacillus anthracis .006 [4] Bacillus mycoides .004 [6] Bacillus subtilis .016 [6], .156 [4] Escherichia coli more than 1.0 [6] Klebsiella pneumoniae .004 [6] Micrococcus tetragenus .06 [4] Mycobacterium phlei more than .032 [6] Mycobacterium smegma more than .032 [6] Staphylococcus albus .004-.006 [4] Staphylococcus aureus .001 [5], .014-.015 [4] Staphylococcus citreus .004 [4] Streptococcus sp. .156 [4] Streptococcus hemolyticus .005-.025 [4] Streptococcus viridans .312 [4] Investigators who used the preparation probably contaminated with gliotoxin reported inhibition of Aerobacter aerogenes, E. coli, Salm, breslau, and Salm. schottmuelleri at l:less than 40,000; B. cereus, B. megatherium, B. mycoides, B. subtilis, and Staph, aureus, at 1:500,000-1:1,250,000; and Sarcina lutea, at 1:4,000,000 [3], The following results have been obtained in tests against various saprophytic and pathogenic fungi [7]: Fungus Units of activity/gm Aspergillus clavatus 3,000 Candida albicans 8,900 Cryptococcus neoformans 30,000 Dematium sp. 22.000 Fusarium sp. 22,000 Pencillium luteum-purpurogenum 8,900 Trichophyton mentagrophytes 8,900, 14,800 A 1:5,500 dilution of fumigacin fails to inhibit the following pathogenic fungi in vitro [8]:

FUMIGACIN Achorion gallinae Achorion gypseum Achorion quinckeanum Achorion violaceum Bodinea violáceo Endodermophyton indicum Endodermophyton tropicale Endomycopsis albicans Epidermophyton cruris Epidermophyton perneti Epidermophyton rubrum Grubyella schoenleinii Microsporum equinum Microsporum ferrugineunt Microsporum fulvum Microsporum japonicum Sabouraudites audouini Sabouraudites felineus Sabouraudites lanosus Trichophyton album Trichophyton asteroides Trichophyton cerebriforme Trichophyton equinum Trichophyton granulosum Trichophyton sabouraudii Trichophyton tonsurans

TOXICITY AND PHARMACOLOGY.— Intravenous or s.c. inj of 10 mg of the sodium salt into 20 gm mice results in death within an hr; 5 mg causes toxic symptoms, but the experimental animals recover [2]. By stomach tube, 20 mg doses have no effect on mice [2], The i.p. LDso of fumigacin for 20 gm mice is 400 mg/kg [4] and the maximum tolerated dosage is 800 m g / k g [5]. In chronic experiments, there is 50% mortality in 20 gm mice receiving seven 10 mg doses of the sodium salt over a period of 4 days. Mice receiving ten 2 mg doses p.o. in 5 days show (at autopsy) slight kidney damage and severe liver damage. Six daily i.p. injs of 4 mg each cause 66% mortality, with aseptic plastic peritonitis and necrosis of the liver [2], In rabbits, inj of 0.5 cc of a 1:1,000 solution of the sodium salt into the cisternal space causes no damage or irritation. After 18 hr activity can be detected in the cerebrospinal fluid. Similar inj of a 1:250 solution results in muscular spasm, weakness, fits, and ultimate recovery. Single intradermal injs. cause hyperemia and edema; repeated injs produce fibroblastic reactions but no necrosis [2], A 1% solution of the sodium salt kills leucocytes within an hour; 1:1,600 is without effect. The sodium salt is excreted in bile and urine after administration by a n y r o u t e in mice [2], EXPERIMENTAL CLINICAL RESULTS — Doses of 1-10 mg given one to ten times at 12 hr intervals, i.v., s.c., and p.o., fail to protect mice from infections due to Staph, aureus and Strep, pyogenes but do prolong life. The very few mice that survive the infection die later, probably as a result of liver damage [2]. In Strep, hemolyticus infections in mice one or two s.c. injs of 2-4 mg give 50% protection [4]. See [1] Waksman et al., 1942; [2] Chain, Florey, Jennings, and Williams, 1943; [3] Waksman et al., 1943; [4] Menzel et al., 1944; [5] Waksman, 1945; [6] Kavanaugh, 1947b; [7] Reilly et al., 1945; [8] Sanders, 1946.

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

FUMIGATES

[ 126]

a crystalline antibiotic isolated from Aspergillus fumigatus [1], The maroon-colored needles melt at 116"C. [2] and have the structural formula [1]: ^ CHs I

I OH 1

OCHs

See [1] Anslow and Raistrick, 1938a; [2] Waksman, 1945. fungickUn, an antifungal agent from a soil actinomycete, which is reported to be effective in vitro against a large number of nonpathogenic and pathogenic fungi, including Candida albicans, Cryptococcus neoformans, Histoplasma capsulatum, Blastomyces dermatiiidis, Coccidiodes immitis, Paracoccidiodes brasiliensis, Trichophyton rubrum (purpureum), and T. mentagrophytes (gypseum). Crude preparations of fungicidin, injected repeatedly in sublethal doses into mice infected with Cryptococcus neoformans, prolong the life of the animals beyond that of the untreated controls. See Hazen and Brown, 1950. Funkia subcordata, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Furcraea tu be rosa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Fusarium, as test organism in vitro, see ACHROMOBACTER

Sp.

Fusarium sp., a fungus which is effective in vitro against Deuterophoma tracheiphila. See Savastano and Fawcett, 1930. As test organism

in

vitro,

s e e PSEUDOMONAS

FLUORESCENS.

Fusarium spp., various unidentified fungi of the genus Fusarium, some of which are ineffective in vitro against Staphylococcus aureus, Salmonella typhi, and Endomycopsis albicans. The culture media of these fungi inhibit Staph, aureus but not Botrytis allii [1], Other unidentified fusaria are effective in vitro against Staph, aureus [2,3] and Mycobacterium phlei [2]. See [1] Brian and Hemming, 1947; [2] Cook et al., 1947; [3] Carpenter, 1945. See also LATERITIINS. As test organisms in vitro see ACTINOMYCIN; ANTIBIOTIC X G ; CHAETOMIN; CLAVACIN; FRADICIN: FUMIGACIN; GLIOTOXIN; LEPTOTAENIA DISSECTA; R H U S HIRTA; STREPTOMYCIN; STREPTOTHRICIN; VIRIDIN. F o r l i t e r a t u r e

see Arnstein et al., 1946a (Fusaria). Fusarium avenaceum, a fungus which gives doubtful results when tested in vitro against Staphylococcus aureus and Escherichia coli [1]. This fungus is also reported to be ineffective against Staph, aureus, Salmonella typhi, and Endomycopsis albicans, and its culture media to be ineffective against Staph, aureus and Botrytis allii [2], Yet other investigators report that the fungus [3] and its culture media [4] inhibit Staph, aureus and Mycobacterium phlei. See [1] Robbins et al., 1945; [2] Brian and Hemming, 1947; [3] Cook et al., 1947; [4] Arnstein et al., 1946a. See also AVENACEIN. AS test organism in vitro

see ASPERGIL-

LIC ACID; BERBERINE; BURDOCK; CHEIROLINE; CLAVACIN; GLIOTOXIN; HELVOLIC ACID; MYCOPHENOLIC ACID; PENICILLIC ACID; SPIRAEA; TYROTHRICIN.

Fusarium bostrycoldes, a fungus, the culture fluid of which strongly inhibits the growth of the tubercle bacillus, H-37, when tested in vitro. The inhibiting action was found to be related to pigment production by the mold. The pigments were extracted from the mold mycellium with hot alcohol and from the highly colored culture fluid with benzene. After freeing of the extracts from fat by adsorption on alumina, a crystalline pigment was obtained with antibiotic activity toward the tubercle bacillus similar to the activity of streptomycin. This pigment, which has indicator properties, melts at 238°-239°C. and is a naphthaquinone similar to, but not identical with JAVANICIN. See Cajori et al., 1950. Fusarium coeruleum, a fungus which is effective in vitro against Endomycopsis albicans [1] but not against Staphylococcus aureus [1,2,3], Escherichia coli [2], Pseudomonas aeruginosa [2], Salmonella typhi [1], and Mycobacterium phiei [3]. The culture media of this fungus inhibit Botrytis allii but not Staph, aureus [lj. It is also reported that the culture media have no antibacterial activity [4], See [1] Brian and Hemming, 1947; [2] Wilkins and Harris, 1942; [3] Cook et al., 1947; [4] Arnstein et al., 1946a. For further reference see Johns, 1947, unpublished. As test organism in vitro see GLUTINOSIN.

Fusarium culmorum, a fungus which is ineffective in vitro a g a i n s t Staphylococcus aureus [1, 2, 3], Endomycopsis albicans [2], Escherichia coli [1], Pseudomonas aeruginosa [1], Salmonella typhi [2], and Mycobacterium phlei [3]. The culture media of this fungus inhibit Myco, phlei [4] and are ineffective against Staph, aureus [2,4] and Botrytis allii [2], In other tests in vitro this fungus is reported effective against Ophiobolus graminis [5,6,7] and Fusarium culmorum [5], See [1] Wilkins and Harris, 1942; [2] Brian and Hemming, 1947; [3] Cook et al., 1947; [4] Arnstein et al., 1946a; [5] Brömmelhues, 1935; [6] Broadfoot, 1933a and b; [7] Sanford and Broadfoot, 1931. As test organism in vitro, see BACILLUS sp.; CHEIROLINE; CLAVACIN; GLIOTOXIN; HELVOLIC ACID; LEPTOTAENIA DISSECTA; M U C O R s p . ; M U SARIN; MYCOPHENOLIC ACID; PENICILLIC ACID; R H U S HIRTA; TRICHODERMA LIGNORUM; TYROTHRICIN.

Fusarium dianthil, a fungus which is effective in vitro against Staphylococcus aureus and Mycobacterium phlei [1]. The culture media of this fungus give variable results when tested for antibiotic activity [2], See [1] Cook et al., 1947; [2] Arnstein et al., 1946a. Fusarium fructigenum, a fungus which is reported to be ineffective in vitro against Staphylococcus aureus, Salmonella typhi, and Encomycopsis albicans. The culture media of this fungus are ineffective against Staph, aureus and Botrytis allii [1]. Other investigators report that this fungus inhibits Staph, aureus and Mycobacterium phlei [2] and that the culture media inhibit Myco, phiei but not Staph, aureus [3]. It is also the source of FRUCTIGENIN. See [1] Brian and Hemming, 1947; [2] Cook et al., 1947; [3] Arnstein et al., 1946a. Fusarium graminearam, as test organism in vitro, see BACILLUS TRICHOTHECIN.

VULGATUS;

GLUTINOSIN;

Fusarium javanicum, a fungus which is effective in vitro against Escherichia coli but not against Staphylococcus aureus and Pseudo-

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[ 7] monas aeruginosa [1], It is also reported to be effective in vitro against Staph, aureus [2], Mycobacterium phlei [2], Verticiliium alboatrium [3], V. dahliae [3], Trichoderma sp. [3], Phoma sp. [3], and Fusarium sp. [31. The culture filtrate from this fungus is ineffective against Aspergillus parasiticus, V. albo-atrium, V. dahliae, Trichoderma sp., and Phoma sp.; it is only partially inhibitory for Penicillium notatum, Fusarium javanicum, F. lateritium, and F. sambucinum [3]. It is also the source of the antibiotic JAVANICIN. See [1] Wilkins and Harris, 1942; [2] Cook et al., 1947; [3] Arnstein et al., 1946a. As test organism in vitro, see Arnstein et al., 1946a (Fusaria). Fusarium lateritium, a fungus which is effective in vitro against Staphylococcus aureus and Mycobacterium phlei. The culture media are effective in vitro against Staphylococcus aureus and Mycobacterium phlei. See Cook et al., 1947. See also LATERITIINS. As test organism in vitro, see MUSARIN. For literature see Arnstein et al., 1946a (Fusaria.) Fusarium linf, as test organism in vitro, see MUSARIN.

Fusarium iycoperaici, 1 See LYCOMARASMINE. 2 As test organism in vitro, see ASPERGILLUS FACTOR; FACTOR.

BACILLUS

VULGATUS;

RHIZOCTONIA

Fusarium moniliforme, as test organism in vitro, see M YCOSUBTILIN. Fusarium niveum, as test organism in vitro, see BACILLUS MESENTERICUS

VULGATUS.

Fusarium orthoceras v. enniatinum, a fungus, the mycelia of which contain the antibiotic ENNIATIN.

Fusarium oxysporum f. batatas, as test organi s m in

vitro,

s e e IPOMOEA BATATAS.

Fusarium oxysporum f. conglutinans, as test

o r g a n i s m in vitro, see LYCOPERSICUM PIMPINEL-

LIFOLIUM. For literature see Little and Grubaugh, 1946 (vegetables). Fusarium oxysporum cubense, a fungus which is ineffective in vitro against Staphylococcus aureus and Mycobacterium phlei [1]. The culture media of this fungus also have no antibiotic activity [2], See [1] Cook et al., 1947; [2] Arnstein et al., 1946a. As test organism in vitro,

see

MUSARIN.

Fusarium oxysporum f. lycopersicl, as test org a n i s m in vitro, PERSICUM

see IPOMOEA BATATAS; LYCO-

PIMPINELLIFOLIUM;

MUSA

SAPIEN-

TUM; QUERCETIN; SOLANINE. F o r l i t e r a t u r e see

Little and Grubaugh, 1946 (vegetables). Fusarium oxysporum f. melonis, as test organism in vitro, see Little and Grubaugh, 1946 (vegetables). Fusarium oxysporum f. niveum, as test organism in vitro, see Little and Grubaugh, 1946 (vegetables). Fusarium oxysporum f. pisi, as test organism in vitro,

s e e LYCOPERSICUM PIMPINELLIFOLIUM.

Fusarium sambucinum, a fungus which is effec-

Gaertneria capitata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gafikya tetragena, as test organism in vitro, see ACTINOMYCIN; ANTIBIOTIC 1 3 6 ; ANTISMEGMATIS FACTOR; BACITRACIN; CHLORAMPHENICOL; GRAM-

GAILLARDIA PULCHELLA

tive in vitro against Staphylococcus aureus and Mycobacterium phlei [1], The culture media inhibit Staph, aureus, Streptococcus pyogenes, and Myco, phlei and fail to inhibit Escherichia coli [2]. It is also the source of SAMBUCININ. See

[1] C o o k

et al.,

1947;

[2]

Arnstein et al., 1946a. As test organism in vitro, see Arnstein et al., 1946a (Fusaria). Fusarium scirpi v. accuminatnm, a fungus which produces an antibiotic substance inhibitory to Mycobacterium tuberculosis. The active material passes through fritted glass and Mandler filters but is partially inactivated by passage through a Seitz filter. Heating to 100°C. for 15 min does not destroy the activity. See Boissevain, 1946. Fusarium soianl f. pisi, as test organism in vitro,

s e e LUPULON AND HUMULON.

fuscin, a crystalline antibiotic which is produced by the fungus Oidiodendron fuscum. It is obtained by aerating the culture filtrate and extracting the resulting precipitate with boiling ethanol. The crystals are orange, diamondshaped plates, with a m.p. of 230°C. TTie probable empirical formula is Cis HIB OS. They are soluble in chloroform, acetone, hot ethanol, ethyl acetate, and acetic acid; moderately soluble in ether and benzene; slightly soluble in cold ethanol; and nearly insoluble in light petroleum and water. Another active crystalline substance, dihydrofuscin, occurs with fuscin in the filtrates. The colorless rhombic crystals melt at 206 °C. The probable formula is Cis His Os. Fuscin forms a stable crystalline compound, C17 H22 Os S, with thioglycollic acid; this compound has a spectrum similar to that of fuscin. SPECTRUM.—Salmonella enteritidis, Salm. schottmuelleri, Shigella flexneri, and Shig. sonnei are partially inhibited at 1:5,000. The following are completely inhibited in vitro by fuscin at dilutions of 1:5,000 and greater: Bacillus anthracis Bacillus subtilis Corynebacterium diphtheriae gravis Corynebacterium diphtheriae intermedius Corynebacterium diphtheriae mitis Escherichia coli Mycobacterium phlei Mycobacterium smegmatis Proteus vulgaris Salmonella typhi Salmonella typhimurium Shigella shigae Staphylococcus albus Staphylococcus aureus Staphylococcus citreus Streptococcus pyogenes Streptococcus viridans Vibrio cholerae See Michael and Marcus, 1948.

ICIDIN; K O J I C ACID; LUPULON AND HUMULON; PENATIN; SUBTILIN; SULFACTIN; TYROCIDINE.

Gaiilardia pulcheiia, a higher plant, aqueous and ether extracts of the flower but not of the leaf, stem, and root of which are effective in vitro against Staphylococcus aureus and Esch-

Cross references are indicated by

SMALL CAPITALS

G A L A C T I N I A BADIA

(1281

erichia coli. None of these extracts inhibits the spores of Neurospora crassa [1]. Other aqueous extracts of this plant are ineffective against Staph, aureus and E. coli [2], See [1] Schnell and Thayer, 1949; [2] Osbom, 1943. G a b c t k d a badia, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Galactinla saccosa, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Calandras elwesii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Galantbus nivalis, a higher plant, aqueous extracts of the leaf and bulb of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against the spores of Neurospora crassa [1], Other aqueous extracts of this plant are ineffective against Staph, aureus and E. coli [2], See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Galega orientalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Caleopsis dubia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Galeopsls tetrahlt, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Galera hypnorum, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Galera mnlophlla, a fungus, extracts of the sporophores of which are ineffective in vitro a g a i n s t Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Galera mycenopsis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Galera pllcatella, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Galera rubiginosa, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus inhibit Staph, aureus but not E. coli and Pseudomonas aeruginosa [2], See [1] Wilkins, 1947c; [2] Wilkins and Harris, 1944d. Galera teñera, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Wilkins, 1948; [2] Wilkins and Harris, 1944d. Galera tibicystis, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1,2], See [1] Wilkins, 1948; [2] Hervey, 1947.

Galinsoga clliata, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Galinsoga parviflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2], See [1] Osborn, 1943; [21 Hayes, 1947. Galipea riedeliana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Galinm aparine, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and in vivo against experimental malaria [2]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [3]. See [1] Osborn, 1943; [2] Spencer et al., 1947; [3] Hayes, 1947. GaMnm cruciatum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Galinm mollugo, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Galium verum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Galleria mellonella, an insect, the bee moth, the blood of which contains an antibiotic, INSECTICIN. The larvae contain an acetone-soluble substance which is bacteriostatic and bacteriolytic for Mycobacterium tuberculosis. See Olivier, 1947. Galphimla glauca, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Galtonia candicans, a higher plant, aqueous extracts of the flower and stem of which are effective in vitro against Escherichia coli. Only extracts of the stem inhibit Staphylococcus aureus, and neither extract inhibits the spores of Neurospora crassa. See Schnell and Thayer, 1949. gangrene, clinical, see BACITRACIN; PENICILLIN; STREPTOMYCIN.

Ganoderma, sp., a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. It is also reported to be ineffective against these two microorganisms [2], See [1] Robbins et al., 1945; [2] Wilkins, 1947b. Ganoderma applanatnm, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1,2]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus [3, 4], E. coli [3, 4], and Pseudomonas aeruginosa [4], See [1] Wilkins, 1946b; [2] Wilkins. 1948; [3] Mathieson, 1946; [4] Wilkins and Harris, 1944d. Ganoderma colossum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948.

C r o s s r e f e r e n c e s a r e i n d i c a t e d by SMALL CAPITALS

[129] Ganoderma lucidum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947b. Ganoderma mindoroi, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Ganoderma mirabile, a fungus which is weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1948. Ganoderma oregonense, a fungus, the culture medium of which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. OREGONENSIN is obtained f r o m this plant [2], See [1) Wilkins, 1947b; [2] Muir, 1947, unpublished. Ganoderma resinaceum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against these two microorganisms [2], See [1] Wilkins, 1947a; [2] Wilkins, 1946a. Ganoderma rlvulosum, a fungus which is weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1948. Ganoderma sessile, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Garcinia oblongifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Garcinia ovalifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gardenia florida, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gardenia suaveolens, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Gardenia thunbergli, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Garrya elllptica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Garrya fremontii, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Garrya goldmanii, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gasteraloe pethamensis, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Gasteria aclnacifolia, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Gasteria carinata, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Gasteria excelsa, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949.

GENITA A M E R I C A N A

Gasteria maculata, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Gasteria obscura, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Gasteria pkta, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Gasteria punctata, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. gastric factor, an antibiotic substance found in the gastric contents of mice, dogs, rats, and human beings. It is not derived f r o m salivary contamination of the contents of the stomach. The gastric factor is active in vitro against Bacillus anthracis, B. globigii, Salmonella enteritidis, and Salm. typhi. See Ames et al.. 1946. Gaultheria procumbens, a higher plant, aqueous extracts of the leaf but not of the fruit of which are effective in vitro against Staphylococcus aureus; neither extract inhibits Escherichia coli [1], Various other extracts of this plant are ineffective against Bacillus subtilis [2], E. coli [2, 3], Staph, aureus [3], and Mycobacterium tuberculosis [3]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [4], See [1] Schnell and Thayer, 1949; [2] Sanders et al., 1945; [3] Gottshall et al., 1949; [4] Hayes, 1947. Gaura biennis, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Gaura iindheimeri, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gaylussacia baccata, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Geaster fimbria tus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Geaster quadrifidus, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Geaster triplex, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Pseudomonas aeruginosa [1]. See f l ] Wilkins and Harris, 1944d; [2] Mathieson, 1946. Geissospermum veilosii, a higher plant, extracts of the wood of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Geitnopleshim cymosnm, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Genipa americana, a higher plant, extracts of which are effective in vitro against Staphylo-

Cross references are indicated by SMALL CAPITALS

GENISTA HISPANICA

[130]

coccus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Genista hispanica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Genista —n™»"«, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Genista ttnctorla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gentiana sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gentiana acaolis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gentiana acuta, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gentiana andrewsii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See O s b o m , 1943. Gentiana caiycosa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gentiana äff. campannliformls, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gentiana sp. "corpus huart,** a higher plant, extracts of which are effective in the treatment of experimental malaria. See Spencer et al., 1947. Gentiana aff. detonsa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gentiana btea, a higher plant, some extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Mycobacterium tuberculosis in vitro [1]. Other extracts are ineffective against Staph, aureus and E. coli [2], and yet others are ineffective in the treatment of experimental malaria [3]. See [1] Gottshall et al., 1949; [2] Osborn, 1943; [3] Spencer et al., 1947. Gentiana porphyria, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gentiana pazodechlana, a higher plant, aqueous extracts of the garden hybrid of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gentiana saponaria, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gentiana saxosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gentiana sceptnim, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gentiana septemfida, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gentiana septemfida v. cordifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943.

Gentiana sino-ornata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gentiana Stramine», a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gentiana thermalls, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gentiana verna, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gentiana walujewl, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gentiana wntaiensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. gentisyl alcohol, an antibiotic isolated f r o m Pemcillium patulum and found effective in vitro against Staphylococcus aureus. It melts at 100°C. It is very soluble in water, ethanol, and ether; slightly soluble in benzene and chloroform; and insoluble in light petroleum. The empirical formula is CiHxCh. Gentisyl alcohol is considered to be 2:5-dihydroxybenzyl alcohol. The s t r u c t u r a l formula is as follows: OH CH2OH

OH See Birkinshaw et al., 1943; Brack, 1947. geodin, a crystalline antibiotic isolated f r o m the culture fluid of the mold Aspergillus terreus. It is extracted by adsorbing on charcoal, eluting with methanol, and recrystallizing f r o m methanol or aqueous acetone [1]. The m.p. is 227°-230°C. and the empirical formula is C17H12O7CI2 [2]. The structural formula is thought to be [2]:

h

X

t - O O-CHs

l - . , „ V T O OCH3 H

or O //

a

CH30 i V - - J \ / I a c 11 \ I \ o O ^ O OCHs H The following organisms are inhibited in vitro by concentrations of 1:1,000-1:128,000: Bacillus anthracis, B. subtilis, Corynebacterium

Cross references are indicated by SMALL CAPITALS

[131] diphtheriae gravis, Coryne. diphtheriae intermedins, Coryne. diphtheriae mitis, Mycobacterium sp., Myco, smegmatis, Shigella shigae, Staphylococcus albus, Staph, aureus. Staph, citreus, Streptococcus pyogenes, and Vibrio cholerae [2]. Escherichia coli and Pseudomonas fluorescens are inhibited by dilutions greater than 1:20,000 [1], The following are unaffected by 1:1,000: E. coli, Myco, phlei, Proteus vulgaris. Salmonella enteritidis, Salm. paratyphi, Salm. typhimurium, Shig jlexneri, and Shig. sonnei [2]. See [1] Rinderknecht et al., 1947; [2] Calam et al., 1947. Geoglossum glutinosum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Geoglossum opbioglossoides, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Geotricbum spp., as test organisms in vitro, see ACTIDIONE; ANTIBIOTIC

136.

Geranium, a higher plant, aqueous and ether extracts of the leaf of which are ineffective in vitro against Staphylococcus aureus, EscherNeurospora ichia coli, and the spores of crassa. See Schnell and Thayer, 1949. Geranium armenum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Geranium "Buxton's blue," a higher plant, aqueous extracts of the garden hybrid of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Geranhim dissectum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Geranium endressii, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Geranhim ibericum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Geranium iancastriense, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Geranium maculatum, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [2]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [3]. See [11 Osborn, 1943; [2] Gottshall et al.. 1949; [3] Hayes, 1947. Geranium molie, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Geranium napuligerum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Geranium niveum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

GEUM URBANUM

Geranium pretense, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Geranium robertianum, a higher plant, some extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and other extracts of which are slightly effective in the treatment of experimental malaria [2], See [1] Osborn, 1943; [2] Spencer et al., 1947. Geranium sanguineum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Geranium sanguineum v. album, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Geranium sibiricum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Geranium syivaticum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Geranium versicolor, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gerbera jamesonii, a higher plant, aqueous extracts of the seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Geum borisli, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Geum chiloense, a higher plant, aqueous extracts of the seed of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. Aqueous and ether extracts of the leaf, stem, and root are ineffective against Staph, aureus, E. coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Geum coccineum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Geum intermedium, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Geum "Mrs. Bradshaw," a higher plant, aqueous extracts of the garden hybrid of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Geum quellyoo, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Geum reptans, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Geum rivale, a higher plant, some extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and other extracts of which are ineffective in vivo against experimental malaria [2]. See [1] Osborn, 1943; [2] Spencer et al., 1947. Geum urbanuai, a higher plant, aqueous extracts of which are ineffective in vitro against

C r o s s references are indicated by SMALL CAPITALS

G E U M

V E R N U M

[132]

Staphylococcus aureus and Escherichia coli. See Osborn, 1943. G e r n Vernum, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus. Escherichia coli, Erwinia caroiovora, aad Phytomonas tumefaciens. See Hayes, 1947. Giardia enterka, as test organism in vitro, see ASPERGILLUS

NIGER.

Cibberclla saoblnetti, a fungus which gives doubtful results when tested in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1943. GH>berelU zeae, a fungus which gives doubtful results when tested in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. gigantic «cid, an antibiotic substance extracted from the mold Aspergillus giganteus. It is similar in chemical and biological properties t o penicillin. See Philpot, 1943. G Ilia capitata, a higher plant, aqueous extracts of the flower of which are effective in vitro against Escherichia coli and the spores of Neurospora crassa and are ineffective against Staphylococcus aureus. Aqueous extracts of the leaf, stem, root, and seedling are ineffective against these three organisms. See Schnell and Thayer, 1949. G ilia rosea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. GDIbertia arborea, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. GiUenla stipnlata, a higher plant, aqueous extracts of which show Dttle or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia caroiovora, and Phytomonas tumefaciens. See Hayes, 1947. Ginkgo biloba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. In another series of tests aqueous extracts are reported to show little or no inhibition of growth when tested in vitro against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2]. See (1] Osborn, 1943; [2] Hayes, 1947. giadioiic acid, a crystalline antibiotic isolated from the culture medium of the fungus Pénicillium gladioli. The active substance is extracted from the acidified culture filtrate by adsorbing on charcoal, eluting with ether, evaporating, and recrystallizing from water. The crystals are long, colorless, optically inactive needles, with a m.p. of 160°C. Giadioiic acid is a monobasic acid with the probable formula CnHioOs. Aqueous solutions retain their activity for at least 10 days at 25°C. and pH 3-8. Staphylococcus aureus is inhibited at pH 7 by 250 micrograms/cc; Escherichia coli and Salmonella typhi are unaffected by 500 micrograms/cc. At pH 3.5, 2 micrograms/cc prevents germination of the conidia of Botrytis allii; at pH 7, 100 micrograms/cc is required for the same effect. See Brian, Curtis, Grove, Hemming, and McGowan, 1946. Gladiolus communis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Gladiolus hybrid, a higher plant, aqueous extracts of the flower and ether extracts of the leaf of which are effective in vitro against Staphylococcus aureus while ether extracts of the flower, aqueous extracts of the leaf, and both aqueous and ether extracts of the stem are ineffective. Only ether extracts of the flower and aqueous extracts of the leaf inhibit Escherichia coli, and only aqueous and ether extracts of the flower inhibit the spores of Neurospora crassa. See Schnell and TTiayer. 1949. glanders, clinical, see P E N I C I L L I N . Glaucium, a higher plant, aqueous and ether extracts of the leaf and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Glauchim flavum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Glauchim flavum v. tricolor, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Glaucoma spp., as test organisms in vitro, see ACTINOMYCIN.

Glaziova bauhinioldes, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Glechoma hederacea, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gieditschia sinensis, a higher plant, concentrated aqueous extracts of the Chinese drug prepared from the stem of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus. See Gaw and Wang, 1949. Gleosporhim fructigenum, a fungus which is ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1942. Gliocladium sp., a fungus which is ineffective in vitro against Staphylococcus aureus, Salmonella typhi, and Endomycopsis albicans. The culture media of this fungus inhibit Botrytis allii but not Staph, aureus. See Brian and Hemming, 1947. Gliocladhim spp., as test organisms in vitro, see

BACILLUS

sp.

Gliocladhjm catenulatum, a fungus which is effective in vitro against Staphylococcus aureus but not against Salmonella typhi and Endomycopsis albicans. The culture media of this fungus inhibit Botrytis allii but not Staph, aureus. See Brian and Hemming, 1947. Gliocladium fimbriatum, a fungus which is ineffective in vitro against Staphylococcus aureus, Salmonella typhi, and Endomycopsis albicans. The culture media of this fungus inhibit Botrytis allii but not Staph, aureus. See Brian and Hemming, 1947. See also G L I O T O X I N . Gliocladium roseum, a fungus which is ineffective in vitro against Staphylococcus aureus, Salmonella typhi, and Endomycopsis albicans. The culture media of this fungus are ineffective against Staph, aureus and Botrytis allii. See Brian and Hemming, 1947. Gliomastix convoluta, as test organism in vitro, see

5-METHOXY-P-TOLUQUINONE.

gliotoxin, a crystalline antibiotic isolated from the culture filtrates of Aspergillus fumigatus

Cross references are indicated by

SMALL CAPITALS

[133] [1] and Gliocladium fimbriatum and/or Trichoderma viride [2, 3]. Gliotoxin occurs as elongated plates with a m.p. of 195°C. [4]. The structural formula has been shown to be [5]:

N —CHs

> — CH 2 It is stable in neutral and acid solution and very unstable in alkali [2], It is slightly soluble in water (70 mg/1) and soluble in acetic acid, acetone, acetonitrile, benzene, tert.-butanol, carbon tetrachloride, chloroform, dioxane, dimethyl formamide, ethyl acetate, ethanol, ethyl bromide, hydrochloric acid, methanol, and pyridine [6]. Gliotoxin is optically active and its ultraviolet absorption spectrum is similar to those of indole and tryptophan [6], Cysteine destroys the antibiotic activity of this agent [7]. SPECTRUM—Gliotoxin has the following antibiotic spectrum: Micrograms/cc required for inhibition Organism Aerobacter aerogenes 4.8 [6] 1,000.0 (doubtful Aspergillus niger results) [6] 100.0 [6] Bacillus mesentericus 0.25 [8] Bacillus mycoides 0.25 [8] Bacillus subtilis 500.0 [6] Blastomycoides dermatitidis 3.9-15.6 [6] Epidermophyton 10.0-12.7 [6], 25.0 [8] Escherichia coli 250.0 [6] Fames annosus 3.9 [6], 6.0 [8] Klebsiella pneumoniae 1,000.0 (doubtful Lactobacillus casei results) [6] 4.0 [8] Mycobacterium phlei 4.0 [8] Mycobacterium smegma 100.0 [6] Mycobacterium synxanthum 0.2 [6] Neisseria catarrhalis 2.5 [6] Neisseria pertussis 125.0 (doubtful Pénicillium digitatum results) [6] 1,000.0 [6] Pénicillium italicum 0.25 [8] Photobacterium fischeri 10.0 [6] Phytomonas michiganensis 0.234-0.312 [6] Pneumococci 500.0 [8] Pseudomonas aeruginosa 10.0 [6] Pseudomonas fluorescens 100.0 [6] Rhizopus Salmonella Salmonella Salmonella

enteritidis paratyphi schottmuelleri

Salmonella typhi Sarcina lutea Staphylococcus albus Staphylococcus aureus Streptococcus Streptococcus Streptococcus Trichoderma

lactis pyogenes viridans

3.9 [6] 5.0 [6] 10.0 (partial inhibition) [6] 5.0 [6] 10.0 [6] 2.5 [6] 0.234-1.0 [6], 0.15 [8] 1,000.0 [6] 0.937 [6] 1.0 [6] 250.0 (doubtful results) [6]

GLIOTOXIN

Some investigators report the activity of gliotoxin in units/gm [9], as follows: Organism Units/gm Aspergillus clavatus 200,000 Bacillus subtilis 2,000,000 Dematium sp. 6,000,000 Escherichia coli 15,000 Fusarium sp. 600,000 Pénicillium luteum-purpurogenum 600,000 In dilutions of 1:140,000 gliotoxin causes complete inhibition of Achorion gallinae, Epidermophyton cruris, G ruby ella schoenleinii, Microsporum ferrugineum, and Trichophyton album and partial inhibition of the following [10]: Achorion quinckeanum Endodermophyton tropicale Epidermophyton perneti Microsporum equinum Microsporum fulvum Sabouraudites audouini Sabouraudites lanosus Trichophyton asteroides Trichophyton cerebrijorme Trichophyton equinum Trichophyton granulosum The same concentration is ineffective against the following [10]: Achorion gypseum Achorion violaceum Bodinea violáceo Endodermophyton indicum Endomycopsis albicans Epidermophyton rubrum Microsporum japonicum Sabouraudites felineus Trichophyton sabouraudii Trichophyton tonsurans Gliotoxin completely inhibits the growth in vitro of the following organisms in the concentrations shown [12]: Organism Concentration Actinomyces scabies 1:448,000 Bacillus polymyxa 1:224,000 Bacillus subtilis 1:1,792,000 Bacterium aroidae 1:56,000 Claviceps purpurea 1:70,000 Corynebacterium sepedonicum 1:1,792,000 Leuconostoc sp. 1:448,000 Phytophthora erythroseptica 1:70,000 Sclerotinia sclerotiorum 1:70,000 Stereum purpureum 1:70,000 Xanthomonas begoniae 1:112,000 It is ineffective in vitro against Corynebacterium michiganense. Bacterium tumefaciens, B. carotovorum, Pseudomonas marginalis, Ps. syringae, X. campestris, X. malvacearum. The following are partially inhibited in vitro at concentrations of 1:70,000: Botrytis cinerea, Fusarium avenaceum, F. culmorum, Gloeosporium musarum. Pénicillium expansum, Pythium ultimum, Rhizoctonia crocorum, Rh. solani, Verticillium dahliae [12]. Filtrates from A. fumigatus presumably containing gliotoxin as the active principle fail to inhibit Treponema pallidum, Plasmodium lophurae, Trypanosoma lewisi, staphylococci, streptococci, pneumococci, meningococci, and Escherichia coli [11]. Filtrates from Gliocladium fimbriatum inhibit the spores of Sclerotinia americana and the hyphae of Rh. solani [2].

Cross references are indicated by SMALL CAPITALS

CLOBBA VARIABILIS

1134]

TOXICITY.—In rabbits i.v. inj of 45 mg/kg causes death in 1 hr, preceded by diarrhea and low blood pressure. The lethal i.p. and p.o. dose is 50 mg/kg for mice and 50-65 mg/kg for rats. In mice 25 mg/kg by either route results in only 50% mortality [6], Culture filtrates from A. fumigatus, apparently containing gliotoxin as the active agent, nave no effect on human sperm, rabbit tracheal cilia, or sheep erythrocytes. Although effective in vivo at 1:10-1:80 against cells of experimental lymphosarcoma, sarcoma, and carcinoma, these filtrates have no beneficial effect, even in nearly fatal doses, on the development of tumors in vivo in mice [11]. See [1] Menzel et al., 1944; [2] Weindling, 1941; [3] Brian, 1944; [4] Waksman, 1945; [5] Elvidge and Spring, 1949; [6] Johnson et al., 1943; [7] Cavallito and Bailey, 1944a; [8] Kavanaugh, 1947b; [9] ReUly et al-, 1945; [10] Sanders, 1946; [11] Kidd, 1947; [12] Gilliver, 1946. Globba variabilis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Globba wintttii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Globularia cordifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Gloeosporium spp., as test organisms in vitro, s e e BACILLUS s p .

Gloeosporium affine, as test organism in vitro, s e e A C T I N O M Y C E S ALBUS; SERRATIA MARCESCENS.

BACILLUS

SUBTILIS;

Gloeosporinm musarum, as test organism in vitro, s e e A C T I N O M Y C E S ALBUS; ASPERGILLIC ACID; BACILLUS SUBTILIS; BERBERINE; CHEIROLINE; CLAVACIN; G L I O T O X I N ; MYCOPHENOLIC ACID; PENICILLIC ACID; PROACTINOMYCIN; SERRATIA MARCESCENS; SPIRAEA; TYROTHRICIN.

Glomerella cingolata, as test organism in vitro s e e A C T I N O M Y C E S ALBUS; A C T I N O M Y C E S ANNULATUS; A C T I N O M Y C E S FLAVOVIRENS; ACTINOMYCES GOUGEROTI; A C T I N O M Y C E S HALSTEDII; A C T I N O M Y C E S MADURAE; A C T I N O M Y C E S VIRIDOCHROMOGENUS; BACILLUS CAROTOVORUS; BACILLUS MEGATHERIUM; BACILLUS MESENTERICUS VULGATIS; BACILLUS MYCOIDES; BACILLUS SUBTILIS; PSEUDOMONAS CAMPESTRIS; SARCINA sp.; SERRATIA MARCESCENS; STREPTOCOCCUS

LACTIS. For literature see Alexopoulos and Herrick, 1942 (actinomycetes). Gloriosa superba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gloxtalia, a higher plant, aqueous extracts of the garden hybrid of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. glutinosin, a crystalline fungistatic substance extracted from the culture filtrates of the mold Metarrhizium glutinosum. After extraction with ether, normal butanol, or petroleum ether, the supernatant is evaporated and the thin, colorless, plate-like crystals of glutinosin are recrystallized from ethanol. The m.p. is above 300°C. The empirical formula appears to be CisHeoOis.

Glutinosin is ineffective in vitro at 100 micrograms/cc against Escherichia coli. Salmonella typhi, and Staphylococcus aureus. Concentrations at or below 50 micrograms/cc at pH 3.5 prevent the germination of spores of Botrytis allii, Fusarium coeruleum, and Penicillium expansum, but not F. graminearum. An a s s o c i a t e d substance, with irritating properties similar to those of poison ivy, is extracted from the culture filtrates with glutinosin but remains in the mother liquor after the crystallization of glutinosin. See Brian and McGowan, 1946. Glyceria maxima, a grass, extracts of the litter of which are ineffective in vitro against Staphylococcus aureus. See Melin and Wiken, 1946. Glycosmis pentaphylla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gnaphalhim sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gnaphalhim cbeiranthifolhim, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gnetum gnemon, a higher plant, aqueous extracts of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus. See Osborn, 1943. Godetia grandiflora, a higher plant, extracts of the seed and seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Goethea strlctiflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gomphia decorans, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gomphia ollviformls, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gomphldium maculatus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Gomphidium roseus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Gomphidium viscidus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Gomphrena globosa, a higher plant, aqueous extracts of the flower, leaf, stem, root, and seedling, and ether extracts of the flower, leaf, and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Gonioma kamassi, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. gonococcal endotoxin, effect of, in mice, see PENICILLIN.

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[135] gonococcL 1 As test organisms in vitro,

see

GRAMICIDIN; INSECTICIN; TYRociDiNE. 2 E x p e r i mental

infections,

see

CILLIN. 3 T r e a t m e n t

ASPERGII.LIC ACID;

of clinical

PENI-

infections

caused b y , s e e AUREOMYCIN; CHLORAMPHENICOL; P E N I C I L L I N ; S T R E P T O M Y C I N ; T E R R A M Y C I N .

Gonolobus fulvidus, a higher plant, aqueous extracts of which are ineffective in vino against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. g o n o r r h e a , c l i n i c a l , see AUREOMYCIN; CHLORAMPHENICOL;

PENICILLIN; RHEIN;

TERRAMYCIN.

gonorrheal urethritis, clinical, see AUREOMYCIN; CHLORAMPHENICOL;

TERRAMYCIN.

Goodenia ovata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gordonia axillaris, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Gordonia dalgleishiana, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Gossypium herbaceum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. gramicidin, one of two antibiotic, crystalline, polypeptide components of tyrothricin [1]. It may be separated lrom tyrocidine, the other component, by virtue of the fact that it is soluble in an alcohol-ether mixture, while tyrocidine is not [1]. Separation of the two components is also effected by extracting tyrothricin with warm absolute acetone to dissolve the gramicidin [2]. It is purified by precipitating f r o m the acetone solution with ether, evaporating, and recrystallizing from warm absolute acetone [2]. The crystals appear as tiny platelets with pointed or rectangular ends, which have a m.p. of 228°-231"C. They are soluble in lower alcohols, acetic acid, acetone, and dioxane, and almost insoluble in water, ether, hydrocarbons, and chlorinated hydrocarbons [3]. The mol. wt. is 1,054 or 1,413 [4], A large proportion of the a-amino acids in the molecule have the d-configuration. It contains 1-tryptophane, d-leucine, and alanine [5]. It is hydrolyzed by acid; but it is completely resistant to the action of pepsin, trypsin, and papain [5] and is only slightly inhibited by serum, tissue extracts, and peptone [4], Gramicidin is principally bacteriostatic in action, but large c o n c e n t r a t i o n s are bactericidal [2], Gramicidin, while less hemolytic than tyrocidine, exhibits a "definite hemolytic effect" [6], 0.05 ppm being required to cause 50c£ hemolysis of rat erythrocytes in 40 min at rm. temp. [7]. It also depresses the surface tension of aqueous solutions [8]. Heat destroys the antibacterial and hemolytic activity of the agent but does not affect its property of lowering surface tension [8], Mixtures of gramicidin and penicillin exhibit a synergistic effect [9]. SPECTRUM.—The following organisms are inhibited in vitro by gramicidin: Bacillus anthracis [2] Clostridium spp. [2] Corynebacterium diphtheriae [10] Diphtheroid bacilli [10]

GRAMICIDIN S Diplococcus pneumoniae [2] Endameba histolytica [11] Gaffkya tetragena [2] Gonococci [10] Lactobacillus acidophilus [2] Meningococci [10] Mycobacterium leprae [2] Mycobacterium phlei [2] Mycobacterium ranae [2] Mycobacterium tuberculosis [2] Staphylococcus aureus [2] Staphylococcus citreus [2] Streptococcus fecalis [2] Streptococcus hemolyticus [2] Streptococcus mastitidis [2] The following are not affected by gramicidin:

Ascaris suis [11] Bartonella bacilliformis [12] Escherichia coli [10] Leishmania tropica [12] Leptospira icterohemorrhagiae [12] Trypanosoma cruzi [12] Trypanosoma lewisi [12] TOXICITY.—Mice are killed by single i.p. injs of 0.3-0.6 mg [1,2, 10], The i.p. M T D i s l O m g / k g [13]. Single i.v. injs of 0.075 mg are fatal to 20 gm mice [2], The i.v. M T D is 1.2 m g / k g [13], and the i.v. LD50 is 1.5 m g / k g [11]. Large oral and s.c. doses are tolerated, the M T D for both routes being more than 1,000 m g / k g [13], In 150-200 gm rats 20 m g / k g i.p. is lethal [7], and in dogs, 3 m g / k g i.v. is fatal in 48-72 hr [10], EXPERIMENTAL CLINICAL RESULTS. —Intraperitoneal inj of 0.001-0.002 mg protects mice against 10,000 lethal doses of pneumococci or Strep, hemolyticus; i.v., s.c., and i.m. injs are ineffective [10]. In pneumococcal hypopyon ulcers in rabbits, only slight beneficial effects are noted after local treatment of the lesions with gramicidin [14], VETERINARY CLINICAL RESULTS.— Bovine mastitis responds to gramicidin treatment when the causative organism is Strep, agalactiae [15]. Of four cases due to Strep, uberis, the results were satisfactory in only one [15], CHEMICAL DERIVATIVES OF GRAMICIDIN.—A formaldehyde derivative of gramicidin having the same antibacterial activity as the free substance is considerably less toxic and less hemolytic than gramicidin [7], Tlie lethal dose of the formaldehyde product for 150-200 gm rats is more than 450 m g / k g , while 0.6 ppm is required to produce 50% hemolysis in rat erythrocytes in 40 min at rm. temp. [7], The i.v. LDoo for mice is 4.7 m g / k g [11], Other derivatives have an i.v. LD30 for mice as high as 30 m g / k g [16]. See [1] Hotchkiss and Dubos, 1940a; [2] Hoogerheide, 1944; [3] Hotchkiss and Dubos, 1941; [4] Dubos, 1941; [5] Hotchkiss, 1941; [6] Rammelkamp and Weinstein, 1941; [7] Lewis, Dimick, Feustel, Fevold, Alcott, and FraenkelConrat, 1945; [8] Heilman and Herrell, 1941; [9] Foley and Lee, 1948; [10] Dubos and Hotchkiss, 1941; [11] Anderson et al., 1946; [12] Weinman, 1943; [13] Waksman, 1945; [14] Robson and Scott, 1943; [15] Little et al., 1940b; [16] Schales and Mann, 1948. See also TYROTHRICIN.

gramicidin S, an antibiotic derived from a Russian strain of Bacillus brevis [1], It is a crys-

Cross references are indicated by SMALL CAPITALS

GRAMIDINIC ACID

[136]

talline polypeptide compound [2] which is extracted from the culture filtrate by acidifying to p H 4.7, drying, taking up the residue in alcohol, and passing through a Seitz filter. Purification is effected by diluting the alcohol extract with water, removing lipoids with ether, adsorbing other impurities on charcoal, and refrigerating for crystallization [3]. The m.p. is 267-270°C. [1, 3J. The antibiotic is soluble in chloroform [1], ethanol, and acetone [2] and insoluble in water, acids, and alkalis [2], The dry crystals are stable at 160°C. Gramicidin S also resists autoclaving for 30 min at 120°C. [3], SPECTRUM.—The following organisms are inhibited by 7-10 micrograms/cc. Staphylococcus aureus, streptococci, Diplococcus pneumoniae, Clostridium histolyticum, and CI. welchii. Vibrio cholerae is inhibited by 25 micrograms/cc [3]. Gramicidin S is also effective against Escherichia coli [1]. TOXICITY.—The i.p. LDso in rats is 17 mg/kg. Human leucocytes are not affected by 400-800 micrograms/cc [3]. EXPERIMENTAL CLINICAL RESULTS. —Gramicidin S is highly effective in the treatment of guinea pigs [3] and rats [1] infected with CI. welchii. CLINICAL RESULTS.—Local application of gramicidin S is of value in the treatment of the following conditions in human beings: Abscesses [1, 4] Bums [1, 4] Empyema [1, 4] Gunshot wounds [1] Impetigo, contagious [4] Osteomyelitis, acute and chronic [1, 4] Otitis [1] Peritonitis [4] See [1] Gause and Brazhnikova, 1944b; [2] Belozersky and Passhina, 1944; [3] Gause and Brazhnikova, 1944a; [4] Sergiev, 1944. gramldlnlc acid, see TYROCIDINE. gramlnlc acid, see TYROCIDINE. gram-negative bacillary subacute bacterial endo-

carditis, clinical, see AUREOMYCIN; PENICILLIN.

gram-positive bacteria, as test organisms in vitro, s e e ANACARDIC ACID.

Grandinia brinkmannll, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Grandinia farinacea, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Grandinia granulosa, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. granuloma inguinale, clinical, see AUREOMYCIN; CHLORAMPHENICOL; P E N I C I L L I N ; S T R E P T O M Y C I N ; TERRAMYCIN.

G ratio la aurea, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. G ratíola officinalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Grevillea bipinnatifida, a higher plant, extracts of which are effective in vitro against Staph-

ylococcus aureus but not against Salmonella typhi. See Atkinson and Rainsford, 1946. Grevillea daliaceana, a higher plant, extracts of which are effective in vitro against Staphylo• coccus aureus and Salmonella typhi. See Atkinson and Rainsford, 1946. Grevillea oleoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Grevillea robusta, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Greyia sutherlandii, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Griffinia hyacinthina, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Grindelia nana, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Grindelia squarrosa, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. grisein, an antibiotic produced by a strain of Streptomyces griseus [1]. It is extracted from the culture filtrate by adsorption on norit, elution with 95% ethanol, and precipitation with methanol and acetone. Crude grisein is soluble in water and in 95% ethanol and insoluble in absolute ethanol, ether, and acetone. It is stable to 100°C. for 10 min and is not affected by cysteine, sodium thioglycolate, hydrazine, hydroxylamine, or semicarbazide. Although the presence of iron in the culture medium of the producing strain of S. griseus facilitates the production of grisein, it decreases the action of the antibiotic. Sensitive organisms develop resistance to grisein rapidly but show no evidence of cross resistance to streptomycin and streptothricin. Mixtures of grisein and streptomycin exert a synergistic effect on organisms sensitive to both agents [2]. SPECTRUM.—The following organisms are inhibited in vitro by grisein; Units of activity/mg of a "potent Organism preparation" Aerobacter aerogenes less than 30 Bacillus cereus 1,000 Bacillus megatherium 1,000 Bacillus mycoides less than 30 Bacillus subtilis 300 Escherichia coli 1,800 Klebsiella pneumoniae less than 30 Micrococcus lysodeikticus 30,000 Mycobacterium phlei less than 30 Mycobacterium tuberculosis less than 30 Proteus vulgaris less than 30 Pseudomonas aeruginosa less than 100 Pseudomonas fluorescens less than 100 Salmonella pullorum 30,000 Sarcina lutea less than 30 Serratia marcescens less than 100 Shigella alkalescens 1,800 Shigella dysenteriae 18,000 Shigella paradvsenteriae 18,000 Staphylococcus aureus 3,000

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[137] TOXICITY.—Experimental animals tolerate 500,000 units kg [2], EXPERIMENTAL CLINICAL RESULTS. —Mice are protected from Salm. schottmuelleri and Staph, aureus infections by 800-1,600 units [2]. See [1] Reynolds et al., 1947; [2] Reynolds and Waksman, 1948. Grisellna luckla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. grlseofulvln, an antibiotic isolated from the culture media of the mold Penicillium griseofulvum [1). It is identical with "curling factor" obtained f r o m P. janczewskii [2], The m.p. is 2 2 0 ° C . The proposed structural formula is as follows [2]: CHj

CHJO

HAKEA MACROCARPA

Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Guarea trkhilioides, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Guazuma tomentosa, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli t j ] and in vivo against experimental malaria [2]. See [1] Osborn, 1943; [2] Spencer et al., 1947. Guazuma ulmifolia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Guepinia pezizaeformis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Guettarda verticUlata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gunnera sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. gunshot wounds, see GRAMICIDIN S. Gustavla speciosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. G y m n o a s c u s sp., see CLAVACIN.

Gynocardia odorata, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gynura bicolor, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gypsophila elegans, a higher plant, aqueous extracts of the root and flower but not of the seed, seedling, and leaf of which are effective in vitro against Escherichia coli. None of these extracts inhibits Staphylococcus aureus and the spores of Neurospora crassa. See Schnell and ' Thayer, 1949. Gypsophila paniculata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Gyroporus eyanescens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d.

C—O-CHs Griseofulvin causes stunting, excessive branching, and distortions in the germ tubes of Botrytis allii [2]. See [1] Oxford, Raistrick, and Simonart, 1939; [2] Grove and McGowan, 1947. Grosmannia serpens, a fungus which gives doubtful results when tested in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Grubyella schoenleinii, as test organism in vitro, s e e ASPERGILLIC ACID; CHEIROLINE; CLAVACIN; F U M I G A C I N ; GLIOTOXIN; MYCOPHENOLIC ACID; PEN1C1LLIC ACID; PROACTINOMYCIN.

Gualacum sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gualacum coulterl, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Gualacum officinale, a higher plant, aqueous extracts of which are ineffective in vitro against

H h a b bite, see CEPHERANTHIN.

Haberlea rhodopensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Habranthus texanus, a higher plant, extracts of the bulbs of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Haemanthus albiflos, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Haemanthus katharinae, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Haematoxylon campcchianum, a higher plant

(logwood), aqueous extracts of which are reported to be ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Haematoxylon cf. campechianum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. hair fat, free saturated aliphatic acids obtained from hair fat and containing 7-11 carbon atoms inhibit the growth of Microsporum audouini in concentrations of 0.0002-0.001%. See Rothman et al., 1945. Haematoxyk>D campechianum, a higher plant (logwood), aqueous extracts of which are. reported to be ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Cross references are indicated by SMALL CAPITALS

HALENIA DEFLEXA

[138]

Halenla deflcxa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Halleria hiclda, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbora, 1943. Halorrliagb micrantha, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbora, 1943. Hamamelis mollis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbora, 1943. Hamamelis vlrginiana, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Hamelia patens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hannoa klaineana, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Hannoa undulata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Hanseniaspora melligerl, as test organism in vitro, s e e ASPERGILLUS FACTOR; L U P U L O N H U M U L O N ; RHIZOCTONIA FACTOR.

AND

Hansenula anomala, a fungus, the culture media of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1943a. As test organism in vitro, see ACTIDIONE; ANTIBIOTIC 1 3 6 ; ASPERGILLUS FACTOR; L U P U L O N AND H U M U L O N ; MYCOSUBTILIN; RHIZOCTONIA FACTOR.

Hansenula apkulata, as test organism in vitro, see

ACTIDIONE.

see

ASPERGILLUS

Harpephyllum caffrum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Harrlsonia sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Harrlsonia abyssinica, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Hartmanella hyallna, as test organism in vitro, NIGER.

Hasseltia sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Haverhill fever, clinical, see PENICILLIN; STREPTOMYCIN.

heart. Extraction of sheep heart muscle with acetone followed by lyophilization yields a residue which inhibits chicken fibroblasts and mouse breast cell tumors in vitro. It is also inhibitory for Escherichia coli, Staphylococcus aureus, Mycobacterium tuberculosis, and Streptococcus hemolyticus. See Hoffman et al., 1948. Hebeloma sp., a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Hebeloma anthracophjlum, a fungus, extracts of the sporophores of which are effective in

vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hebeloma clavkeps, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hebeloma crustulinifonne, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hebeloma hiemale, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Hebeloma longicaudum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Hebeloma mesophaeum, a fungus, extracts of the sporophores of which are reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b) to inhibit Staph, aureus but not E. coli and Pseudomonas aeruginosa [2]. See [1] Mathieson, 1946; [2] Wilkins and Harris, 1944d. Hebeloma sacchariolens, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hebeloma strophosum, a fungus, extracts of the sporophores of which are effective in vitro against Staphyloccocus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hebeloma testaceum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hebeloma versipelle, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hebenstreltia tenuifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hedera helix, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the leaves are slightly effective in the treatment of experimental malaria. [2], In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [3], See [1] Osborn, 1943; [2J Spencer et al., 1947; [3] Hayes, 1947. Hedychium gardneriantim, a higher plant, aqueous extracts of the garden hybrid of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hedyosmum arborescens, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al, 1947. Hedysarum esculentum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Osborn, 1943.

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

HELMINTHOSPORIUM SATIVUM

[139] Heimia sallcifolia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Helenlum autumnale, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Helenium blgelovii, a higher plant, aqueous ext r a c t s of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Helenium tenuifolium, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Heliantbemum, a higher plant, aqueous extracts of the garden hybrid of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Heliantbemum chamaecistus, a higher plant, a q u e o u s extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Heliantbemum vulgare, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Helianthus annuus, a higher plant, aqueous and ether extracts of the seedling leaf of which are effective in vitro against Escherichia coli, while aqueous extracts of the seed, seedling, stem, root, flower, and leaf, and ether extracts of the flower and leaf are ineffective. Only ether extracts of the leaf inhibit Staphylococcus aureus and only aqueous extracts of the flower and leaf inhibit the spores of Neurospora crassa [1]. Other extracts of this plant inhibit Staph, aureus but not E. coli [2], Yet other extracts are reported to inhibit both Staph, aureus and E. coli [3]. See [1] Schnell and Thayer, 1949; [2] Carlson, Douglas, and Robertson, 1948; [3] Carlson and Douglas, 1948a. Helianthus decapetalus, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Helianthus giganteus, a higher plant, some extracts of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus [1,2] and other extracts of which are ineffective against Staph, aureus and E. coli [3]. See ¡1) Carlson, Douglas, and Robertson, 1948; [2] Carlson and Douglas, 1948a; [3] Osborn, 1943. Helianthus mlcrocephalus, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Helianthus mollis, a higher plant, extracts of which are effective in vitro against Bacillus subtilis but not against Escherichia coli. See Sanders et al., 1945. Helianthus trilineatum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Helianthus tuberosus, a higher plant, some extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Mycobacterium tuberculosis [1] and other extracts of which are ineffective against Staph, aureus [2], E. coli [2, 31, and Bacillus subtilis [31. See [1] Gottshall et al., 1949; [2] Osborn, 1943; [3] Sanders et al., 1945.

Heiichrysum bracteatum, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1,2], Escherichia coli [1.21, and Proteus X-19 [2]. See [1] O s b o r n , 1943; [2] C a r d o s o and Santos, 1948. Helichrysum parviflorum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et aJ., 1947. Helicobasidium purpureum, a fungus which is weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1948. Heliophylla leptophylla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Heliopsis heliantboides, a higher plant, various extracts of which are reported a) t o be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b ) to be effective against Bacillus subtilis and E. coli [2], See [1] Carlson, Douglas, and Robertson, 1948; [2] Sanders et al., 1945. Heliopsis laevis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Heliopsis scabra, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Helipterum humboldtianum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Helipterum roseum, a higher plant, aqueous extracts of the flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other aqueous extracts of this plant are also ineffective against Staph, aureus and E. coli [2], See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Helleborus corsicus, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Helleborus niger, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Helleborus viridis, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Helminthosporium, as test organism in vitro, s e e SCLEROTIUM

ROLFSII.

Helminthosporium avenae, a f u n g u s which is effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1942. Helminthosporium gramineum, as test organism in vitro,

s e e BACILLUS MESENTERICUS VULGATUS.

in vitro,

s e e BACILLUS MESENTERICUS VULGATUS.

CILLUS

MESENTERICUS,

Helminthosporium inaequalis, as test organism Helminthosporium sacchari, as test organism in vitro, see TRICHOTHECIN. Helminthosporium sativum, a f u n g u s which in vitro inhibits the growth of Ophiobolus graminis [1, 2] and Helminthosporium sativum [1], See [1] Brömmelhues, 1935; [2] Broadfoot, 1933a and b and Sanford and Broadfoot, 1931. As test organism in vitro see BACILLUS sp., BA-

Cross references are indicated by SMALL CAPrrALS

BACILLUS

VULGATUS;

[140]

HELMINTHS CEPHALOTHECIUM ROSEUM; TKICHODERMA LIGNORUM.

CHLORAMPHENICOL;

litlmhHn, worms, extracts from the tissues of which are reported to possess antibacterial activity. See Pavan, 1949. HetreDa crispa, a fungus, extracts of the spirophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Helvetia lacunosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. helvolic acid, obtained from Aspergillus fumigatus mut. helvola, completely inhibits the growth in vitro of the following organisms in the concentrations given: Organism Concentration Bacterium aroidae 1:5,000 Corynebacterium sepedonicum 1:160,000 Pseudomonas marginalis 1:20,000 Pseudomonas syringae 1:40,000 Xanthomonas campestris 1:40,000 Xanthomonas malvacearum 1:20,000 It is ineffective in vitro against Bacterium carotovorum, Botrytis cinerea, Fusarium avenaceum, F. culmorum, Penicillium expansum. See Gilliver, 1946. See also FUMIGACIN. Helxine solierolii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Hemerocallls fulva, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al„ 1945. Hemicliroa diandra, a higher plant, extracts of which are effective in vitro against Salmonella typhi but not against Staphylococcus aureus. See Atkinson and Rainsford, 1946. Hemophilus spp., as test organisms in vitro, see TYROCIDINE.

Hemophilus ducreyi, as test organism in see

vitro,

TYROTHRICIN.

Hemophilus hemolyticus, as test organism in vitro,

see AUREOMYCIN.

Hemophilus influenzae, as test organism in vitro, s e e ACTINOMYCIN; AUREOMYCIN; AYFIVIN; BACITRACIN; CHLORAMPHENICOL; LEPTOTAENIA DISSECTA; MICROCOCCIN; N E O M Y C I N ; POLYMYXI N S ; R H U S HIRTA; STREPTOMYCIN; STREPTOTHRIC I N ; TERRAMYCIN; TILLANDSIA USNEOIDES; TY' ROTHRICIN.

Hemophilus parainfluenzae, as test organism in vitro,

see

AYFIVIN;

TYROTHRICIN.

Hemophilus parapertussis, as test organism in vitro, s e e AUREOMYCIN; CHLORAMPHENICOL; P O L Y M Y X I N S ; STREPTOMYCIN.

Hemophilus pertussis, 1 As test organism in vitro, s e e ACTINOMYCIN; AUREOMYCIN; CHLORAMPHENICOL; MYCOSUBTILIN; N E O M Y C I N ; POLYM Y X I N S ; STREPTOMYCIN; TERRAMYCIN. 2 Ex-

perimental infections, see POLYMYXINS. Hemophilus suis, as test organism in vitro, see ACTINOMYCIN;

STREPTOTHRICIN.

Henoonia brhtonii, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Heracieum lanatum, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Cross references are in

Heracieum villosum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. HerMera macrophylla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hermandia cordlgera, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hermanodactylus tuberosus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. herpes zoster, clinical, see AUREOMYCIN; PENICILLIN;

STREPTOMYCIN.

Herpestis roonnieria, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. herquein, a yellowish-brown crystalline antibiotic isolated from the culture media of the fungus Penicillium herquei. It is obtained by acidifying the culture filtrate, suspending the resulting precipitate in water, and extracting with chloroform, followed by extraction into water at pH 7.5, precipitation with hydrochloric acid, and recrystallization from benzene or aqueous alcohol. The crystals melt at 129°C. (decomp.) and have the probable formula C19H20O8. The antibiotic is soluble in water, ethanol, chloroform, ether, carbon tetrachloride, and benzene, and insoluble in petroleum ether. The culture media of P. herquei inhibit the following in vitro: Mycobacterium phlei Pseudomonas aeruginosa Shigella shigae Staphylococcus albus Staphylococcus aureus Streptococcus pyogenes Vibrio cholerae Herquein inhibits Staph, aureus and V. cholerae at 1:2,500, and Corynebacterium xerosis and the El Tor vibrio at 1:500. See Burton, 1949. Hesperts matronalls, a higher plant, aqueous and ether extracts of the leaf and root of which are effective in vitro against the spores of Neurospora crassa. Aqueous extracts of the seed and seedling and aqueous and ether extracts of the leaf and root inhibit Staphylococcus aureus. None of these extracts inhibits Escherichia coli. See Schnell and Thayer, 1949. Heterocentron roseum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Osborn, 1943. Heterocentron subtriplinervum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Heterodendrum dlverstfollura, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Heteropteris chrvsophylla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Heteropteris nmbellata, a higher plant, aqueous extracts of which are ineffective in vitro against : a t e d b y SMALL CAPITALS

[141] Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Heterothalamus alienus, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Heuchera amerkana, a higher plant, various sxtracts of which are ineffective in vitro against Staphylococcus aureus [1], Escherichia coli [1, 2], and Bacillus subtilis [2]. See [1] Osborn, 1943; [2] Sanders et al., 1945. Heuchera brtzoldes, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Heuchera sangnlnea, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. In another series of tests in vitro, aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2]. See [1] Osborn, 1943; [2] Hayes, 1947. Heachera vlllosa, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Hevea brazilknsis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Heynia trijuga, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hibbertia dentata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hibbertia volubills, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hibiscus esculentus, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Hibiscus moscheutos, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Hibiscus oculiroseus, a higher plant, aqueous extracts of the flower of which are effective in vitro against Staphylococcus aureus while aqueous extracts of the stem, ether extracts of the flower and stem, and aqueous and ether extracts of the leaf are ineffective. Only aqueous extracts of the stem inhibit Escherichia coli. The spores of Neurospora crassa are not affected by ether extracts of the flower and stem, aqueous extracts of the stem, or aqueous and ether extracts of the leaf. See Schnell and Thayer, 1949. Hicoria pecan, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Hldalgoa wercklel, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

HIPPOCRATEA VOLUBILIS

Hierachim amplexicaule, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Hierachim aurantiacum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Hierachim florentinum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Hierachim gymnocephalum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Hierachim intybaceum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hierachim macula tum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hierachim muroram, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Hierachim pictum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Hierachim pUosella, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hierachim rupestre, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Hierachim umbeilatum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Hierachim venosum, a higher plant, aqueous extracts of the leaf and root of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2], See [1] Schnell and Thayer, 1949; [2] Hayes, 1947. Hippeastrum sp., a higher plant, extracts of the bulbs of which are effective in treating experimental malaria. See Spencer et al., 1947. Hippeastrum cf. flammigenun, a higher plant, extracts of the bulbs of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Hippeastrum punkeum, a higher plant, extracts of the bulbs of which are effective in the treatment of experimental malaria. See Spencer et al., 1947. Hippeastrum vittatum, a higher plant, extracts of the bulbs of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Hippocratea obtusifolia v. indka, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hippocratea volubills, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947.

Cross references are indicated by SMALL CAPITALS

m P P O C K E P I S COMOSA

[142]

Hlppocrcpis comosa, a higher plant, aqueous extracts of which are ineffective in vilro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hiptage madablota, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Hlrneola sp., a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1]. The culture medium inhibits Staph, aureus but not E. coli [2], See [1] Robbins et al., 1945; [2] Wilkins, 1947b. hirsutic acids, a group of one inactive acid precursor, two antibacterial acids, and four unidentified antibacterial substances obtained from the culture medium of the mold Slereum hirsutum. Hirsutic acid C is the inactive crystalline precursor with the formula C15H20O4 which is obtained by amyl acetate extraction of the culture fluid. The large rhombohedral crystals, which have a m.p. of 179.5°C., are optically active, sparingly soluble in water, and soluble in most organic solvents except hexane and carbon tetrachloride. Mice weighing 31 gm survive a single i.v. inj of 24 mg of hirsutic acid C. Noncrystalline hirsutic acid N occurs naturally in the culture fluid and may also be obtained by incubating acid C with the fungal mycelium or a mycelial extract. Extraction with ether and water isolates this acid from the amyl acetate extract of the culture fluid. It is a transparent, colorless, noncrystalline solid, slightly soluble in hot water and soluble in alkali and most organic solvents. The free acid, which has no sharp m.p., is indefinitely stable as the solid or in ether solution; it is less stable as the sodium salt in water solution. Hirsutic acid N inhibits in vitro the following microorganisms: Bacillus anthracis, B. subtilis, Corynebacterium diphtheriae, El Tor vibrio, Micrococcus lysodeikticus, Neisseria meningitidis, Sarcina lutea, Staphylococcus aureus, and Streptococcus pyogenes. It is ineffective against Aerobacter aerogenes, Chromobacterium prodigiosum, Escherichia coli, Klebsiella pneumoniae, Proteus, Pseudomonas aeruginosa, and Salmonella typhi. A crude preparation having one-eighth to one-fourth of the activity of the pure acid kills l e u c o c y t e s i m m e d i a t e l y at 1:4,000; 1:16,000 has no effect. Mice weighing 20-22 gm tolerate single i.v. doses of 1-2 mg; 6 mg doses are fatal within 5 min. Oral doses of 20 mg have no effect. Intravenous administration in cats causes a rise in b.p. but does not change respiration. Perfusion of the cat heart with a 1:25,000 dilution causes irreversible slowing, relaxation of tone, and dimunition of a m p l i t u d e . Acid N causes no specific changes in the motility of the isolated guineapig uterus. Hirsutic acid A, also noncrystalline, is obtained by treating acidified ether extracts of acid C with alkali. It is soluble in the agents that dissolve acid C. It is effective in vitro against Staph, aureus and Strep, pyogenes and ineffective against E. coli and Salm. enteritidis. Acid A is similar to acid C in its effect on leucocytes but is less toxic to 20-22 gm mice, 20 mg i.v. being required to cause death. No changes are observed in b.p and respiration of the cat after

i.v. inj. Perfusion of the rabbit heart with dilutions of 1:10,000 and 1:50,000 results in a slight, reversible decrease in amplitude, rate, and coronary flow. Of the four unidentified antibiotic agents obtainable from this fungus, two occur naturally; one results from the action of dry heat on acid C; and the fourth, from the action of acid on acid C. See Heatley et al., 1947. Histoplasma capsulatum, as test organism in vitro, s e e AUREOMYCIN; BACITRACIN; CHLORAMPHENICOL; LEPTOTAENIA DISSECTA; N E O M Y C I N ; PENICILLIN; PHTHIOCOL; PLUMBAGOL; POLYMYXINS; POLYPEPTIN; STREPTOMYCIN.

Hodgkin's disease, clinical, see AUREOMYCIN. Hoberia populnea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Holarrhena antidysenterica, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Holarrhena febrifuga, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Holcus mollis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Holmskioldia sanguinea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Homalomena caerulescens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hordeum vulgare, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hormodendrum spp., as test organisms in vitro, s e e CHLORAMPHENICOL;

EUMYCIN.

Hormodendrum compactum, as test organism in

vitro,

see

ACTIDIONE; ANTIBIOTIC

136.

Hormodendrum olivaceum, as test organism in vitro,

see ANTIBIOTIC X G .

Hormodendrum pedrosoi, as test organism in vitro, s e e ACTIDIONE; ANTIBIOTIC 1 3 6 ; MYCIN.

BACILLO-

horseradish, a garden vegetable, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, Phytomonas campestris, and Ph. phaseoli. See Lucas and Lewis, 1944. Hortia sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Hortia arborea, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Hosta caerulea, a higher plant, aqueous extracts of the leaf of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Hosta plantaginea, a higher plant, aqueous extracts of the leaf of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Hottonia palustris, a higher plant, aqueous extracts of which are ineffective in vilro against Staphylococcus aureus and Escherichia coli. See Ösborn, 1943. Houstonia caerulea, a higher plant, aqueous extracts of which show little or no inhibition of

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[143] growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Houstonia longifolia, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumejaciens. See Hayes, 1947. Hoya bella, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hoya carnosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. human bite, infected, clinical, see BACITRACIN. Humea elegans, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Humicola spp., as test organisms in vitro, see A C T I N O M Y C I N ; BACILLUS s p . h u m u l o n , s e e L U P U L O N AND H U M U L O N .

Humulus americanus, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Humulus lupulus, the hops plant, various extracts of which are reported a ) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and b ) to inhibit Staph, aureus [2, 3,4], E. coli [2, 3,4], and Mycobacterium tuberculosis [4], It is also the source of the

antibiotics

LUPULON

AND

HUMULON.

See

[1] Osborn, 1943; [2] Carlson, Douglas, and Robertson, 1948; [3] Carlson and Douglas, 1948a; [4] Gottshall et al., 1949. Hunnemania fumariaefolla, a higher plant, aqueous extracts of the seed and seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Hura crepitans, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hyacinthus azureus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hyacinthus orientalis, a higher plant, aqueous extracts of the flower, leaf, root, and bulb of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other aqueous extracts of this plant are also ineffective against Staph, aureus and E. coli [2]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Hyacinthus orientalis v. alba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hyacinthus romanus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hydnocarpus anthelminticus, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hydnocarpus ilicifolius, a higher plant, aqueous extracts of which are effective in vitro against

HYDNUM

REPANDUM

Staphvlococcus aureus and Escherichia coli. See Osborn, 1943. Hydnocarpus wightianus, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hydnum abietinum, a f u n g u s which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Hydnum abietis, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. The culture medium inhibits Staph, aureus but not E. coli [2], See [1] Hervey, 1947; [2] Wilkins, 1947b. Hydnum abietis (?), a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Hydnum auriscalphim, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Wilkins, 1948; [2] Wilkins and Harris, 1944d. Hydnum caput-ursi, a f u n g u s which is reported a) to be weakly inhibitory in vitro f o r Staphylococcus aureus a n d / o r Escherichia coli [1, 2] and b ) t o inhibit Staph, aureus and E. coli [3]. See [1] Wilkins, 1948; [2] Wilkins. 1947b; [3] Robbins et al., 1945. Hydnum chrysocomum, a f u n g u s which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Hydnum cirrhatum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hydnum coralloides, a f u n g u s which is reported a ) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b ) to be ineffective against these two microorganisms [2], See [1] Robbins et al., 1945; [2] Wilkins, 1946b. Hydnum erinaceum, a f u n g u s which is reported a ) t o be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b ) to be weakly inhibitory f o r Staph, aureus a n d / o r E. coli [2]. T h e culture media of this f u n g u s are weakly inhibitory f o r Staph, aureus a n d / o r E. coli [3]. See [1 R o b b i n s et al., 1945; [2] Wilkins, 1948; [3] Wilkins, 1947a. Hydnum imbricatum, a f u n g u s which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores of this fungus inhibit Staph, aureus but not E. coli and Pseudomonas aeruginosa [2], See [1] Wilkins, 1948; [2] Wilkins and Harris, 1944d. Hydnum nigrum, a fungus, extracts of t h e sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hydnum ochraceum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2]. See [1] Wilkins, 1948; [2] Robbins et al., 1945. Hydnum pulcherrimum, a f u n g u s which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], See [1] Wilkins, 1948; [2] Robbins et al., 1945. Hydnum repandum, a fungus, extracts of the sporophores of which are reported a ) to be

Cross references are indicated by SMALL CAPITALS

HYDNUM REPANDUM

[144]

effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to inhibit Staph, aureus and E. coli but not Pseudomonas aeruginosa [2], See [1] Mathieson, 1946; [2] Wilkins and Harris, 1944d. Hydnnm repandnm v. rafescens, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Wilkins, 1946a. Hydnum schnektermayeri, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1], It is also reported to be weakly inhibitory for Staph, aureus and/or E. coli [2], See [1] Robbins et al., 1945; [2] Wilkins, 1947b. Hydnnm septentrional«, a fungus which is reorted a) to be weakly inhibitory in vitro for taphylococcus aureus a n d / o r Escherichia coli [1, 21 and b) to inhibit Staph, aureus and E. coli [3], See [1] Wilkins, 1948; [2] Wilkins, 1947b; [3] Robbins et al., 1945. Hydnnm zooatnm, a fungus, extracts of the sporophores of which are reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and b) to inhibit Staph, aureus and E. coli but not Pseudomonas aeruginosa [2]. See [1] Mathieson, 1946; [2] Wilkins and Harris, 1944d. Hydrangea sp., a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Hydrangea aborescens, a higher plant, extracts of which are effective in vitro against Bacillus subtilis but not against Escherichia coli [1]. Extracts of the root of this plant are slightly effective in the treatment of experimental malaria [2], See [1] Sanders et al., 1945; [2] Spencer et al., 1947. Hydrangea macrophylla, a higher plant, aqueous extracts of the leaf of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Hydrangea petfolarls, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hydrangea sargentiana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hydrastis canadensis, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Mycobacterium tuberculosis but not against Escherichia coli. See Gottshall et al., 1949. Hydroclels commersonll, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

?

H y d r o c o t y l e asiatica, see CENTELLA ASIATICA.

Hydrophyllnm appendicnlatnm, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Hydrophyllnm capitaturn, a higher plant, the dwarf waterleaf, extracts of which are effective in vitro against Staphylococcus aureus. Two-week-old chicks injected with the extracts mixed with blood containing Plasmodium gallinaceum fail to develop malaria. In addition, the extracts are somewhat effective in the treatment of experimental malaria in

chicks but are without effect in Diplococcus pneumoniae infections in mice. Doses of 0.5 to 1.0 cc injected i.p., s.c, or i.v. in chicks and mice are lethal. Smaller amounts are anesthetic. See Carlson et al., 1946. hydroxy streptomycin, an antibiotic derived f r o m Streptomyces griseo-carneus exhibits an in vitro antibacterial spectrum similar to that of streptomycin. Its activity per mg when assayed against Bacillus subtilis is equivalent to 784 micrograms of streptomycin base. The empirical formula has been calculated as C21H39 NTOIS. Degradation experiments show the presence of the streptidine and N-methylglucosamine fragments of streptomycin. The streptose portion of the new antibiotic yields, instead of maltol, a crystalline product which is presumably 2-hydroxymethyl 3-hydroxy 1, 4pyrone; i.e., a hydroxylated maltol. The hydroxystreptomycin yields the hexa-acetate of a disaccharide while dihydrostreptomycin gives a penta-acetate. See Northern Regional Research Laboratory, U.S. Dept. of Agriculture, 1950; Benedict et al., 1950. Hygrophorus calyptraeformls, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus ceraceus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus chlorophanus, a fungus, extracts of the sporophores of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus ehrysodon, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus clnereus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus citrlnus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Hygrophorus coccineus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Hygrophorus conicus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus dlscoideus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus eburneus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus fornicatus, a fungus, extracts of the sporophores of which are ineffective in

C r o s s r e f e r e n c e s a r e indicated by SMALL CAPITALS

[145] vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus hypotbejus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus intermedhis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus lacmus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus laetos, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus miniatus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1. 2], and Pseudomonas aeruginosa [1]. See [1] Wilkins and Harris, 1944d; [2] Mathieson, 1946. Hygrophorns nemoreos, a fungus, extracts of the sporophores of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus nigrescens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus nitratus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus niveus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus obrusseus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus ollvaceo-albus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus penarius, a fungus, extracts of the sporophores of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus pratensis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus pratensis v. pallidus, a fungus, extracts of the sporophores of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus. See Wilkins, 1946a.

HYMENOCALLIS CAYMANENSIS

Hygrophorus psittacinus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus pnniceus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus real, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus real v. insipida, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus russocoriaceus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus sciophanus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Hygrophorus subradiatus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus unguinosus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hygrophorus virgineus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hymenaea verrucosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hymenanthera traversil, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hymenocallis sp., a higher plant, extracts of the bulbs of which are effective in the treatment of experimental malaria. See Spencer et al., 1947. Hymenocallis americana, a higher plant, extracts of the bulbs of which are effective in the treatment of experimental malaria. See Spencer et al., 1947. Hymenocallis calathina, a higher plant, aqueous extracts of the flower and leaf of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Extracts of the bulbs of this plant are slightly effective in the treatment of experimental malaria (2). See (1) Schnell and Thayer, 1949; [2] Spencer et al., 1947. Hymenocallis caribaea, a higher plant, extracts of the bulbs of which are effective in the treatment of experimental malaria. See Spencer et al.. 1947. Hymenocallis caymanensis, a higher plant, extracts of the bulbs of which are shgntly effec-

Cross references are indicated by SMALL CAPITALS

HYMENOCALLIS CORONARIA

[14«]

tive in the treatment of experimental malaria. See Spencer et al., 1947. Hymenocallis coronaria, a higher plant, extracts of the bulbs of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Hymenocallis galvestonensis, a higher plant, extracts of the bulbs of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Hymenocallis occidentalis, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Hymenocallis palmeri, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Hymenocallis rotata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Hymenochaete agghitinans, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be ineffective against these two microorganisms [2], See [1] Robbins et al., 1945; [2] Wilkins, 1948. Hymenochaete corrugata, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b) to be ineffective against these two microorganisms [2, 3]. See [1] Robbins et al., 1945; [2] Wilkins, 1948; [3] Wilkins, 1947b. Hymenochaete curtisii, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Robbins et al., 1945. Hymenochaete rubiginosa, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be ineffective against these two microorganisms [2,3]. Extracts of the sporophores of this fungus are ineffective against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa [4], See [1] Robbins et al., 1945; [2] Wilkins, 1946b; [3] Wilkins, 1947b; [4] Wilkins and Harris, 1944d. Hymenochaete tabacina, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1,2] and b) to be ineffective against these two microorganisms [3, 41. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1947b; [4] Wilkins, 1948. Hymenodictyon excelsum, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and in the treatment of experimental malaria [2], See [1] Osborn, 1943; [2] Spencer et al., 1947. Hymenomycetes, as test organisms in vitro, see DACTYLIUM

DENDROIDES.

Hyoscyamus niger, a higher plant, some extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Mycobacterium tuberculosis [1], and other extracts of which are ineffective against Staph, aureus and E. coli [2], See [1] Gottshall et al., 1949; [2] Osborn, 1943. Hypericum calycinum, a higher plant, extracts of which are effective in vitro against Mycobacterium tuberculosis but not against Staphylococcus aureus and Escherichia coli. See Gottshall et al., 1949. Hypericum elodes, a higher plant, aqueous extracts of which are effective in vitro against

Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Hypericum fragile, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Hypericum hirsutum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hypericum humifusom, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hypericum hyssopifolium, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hypericum moserianum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hypericum mutilum, a higher plant. Extracts of leaves, stems, and flowers are effective in vitro against Staphylococcus aureus and Escherichia coli [1]; extracts of the roots inhibit Staph, aureus but not E. coli [1, 2]. See [1] Carlson, Douglas, and Robertson, 1948; [2j Carlson and Douglas, 1948a. Hypericum olympicum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Hypericum patulum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hypericum perforatum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the leaves, stems, and flowers inhibit Staph, aureus and E. coli; extracts of the roots inhibit Staph, aureus but not E. coli [2]. Other extracts are reported to inhibit both Staph, aureus and E. coli [3]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [4], See [1] Osborn, 1943; [2] Carlson, Douglas, and Robertson, 1948; [3] Carlson and Douglas, 1948a; [4] Hayes, 1947. Hypericum polypbyllum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hypericum pulchrum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hypholoma appendiculatum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Hypholoma candolleanum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa [2], See [1] Wilkins, 1948; [2] Wilkins and Harris, 1944d. Hypholoma capnoides, a fungus which is weakly inhibitory in vitro for Staphylococcus aureus and/or Escherichia coli [1]. Extracts of the sporophores of this fungus are ineffective against Staph, aureus, E. coli, and Pseudo-

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[147]

ILEX BRONXENSIS

monas aeruginosa [2], See [1] Wilkins, 1948; [2] Wilkins and Harris, 1944d. Hypholoma dispersum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Wilkins, 1948; [2] Wilkins and Harris, 1944d. Hypholoma fasciculare, a fungus which is effective in vitro against Staphylococcus aureus a n d / o r Escherichia coli [1, 2], Extracts of the sporophores of this fungus are ineffective against Staph, aureus [3, 4], E. coli [3, 4], and Pseudomonas aeruginosa [4]. See [1] Wilkins, 1946b; [2] Wilkins, 1948; [3] Mathieson, 1946; [4] Wilkins and Harris, 1944d. Hypholoma hydrophilum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Hypholoma lachrymabandum, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Wilkins, 1946a. Hypholoma perplexum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Hypholoma sublateritium, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1,2] and b) to inhibit Staph, aureus and/or E. coli [3, 4], Extracts of the sporophores of this fungus are reported a) to inhibit Staph, aureus but not E. coli [5] and b) to be ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [6]. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1946b; [4] Wilkins, 1948; [5] Mathieson, 1946; [6] Wilkins and Harris, 1944d. Hntholoma velutinum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Wilkins, 1947c; [2] Wilkins and Harris, 1944d. Hypochaeris radicata, a higher plant, aqueous extracts of which are ineffective in vitro against

Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Hypochnus centrifugus, a fungus which is reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and b) to inhibit these two microorganisms [2]. According to the second investigator, the antibiotic action may be due to the production of acid [2], See [1] Wilkins, 1948; [2] Hervey, 1947. For further reference see Endo, 1931, 1932a, and 1932b. Hypochnus echinosporus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Hypochnus fumosns, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Hypochnus sasakli, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. For further reference see Endo, 1931, 1932a, 1932b. Hypochnus solani, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Hypochnus solani v. brassicae, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Hypochnus solani v. lactucae, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. hypopyon ulcers, experimental, see GRAMICIDIN. Hypoxylon coccineom, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporophores of this fungus are also ineffective against these two microorganisms [2], See [1] Wilkins, 1946b; [2] Wilkins, 1946a. Hyptis pectinata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Hyptis rhytidea, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Hyssopus officinalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. See also PHYTONCIDES.

Iheris amara, a higher plant, aqueous extracts of the seeds of which are effective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. Aqueous extracts of the flower, leaf, stem, root, and seedling are ineffective against these three organisms. See Schnell and Thayer, 1949. Iberis gibraltica, a higher plant, aqueous extracts of the seed of which are effective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Iberis sempervirens, a higher plant, aqueous extracts of the seed of which are effective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and the spores of Neurospora crassa [1]. See [1] Schnell and Thayer, 1949; [2] Osbom, 1943. Iberis "Superba," a higher plant, aqueous extracts of which are effective in vitro against

Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Iberis umbellata, a higher plant, aqueous extracts of the seed, flower, leaf, and root but not of the seedling of which inhibit in vitro the spores of Neurospora crassa. Only extracts of the seed inhibit Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Ilex aquifolium, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ilex bronxensis, a higher plant, ether, but not aqueous, extracts of the berry, leaf, and stem of which are effective in vitro against Escherichia coli. Only ether extracts of the stem inhibit Staph, aureus and only aqueous extracts of the berry and leaf inhibit the spores of Neurospora crassa. See Schnell and Thayer, 1949.

Cross references are indicated by SMALL CAPITALS

[148]

I L E X CASSINE

Hex c a a f a e , a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. D a condHna, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Dcz decidua, a higher plant, the fruit of which In vitro inhibits Staphylococcus aureus, Escherichia coli, and Erwinia carotovora, but does not inhibit Phytomonas tumefaciens. See Hayes, 1947. Ilex hudgnh, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ilex opaca, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Ilex opaca f. sobintegra, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Hex paraguarlensls, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [2]. See [1] Osborn, 1943; [2] Gottshall et al., 1949. Ilex scopolorls, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. nUckun anisatorn, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Impatient balsamina, a higher plant (the garden balsam), aqueous extracts of the seed, seedling, flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1], Other extracts of this plant inhibit Staph, aureus and Mycobacterium tuberculosis but not Escherichia coli [2], It is also the source of the antibiotic 2-METHOXY1, 4-NAPHTHOQUINONE.

See

[1]

Schnell

and

Thayer, 1949; [2] Gottshall et al., 1949. Impatlens biflora, a higher plant, aqueous extracts of the stem and root of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Other extracts of this plant inhibit Staph, aureus and E. coli [2], See [1] Schnell and Thayer, 1949; [2] Carlson, Douglas, and Roberson, 1948. Impatiens hawkeri, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Impatlens bolstil, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Impatiens bookeriana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Impatlens kewensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn 1943. Impatiens oliveri, a higher plant, aqueous extracts of which are effective in vitro against

Staphylococcus aureus and Escherichia coll. See Osborn, 1943. Impatiens pallida, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli [1], In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staphylococcus aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2]. See [1] Sanders et al., 1945; [2] Hayes, 1947. Impatiens parviflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Impatiens roylei, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. impetigo,

clinical,

see

BACITRACIN;

GRAMICI-

DIN S. Indigofera potaninil, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. infectious mononucleosis, clinical, see AUREOMYCIN;

PENICILLIN.

Influenza. 1 Clinical, see AUREOMYCIN; PENICILLIN; STREPTOMYCIN. 2 E x p e r i m e n t a l , s e e ANTIBIOTIC H - 3 ; AUREOMYCIN; CHLORAMPHENICOL; PROTOANEMONIN; STREPTOTHRICIN; TEA; TERRAMYCIN.

influenzal meningitis, clinical, see AUREOMYCIN. Inga punctata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Inga vulpina, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ingenhousla triloba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Inhibin, a substance obtained from honey. See also URINE.

Inocybe sp., a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Inocybe asterospora, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe auricoma, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe boltonii, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe cookei, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe corydallna, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli,

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[149] and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe deciplentoides, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe deglubens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe descissa, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe fastigiata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe fulvella, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe geophylla, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe geophylla v. lilaclna, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe godeyi, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe griseo-lilaclna, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe hirsute, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Inocybe hystrix, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe incarnate, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe lacera, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe longicystls, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Iiocybe luctfoga, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli,

INOLOMIN

and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe maculate, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coll and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe cf. murrayana, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Inocybe napipes, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe obscura, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe ovato-cystis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe petiginosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe praetervlsa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe pyriodora, a fungus, extracts of the sporophones of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe rlmosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Inocybe serrata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Inocybe striata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inocybe tomentosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Pseudomonas aeruginosa [1]. See [1] Wilkins and Harris, 1944d; [2] Mathieson, 1946. Inocybe umbrina, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Inoloma tragannm, see INOLOMIN. inolomin, an antibiotic substance which is obtained from the fungus Inoloma traganum. It is isolated by crushing the fresh young fungi, extracting with water, and removing the colloidal material with ammonium sulphate and the coloring matter with carbon. The activity is then adsorbed on carborafine, eluted with ethanol, and concentrated in vacuo. The product is a yellow, glassy material soluble in water

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

INSECTICIN

[150]

and in phosphate buffer at p H 7. It is stable on standing at rm. temp, but darkens and loses its activity on autoclaving. Inolomin inhibits only certain micrococci and pseudodiphtheriae. Mice weighing 16-20 gm are unaffected by single i.v. injs of 1 cc of a 10% solution of this agent. See Fragner, 1949. insecticin, an antibiotic substance obtained from the blood of the insects Bombyx, a genus of silkworm moths; Dasychyra pudibunda; Galleria metlonella, the bee moth; Macrothylaria rubi; and Sphinx ligustri; but not from the blood of Apis mellifica, the honey bee. lnsecticin inhibits the following microorganisms in vitro: Brucella abortus Corynebacterium diphtheriae Gonococci Hemolytic staphylococci Meningococci Mycobacterium gallinaceus Pneumococci Salmonella enteritidis Salmonella paratyphi Salmonella typhi Streptococci. See Rehm, 1948. Inula helenhim, a higher plant. Extracts of the root are effective in vitro against Staphylococcus aureus and Escherichia coli. Extracts of the leaves and stems inhibit Staph, aureus and not E. coli. Extracts of the flowers inhibit E. coli and not Staph, aureus [1], Extracts of the entire plant are ineffective against Staph, aureus and E. coli [2], See [1] Carlson, Douglas, and Robertson, 1948; [2] Osborn, 1943. Inula bookeri, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Inula salicina, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Inula splraeifolia, a fungus, an extract of which is effective in vitro against Staphylococcus aureus, Bacillus anthracis, and Corynebacterium xerosis but does not affect Escherichia coli and Pseudomonas pyocyanea. The empirical formula of this substance is C10H12O3; its m.p., 185°-186°C. It is slightly soluble in water and petroleum ether and very soluble in acetone. See Osborn et al., 1947, unpublished; Abraham and Jennings, 1947, unpublished. Iodanthus pinnatifidus, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. iodinin, an antibiotic bacterial pigment isolated from Chromobacterium iodinum. It is the N, Ni-dioxide of a dihydroxyphenazine:

It is effective in vitro against Proteus vulgaris, Salmonella typhi. Staphylococcus aureus, and Streptococcus hemolyticus, and ineffective against Escherichia coli. See Mcllwain, 1941. Ionopsidium acaole, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Ipomoea batatas, a higher plant, the sweet potato, which produces one or more antibiotic substances and possibly a substance which stimulates the growth of bacteria and fungi. Aqueous extracts of all parts of fusaria-wiltresistant sweet potatoes and of the tubers and stems of susceptible plants stimulate Fusarium oxysporum f. batatas, F. oxysporum f. lycopersici, Escherichia coli, and Staphylococcus aureus and are without effect on Mycobacterium phlei. Aqueous extracts of wilt-susceptible sweet-potato leaves and roots and water-insoluble residues from all parts except the tubers of resistant plants are slightly inhibitory for F. oxysporum i. batatas. Antibacterial activity is shown by the water-soluble residue resulting from methanol extraction of dried and ground parts of both wilt-susceptible and resistant plants. However, only extracts of the stems of wilt-susceptible plants inhibit Myco, phlei. Various partially purified extracts of the stems of wilt-susceptible plants inhibit the following microorganisms: Bacillus cereus Bacillus subtilis Escherichia coli Fusarium oxysporum f. batatas Fusarium oxysporum f. lycopersici Mycobacterium phlei Rhodococcus roseus Sarcina lutea Serratia marcescens Staphylococcus aureus Xanthomonas translucens f. sp. hordei-avenae This antibacterial action is accompanied in many cases by stimulation of the test organism [1]. It is also reported that aqueous extracts of I. batatas are ineffective in vitro against Staph, aureus and E. coli [2], See [1] Bruchner et al., 1949; [2] Osborn, 1943. Ipomoea bona-nox, a higher plant, aqueous and ether extracts of the leaf, stem, and root of which are effective in vitro against Staphylococcus aureus. All these extracts except the ether extract of the root inhibit the spores of Neurospora crassa; none of the extracts inhibits Escherichia coli. See Schnell and Thayer, 1949. Ipomoea coccinea, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Ipomoea digitata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ipomoea horsfalliae v. briggsii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ipomoea learii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Osborn, 1943. Ipomoea pandurata, a higher plant, extracts of which are effective in vitro against Staphylo-

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[1511 coccus aureus but not against Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Ipomoea purpurea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Iresine sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Iris spp., various unidentified spp. of the genus of higher plants Iris. Extracts of some are ineffective in vitro against Bacillus subtilis and Escherichia coli [1]. Extracts of others are ineffective in vivo against experimental malaria [2]. See [1] Sanders et al., 1945; [2] Spencer et al., 1947. Iris, Chinese, a higher plant, aqueous extracts of the leaf of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Iris, common, a higher plant, aqueous extracts of the leaf of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Iris douglasiana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Iris, Dutch, a higher plant, aqueous extracts of the leaf, root, and bulb of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Iris, fragrant, a higher plant, aqueous extracts of the leaf of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Iris germanica, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [3]. See [1] Gottshall et al., 1949; [2] Osborn, 1943; [3] Hayes, 1947. Iris orcbidioides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Iris pseudacorus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Iris reticulata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Iris rubro-marginata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Irpex cinnamomeus, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], This antibacterial activity may be due to the production of acid [1]. The fungus is also reported to be ineffective against Staph, aureus and E. coli [3]. See [1] Hervey, 1947; [2] Robbins et al., 1945; 13] Wikins, 1947b. Irpex destruens, a fungus, the culture media of which are strongly inhibitory in vitro for Staphylococcus aureus and/or Escherichia coli. See Wilkins, 1947a. See also DESTKUIN.

IXORA AURORA

Irpex mollis, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to inhibit both these microorganisms [2]. The liquid culture medium of this fungus inhibits Staph, aureus in dilutions of 1:1,024 [2J. The culture medium is also reported to inhibit Staph, aureus and E. coli [3]. See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1947b. Irpex obliquus, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores of this fungus are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Wilkins, 1948; [2] Wilkins and Harris, 1944d. Irpex pacbyodon, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Irpex zonatus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Irvingia gabonensis, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Irvingia smithii, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Isanthus brocbiatus, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Isatis tinctoria, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Isoloma bogotensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Isoloma hirsotum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Isonandra gutta, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Isotoma longifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ithyphallus sp., a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1]. It is also reported to be ineffective against these microorganisms [2]. See [1J Robbins et al., 1945; [2] Wilkins, 1947b. Iva frutescens, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Iva imbricata, a higher plant, aqueous extracts of the fruit and leaf of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Ixora amabilis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ixora aurora, a higher plant, aqueous extracts of which are ineffective in vitro against Staph-

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IXORA COCCINEA

[152]

ylococcus aureus and Escherichia coli. See Osborn, 1943. Ixora coccinea, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Ixora «triam, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ixora macrothyrsa, a higher plant, aqueous extracts of which are effective in vitro against .Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ixora pilgrim!, a higher plant, aqueous extracts of the garden hybrid of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ixora plumea, a higher plant, aqueous extracts

of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ixora spectabilb, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ixora stricta v. alba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ixora westii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. iztacpatti, common name of a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947.

Jacaranda ovaltfolia. a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Jacobinia chrysostephana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Jacobinia floribunda, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Jacobinia magnifica v. carnea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Jacobinia moblntle, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Japanese encephalitis virus. 1 As test organism in vitro, see SERUM. 2 Experimental infections,

Jateorhlra cohunba, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Jatropha gossypifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Jatropha herbacea, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Jatropha multifida, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Jatropha pandurifolla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Jatropha urens, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. javanicin, a red crystalline antibiotic occurring in the culture filtrates of the mold Fusarium javanicum [1], It is extracted from the filtrate with ether or benzene and removed from the organic solvent with sodium carbonate. Javanicin is a weak monobasic acid. Its m.p. is 208°C. (decomp.). The empirical formula is CISHMOS [1]. It is regarded as 5:8-dihydroxy6 acetonyl-1:4-naphthoquinone carrying additional ß-methyl and /3-methoxyl groupings [2, 3]:

see

CHLORAMPHENICOL.

Jasione perennis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Jasmlnum azoricum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Jasminum frnticans, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Jasminum maingayi, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Jasminum parkeri, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Jasminum rex, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Jasminnm sambac, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943.

CHaCO

Also occurring in the culture filtrates of this fungus is the active crystalline substance oxyjavanicin, CI.-,HH07, which has a m.p. of 212 C C. [1]. It appears to form a molecular

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[153]

KALANCHOE FLAMMEA

The compound is a yellow substance, melting at 155 C. Although it is insoluble in water, it is soluble in aqueous solutions of sodium hydroxide and hot acetic acid; and is very soluble in chloroform. The empirical formula is C10H6O3 and the structural formula is 5-hydroxy-l, 4, naphthoquinone. TOXICITY.—Juglone has been reported as being toxic to fish and to the noncutinized surfaces of root tissues. EXPERIMENTAL CLINICAL RESULTS, HUMAN BEINGS.—Juglone is reported to be effective when applied locally to persistent ringworm (Microsporum audouini, Trichophyton sp., Tinea) infection. The use of the green husks of the black walnut for control of ringworm can be traced back to the Greeks and Romans. Brissemoret and Michaud (1917) recorded the effective clinical use of juglone against eczema, psoriasis, impetigo, and other skin diseases. It has also been shown that the antibiotic is effective in terminating the growth of germinating fungus spores. See Gries, 1943; Brissemoret and Michaud, 1917. Juncus communis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Juniperus communis, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [1], See 11] Gottshall et al., 1949; [2] O s b o m , 1943. Juniperus borizontaiis, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Juniperus occidentals, a higher plant (the jumper), extracts of which are effective in vitro against Staphylococcus aureus. Twoweek-old chicks injected with the extracts mixed with blood containing Plasmodium gallinaceum fail to develop malaria. However, the extracts are ineffective in the treatment of experimental malaria in chicks and Diplococcus pneumoniae infections in mice. Doses of 0.5 to 1.0 cc. injected i.p., s.c., or i.v. in chicks and mice are lethal. See Carlson et al., 1946. Juniperus thurifera, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Jupunba trapezifoiia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Jussiena longifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

compound with javanicin having a m.p. of 178°C. Javanicin is ineffective in vitro against Bacterium tumefaciens, Pseudomonas jluorescens, and Ps. aeruginosa and is effective against Bacillus subtilis, Bacl. fascians, Clostridium welchil, Escherichia coli, Mycobacterium phlei, Myco, tuberculosis hominis, Staphylococcus aureus, Streptococcus hemolyticus, and Strep, pyogenes [1, 2]. It is bactericidal for Myco, tuberculosis hominis in c o n c e n t r a t i o n s of 1:50,000-1:100,000 [1]. This action is not affected by the presence of serum [1], but Strep, hemolyticus is not inhibited by javanicin when grown on a blood medium [2]. The maximum tolerated dose in mice i.p. is 10 mg. Local treatment of tuberculous ulcers in guinea pigs shows only minimal therapeutic effects [2]. See [1] Arnstein et al., 1946b; [2] Arnstein et al., 1946a; [3] Arnstein and Cook, 1947. Jeffersonia dlphylla, a higher plant, various extracts of which are ineffective in vitro against Bacillus subtilis [1], Escherichia coli [1, 2], Staphylococcus aureus [2], and Mycobacterium tuberculosis [2]. See [1] Sanders et al., 1945; [2] Gottshall et al., 1949. Joannesia princeps, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See O s b o m , 1943. Juanuiloa aurantiaca, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Juglans cinerea, see JUGLONE. Juglans nigra, a higher plant, extracts of which are effective in vitro against Bacillus subtilis but not against Escherichia coli. See Sanders et al., 1945. See also JUGLONE.

Juglans regia, a higher plant, aqueous extracts of the commercial wood obtained from which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Bacillus anthracis. See Sanchez et al., 1948. See also JUGLONE. Juglone, an antibacterial and antifungal substance obtained from Juglans nigra, J. cinerea, and J. regia (species of black walnut). The antibiotic may be found in the fresh, green husk, in the bark, or in other plant parts. Since juglone is rapidly reduced, it is impossible to extract juglone from the dried plant without first reoxidizing the plant parts.

K Kadsura japonica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Kageneckla oblonga, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947.

Kalanchoe connata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Kalanchoe flammea, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobac-

Cross references are indicated by SM ILL CAPITALS

KALANCHOE QUARTINIANA

[154]

terium tuberculosis. See Gottshall et al., 1949. Kabnchoe qnarttntona, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Kaimig angostifolla, a higher plant, ether extracts of the berry and leaf and aqueous extracts of the stem of which are effective in vitro against Escherichia coli, while aqueous extracts of the leaf are ineffective. Only aqueous extracts of the berry inhibit Staphylococcus aureus, and only aqueous extracts of the leaf inhibit the spores of Neurospora crassa. See Schnell and Thayer, 1949. Kalmlopsls leechiana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. keratitis, clinical, see AUREOMYCIN. keratoconjunctivitis, clinical, see AUREOMYCIN; BACITRACIN; PENICILLIN;

STREPTOMYCIN.

Kerria japonica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Kirkia acuminata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Kitaibelia vitifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Klainedoxa gabonensis, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Klainedoxa grandifolia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Klebsiella spp., as test organism in vitro, see POLYMYXINS; TYROCIDINE.

Klebsiella pneumoniae. 1 As test organism in vitro, s e e ANTIBIOTIC H - 3 ; ANTIBIOTIC X G ; ANTISMEGMATIS FACTOR; ASPERGILLIC ACID; ASTASIA KLEBSEII; AUREOMYCIN; BACILLUS MESENTERICUS; BIFORMIN; BIFORMIC ACID; BORRELIDIN; CENTAUREA MACULOSA; C H I L O M O N A S PARAMEC I U M ; CHLORAMPHENICOL; CIRCULIN; CLAVACIN; C O P T I S CHINENSIS; ESCHERICHIA COLI; EUGLENA GRACILIS; FUMIGACIN; GLIOTOXIN; GRISEIN; HIRSUTIC ACIDS; K O J I C ACID; LUPULON AND H U MULON; 5-METHOXY-P-TOLUQUINONE; MYCOPHENOLIC ACID; MYCOSUBTILIN; N E O M Y C I N ; NIDULINE; O N C O P E L T U S FASCIATUS; PENATIN; P E N ICILLIC ACID; PENICILLIN; PERSOONIA PINIFOLIUS; PLEUROTIN; POLYMYXINS; P O L Y P E P T I N ; PROTOA N E M O N I N ; PSALLIOTA XANTHODERMA; PSEUDOMONAS FLUORESCENS; R H E I N ; SPINULOSIN; STREPTOMYCES AUREOFACIENS; STREPTOMYCES VENEZUELAE; STREPTOMYCIN; STREPTOTHRICIN; SUBTENOLIN; SUBTILIN; SULFACTIN; TERRAMYCIN; TETRAHYMENA GELEII; TETRAHYMENA VORAX; T H U J A PLICATA; TYROTHRICIN; USNIC ACID;

Kneiffia fruticosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Kneiffia linearis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Kneiffia pumila, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Kniphofia uvaria, a higher plant, aqueous extracts of the seedling of which are effective in vitro against the spores of Neurospora crassa and are ineffective against Staphylococcus aureus and Escherichia coli [1], Other aqueous extracts of this plant also are ineffective against Staph, aureus and E. coli [2]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Kochia tricophylla, a higher plant, ether extracts of the stem and root of which are effective in vitro against Escherichia coli, while aqueous extracts of the seed, seedling, stem, and root, and ether and aqueous extracts of the leaf are ineffective. None of these extracts inhibits Staphylococcus aureus and the spores of Neurospora crassa. See Schnell and Thayer, 1949. kojic acid, a crystalline antibacterial substance isolated from the culture media of the following: Acetobacter, spp. [1] Aspergillus sp. [5] Aspergillus albus [1,2] Aspergillus alliaceus [3] Aspergillus awamori [1] Aspergillus Candidus [1,2] Aspergillus clavatus [1] Aspergillus effusus [1,2] Aspergillus flavus [1,2] Aspergillus fumigatus [1] Aspergillus giganteus [1] Aspergillus glaucus [1] Aspergillus gyrnnosardae [1] Aspergillus luteo-virescens [4] Aspergillus nidulans [1,2] Aspergillus oryzae [1,2] Aspergillus parasiticus [1,2] Aspergillus tamarii [1,2] Aspergillus wentii [3] Pénicillium chrysogenum [4] Pénicillium dalae [1,2] Kojic acid is extracted by refrigerating the culture filtrate and recrystallizing from hot water or by vacuum sublimation [5]. The m.p. is 152 C C. Kojic acid is 5-hydroxy-2-hydroxymethyl-y-pyrone [1]:

USTIN. 2 E x p e r i m e n t a l infections, see ACTINO-

Î

RUBIN; AUREOMYCIN; BORRELIDIN; CHLORAMPHENICOL; LAVENDULIN; POLYMYXINS; STREPTOM Y C I N ; TERRAMYCIN; TYROCIDINE; TYROTHRI-

OH

CIN. 3 Treatment of clinical infections caused

b y , s e e PENICILLIN; STREPTOMYCIN.

Kleinia neriifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherchia coli. See Osborn, 1943. Kloeckera apiculata, as test organism in vitro, see

ACTIDIONE.

CHjOH -

I II C ^ H o

The activity of kojic acid is unaffected by incubating for 3 hr at 37°C. with 50% serum [2],

C r o s s references are indicated by SMALL CAPITALS

[155] SPECTRUM — Inhibitory concentration Organism Aerobacter 1:500-1:1,000 [4] aerogenes Alcaligenes fecalis 1:500 [4] Bacillus anthracis 1:500-1:1,000 [4] Bacillus megatherium 1:1,000 [4] Bacillus 1:500 (partial inhimesenlericus bition) [4] Bacillus mycoides 1:500 [4], 2.5 rag/cc [6] Bacillus novus 1:1,000 [4] Bacillus subtilis 1:500 (partial inhibition) [4], 0.62 m g / c c [6] Brucella abortus 1:4,000 [4] Brucella melilensis 1:2,000 [4] Brucella suis 1:4,000 [4] Chromobacterium indicum 1:500 [4] Chromobacterium violaceum 1:2,000 [4] Clostridium 1:500 (partial inhibibotulinum tion) [4] Clostridium no inhibition at 1:500 histolyticum [4] Clostridium novyi 1:500 [4] Clostridium no inhibition at 1:500 perfringens [4] Clostridium 1:500 (partial inhibiputrificum tion) [4] Clostridium no inhibition at 1:500 [4] sporogenes Clostridium tetani no inhibition at 1:500 [4] Corynebacterium no inhibition at 1:500 diphtheriae [4] Corynebacterium 1:500 (partial inhibixerosis tion) [4] Diplococcus pneumoniae 1:500-1:2,000 [4] Escherichia sp. 1:500 [4] Escherichia coli 1:400-1:800 [2], 1:2,000 [4], 2.5 m g / c c [6] 1:500-1:1,000 [4] Gaffkya tetragena 1:500-1:1,000 [4], Klebsiella 0.62 mg/cc [6] pneumoniae Leptospira canicola 1:1,000,000 [4] Leptospira icterohemorrhagiae 1:100,000 [4] Micrococcus 1:500 (partial inhibiaurantiacus tion) [4] Micrococcus roseus 1:500 [4] Mycobacterium phlei 2.5 mg/cc [6] Mycobacterium smegma 0.31 mg/cc [6] Neisseria catarrhalis 1:2,000-1:4,000* [4] Neisseria no inhibition at 1:2,000 gonorrhoeae [4] Neisseria no inhibition at 1:2,000 intracellulars [4] Neisseria perjlava no inhibition at 1:2,000 [41 Neisseria sicca no inhibition at 1:2,000 [4] Pasteurella axicida no inhibition at 1:4,000 [4] Pasteurella no inhibition at 1:4,000 boviseptica [4] Pasteurella caviae no inhibition at 1:4,000 [4] no inhibition at 1:4,000 Pasteurella equiseptica [4] Pasteurella no inhibition at 1:4,000 oviseptica [4]

KYLLINGIA MONOCEPHALA Organism Pasteurella pestis Photobacterium fischeri Proteus sp. Proteus mirabilis Proteus vulgaris Pseudomonas aeruginosa Pseudomonas fluorescens Salmonella aertrycke Salmonella cholerae-suis Salmonella enteritidis Salmonella paratyphi Salmonella pullorum Salmonella schottmuelleri Salmonella typhi

Inhibitory concentration 1:4,000 [4] 2.5 m g / c c [6] 1:400-1:800 [2] 1:500 [4] 1:500 [4] 1:6,000-1:6,400 [2], 1:500 [4], 5 m g / c c [6] 1:2,000 [4] 1:1,000 [4] 1:500 [4] 1:400-1:800 [2], 1:500 [4] 1:500-1:1,000 [4] 1:1,000 [4]

1:500 [4] 1:800-1:1,600 [2], 1:500-1:1,000 [4] Sarcina lutea 1:1,000 [4] Serratia marcescens 1:500 [4] Shigella dysenteriae 1:500-1:2,000 [4] Shigella paradysenteriae 1:500 [4] Spirillum rubrum 1:1,000 [4] Staphylococcus 1:500 (partial inhibition [4] albus 1:800-1:1,600 [2], Staphylococcus 1:500 [4], 1.25 m g / c c aureus [6] Staphylococcus 1:500 (partial inhibicitreus tion) [4] Streptococcus, alpha 1:500 [4] Streptococcus, beta 1:500 [4] Streptococcus no inhibition at 1:500 fecalis [4] Vibrio comma 1:2,000 [4] Vibrio metchnikovii 1:2,000 Vibrio proteus 1:4,000 [4] Vibrio schuykilliensis 1:2,000 [4] TOXICITY.—A 1% solution of kojic acid is lethal to human leucocytes within 3 hr; a 1:400 solution is without effect. The lethal i.v. dose in rats, dogs, and rabbits is 1 g m / k g , although 150 m g / k g produces toxic symptoms. In mice weighing 20-23 gm the toxic dose sc., i.p., or i.v. is 5 mg; the lethal dose is 30-40 mg; by mouth 80 mg doses are fatal [2], Other reports give the i.p. M L D for 17 gm mice as 30 mg [4], See [ l j Prescott and Dunn, 1940; [2] Jennings and Williams, 1945; [3] Gill-Carey, 1949b; [4] Morton et al., 1945; [5] Yuill. 1948; [6] Kavanaugh, 1947b. Kopsia fruticosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Krigia amplexicaulis, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. KylUngia monocephala, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Cross references are indicated by SMALL CAPITALS

LABURNUM VULGARE

[156]

Laburnum vulgare, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Laccaria laccata, a fungus, extracts of the sporophores of which are reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Mathieson, 1946; [2] W ilk ins and Harris, 1944d. Laccaria laccata, v., a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Laccaria laccata v. amethystina, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Laccaria laccata v. proxima, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Laccaria tortiiis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lachenalia tricolor, a higher plant, aqueous extracts of the bulb of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Lachnea cretea, a fungus, the culture media of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1943a. Lachnocladhim sp., a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Lactarhu aspideus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius blennhis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius camphoratus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius chrysorrheus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius cimicarhis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius controversos, a fungus, extracts of the sporophores of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d.

Lactarios deliciosas, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus (1,2), Escherichia coli [1], and Pseudomonas aeruginosa. See [1] Wilkins and Harris, 1944d; [2] Mathieson, 1946. See also L A C T A R O V I O L I N . Lactarius flexnosus, a fungus, extracts of the sporophores of which are ineffective In vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Lactarius fuliginosas, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius giyciosmns, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius insulsas, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius mitissimus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius pallidus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius pipera tus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius piperatus v. pergamenns, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius pubescens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius pyrogalus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius quietus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius rufus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius scrobicuiatos, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarius serifluus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli,

Cross rcferenccs are indicated by

SMALL

CAPITALS

[157] and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarios spinosulsus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarios subdulcls, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarios thetogalos, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarios torminosus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarios trivialis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarios torpis, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarios vellereos, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarios vie tus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarios volemos, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lactarios zooarios, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. lactaroviolin, a violet-red pigment isolated from Lactarius deliciosus. It is said to inhibit growth of a pathogenic human strain of tubercle bacilli in vitro. It melts at 53°C. It is very soluble in common organic solvents and reacts with carbonyl group reagents. The probable structural formula is: — — — —

5H CHs CHs C = CHa CHs

See Willstaedt and Zetterberg, 1946. lactenin (milk), found to contain several thermolabile bactericidal substances and two thermostable factors which inhibited lactobacilli. See Orla-Jensen and Snog-Kjaer, 1940. Lactobacillus spp., as test organisms in vitro, see

NISIN.

Lactobacillus acidophilus. 1 As test organism in vitro,

see

BACILLUS

sp.,

BACILLUS

LAMIUM ALBUM

GRAMICIDIN;

TYROCIDINE.

a n i m a l s , see TYROTHRICIN.

2

In

experimental

Lactobacillus arabinosos, as test organism vitro,

in

s e e D-LEUCINE; PROTAMINE ZINC I N S U L I N .

Lactobacillus bolgaricos, as test organism in vitro, s e e BACILLUS s p . , PERSOONLA PSALLIOTA XANTHODERMA.

PINIFOLIUS;

Lactobacillos easel, as test organism in

vitro,

s e e BACILLUS s p . , GLIOTOXIN; LYCOMAKASMINE; PERSOONIA PINIFOLIUS; PSALLIOTA XANTHODERMA; STREPTOTHRICIN; SUBTILIN.

Lactobacillus delbruckii, as test organism vitro,

in

see SUBTILIN.

Lactobacillos fermenti, as test organism in vitro, see

SUBTILIN.

Lactobacillos helveticos, as test organism vitro,

in

see SUBTILIN C .

Lactobacillus pcotosus, as test organism in vitro, see

SUBTILIN.

Lactuca bourgaei, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Lactoca canadensis, a higher plant, aqueous extracts of which show little or no inhibition ot growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Lactuca floridana, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Lactuca hastata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Lactuca muralis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lactuca perennis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lactuca plomieri, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Lactoca satlva, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lactoca virosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lafoensia vandeliiana, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Lagerostroemia indica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lagerostroeoiia indica v. alba, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osbom, 1943. Lagunaria patersonii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Lamlum albom, a higher plant, aqueous extracts of which are ineffective in vitro against

VULGATUS;

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

L A M I U M GALEOBDOLON

[158]

Staphylococcus aureus and Escherichia coli. See Osborn, 1943. I j m i n m galeobdolon, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ijiminm macalatnm v. camenm, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. I amhim orvala, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. I a m him purpureum, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Landolphla florida, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Landolphla klainii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. I .an tana camara, a higher plant, aqueous extracts of the stem and leaf but not of the seed and flower of which are effective in vitro against Escherichia coli. Only aqueous extracts of the leaf inhibit Staphylococcus aureus and the spores of Neurospora crassa [1]. Other aqueous extracts of this plant are ineffective against Staph, aureus and E. coli [2], and yet other extracts are ineffective in the treatment of experimental malaria [3]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943; [3] Spencer et al., 1947. Lantana camara v. alba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lantana camara v. delicatissima, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lantana indica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lantana involucrata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Lapageria rosea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Laplacea sp., a higher plant, extracts of the bark of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Laportea canadensis, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Lapsana communis, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. La rix decidua (European larch), a hot water extract of which in vitro inhibits Polyporus

schweinitzi, Poria xantha, and Fomes annosus. See Cartwright, 1942. L a m a divericata, a higher plant, also known as Covillea tridentata, which produces the ant i b i o t i c , NORDIHYDROGUAIARET1C ACID.

laryngotracheltis,

experimental,

see CHLORAM-

PHENICOL.

laryngo-tracheo-bronchitis, clinical, see PENICILLIN;

STREPTOMYCIN.

Laschia fusca, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. laterltiins, two antibacterial substances produced by species of the fungus genus Fusarium. Lateritiin I, CKHIOOINJ, which has a m.p. of 121°-122°C., is produced by f . lateritium. Lateritiin II, also CIKHIGOTN^., m.p. 125°C., is obtained from F. sp. (probably lateritium). The active principles are colorless, optically active, neutral, sparingly soluble in water, and very soluble in organic solvents. They are stable to mineral acids and to heat and unstable to alkalis. Both are active in vitro against Bacillus subtilis, Mycobacterium phlei, Staphylococcus aureus, and Streptococcus pyogenes. In addition, lateritiin I is effective at 1:160,000 to 1:640,00>0 against Myco. tuberculosis and has low toxicity for mice on i.p. inj. See Cook et al., 1947. laterosporin A and B, two antibiotic substances produced by the bacterium Bacillus laterosporus. The active principles are isolated by adjusting the culture fluid to p H 2, adsorbing on charcoal, eluting with acidified butanol, and extracting with ether and water. T h e water concentrate is adjusted to pH 6.8-7.0 and the activity is precipitated by the addition of picric acid. The picrate is then converted to the hydrochloride by suspending in alcohol containing hydrochloric acid. The acid-alcohol insoluble portion is laterosporin B. It is purified by dissolving in hydrochloric acid containing sodium chloride, extracting with butanol, and precipitating with ether. The product is a cream-colored powder. Laterosporin A, a lightbrown powder, is precipitated from the acidalcohol solution by the addition of ether. Both substances appear to be peptides and both are soluble in water. Laterosporin A is not destroyed by trypsin and is stable to boiling for one half-hour in the pH range 2-8. It dialyzes through a cellophane membrane. The standard is laterosporin A hydrochloride, 1 mg containing 10 units. Horse serum reduces the activity of both substances. SPECTRUM.—The following microorganisms are inhibited in vitro by these agents: Inhibitory concentration Microorganism units/cc LateroLaterosporin A sporin B Corynebacterium diphtheriae gravis 0.12 0.12 Corynebacterium xerosis 0.005 0.003 Escherichia coli 0.6 0.6 Mycobacterium phlei 0.0008 0.0004 Mycobacterium smegma 10.0 10.0 Mycobacterium 1.0 1.0 tuberculosis hominis (partial) (partial) Pseudomonas aeruginosa 5.0 10.0

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

LENTINUS CYATHIFORMIS

[159]

Microorganism

Inhibitory concentration units/cc LateroLaterosporttl A sporin B 1.2 2.5 0.6 0.6 0.01 0.01 0.01-0.12 0.01-0.12

Salmonella enteritidis Salmonella typhi Staphylococcus aureus Streptococcus pyogenes See Barnes, 1949. Lathyrus aurantfas, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lathyrus latifolius, a higher plant, aqueous extracts of the seed and entire plant of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. Aqueous extracts of the entire plant are ineffective against the spores of Neurospora crassa. See Schnell and Thayer, 1949. Lathyrus odoratus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lathyrus silvester, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lathyrus vernus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Latuca sativa, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Laugeria resinosa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Laurelia aromatica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Laurelia nova-zealandi, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lauras nobilis, a higher plant, various extracts of which are reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be ineffective against Staph, aureus, E. coli, and Proteus X-19 [2], See [1] Osborn, 1943; [2] Cardoso and Santos, 1948. Lauras nobilis v. angustifolium, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lavandula iatifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lavatera occidentals, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. lavendulin, an antibiotic substance which is obtained from an unidentified Actinomyces which resembles A. lavendulae. It has been designated as Actinomyces A-10. The active principle is partially purified by cation adsorption followed by treatment with sodium chloride, boiling methanol, ether, and absolute ethanol.

Final purification is effected by chromatographic adsorption on an alumina column. Possible formulae for the helianthate are: CMH.;:IOI»NI3S:>,

GI.H^OIUNNSJ,

and

Cir.H2o

O.iNiS. The m.p. of the helianthate is 212°220°C. (corr., decomp.) [1], "The smallest amount of the antibiotic per ml of nutrient agar which suppresses growth of E. coli under conditions of the test is called one dilution unit" [1]. Staphylococcus aureus is inhibited in vitro by 0.65-0.78 micrograms/cc [2], TOXICITY.—la mice weighing 17-19 gm, 0.1 mg i.v. causes no deaths; 0.25 mg is lethal for 509r of the test animals in 6 days, while 0.5 mg kills 100% in 125 hr. Survivors of large doses show weight loss or failure to gain weight. On autopsy there is evidence of damage to kidney and liver and reduction in the size of the thymus and spleen. In some cases there are signs of recovery f r o m the liver damage [2]. EXPERIMENTAL CLINICAL RESULTS. —Intravenous inj of 25 micrograms/17-19 gm mouse is regarded as the protecting dose against Klebsiella pneumoniae infection when the infecting inoculum is 10,000 M L D . See [1] Junowicz-Kocholaty and Kocholaty, 1947; [2] Morton, 1947a. Lawsonia inermis, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lecanora sordida, a lichen which produces the a n t i b i o t i c ROCCELUC ACID.

Lechea villosa, a higher plant, extracts of the upper stems and fruit of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Ledenbergia rosea-aenea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Leea angulata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Leishmania, as test organism in vitro see TRYPANOTOXIN.

Leishmania donovani, as test organism in s e e PROACTINOMYCIN; LATINE.

STREPTOMYCIN;

Leishmania tropica, as test organism in s e e BERBERINE; BELLATINE.

GRAMICIDIN;

vitro,

UMBEL-

TYROCIDINE;

vitro, UM-

Lemna minor, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and in vivo against experimental malaria [2], See [1] Osborn, 1943; [2] Spencer et al., 1947. Lentinus cochleatus, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. The culture media of this fungus are weakly inhibitory for Staph, aureus a n d / o r E. coli [2], Extracts of the sporophores are reported a) to inhibit Staph, aureus and E. coli [3] and b) to inhibit Staph, aureus but not E. coli and Pseudomonas aeruginosa [4], See [1] Hervey, 1947; [2] Wilkins, 1947; [3] Mathieson, 1946; [4] Wilkins and Harris, 1944d. Lentinus cyathiformis, a fungus which is weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1948.

C r o s s references are indicated by SMALL CAPITALS

LENTINUS DEGENER

1160]

L c n t k n s degener, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. It is also one of the sources of antibiotic S - M E T H O X Y - P - T O L U Q U I N O N E . See Hervey, 1947. L c n t t a u bepatotricbasL, a funpus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coll. See Mathieson, 1946. Lentfcnu kanffmanil, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1], It is also reported to be weakly inhibitory against Staph, aureus a n d / o r E. coli [2]. See [1] Hervey, 1947; [2] Wilkins, 1947b. Lentlniu lepklens, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1], b) to inhibit Staph, aureus and/or E. coli [2, 3], and c ) to be ineffective against these two microorganisms [4], The culture media of this fungus are weakly inhibitory for Staph, aureus a n d / o r E. coli [5]. Extracts of the sporophores are ineffective against Staph, aureus and E. coli [6], See [1] Robbins et al., 1945; [2] Wilkins, 1946b; [3] Wilkins, 1947b; [4] Hervey, 1947; [5] Wilkins, 1947a; [6] Wilkins, 1946a. See also P I N O S Y L V I N E . Lenttaras praerigMas, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947a. Lentlniu ttgrtnns, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b) to be ineffective against these two microorganisms [2, 3], See [1] Hervey, 1947; [2] Robbins et al„ 1945; [3] Wilkins, 1946b. Lcntlnus tigrtnas (?), a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Lentlniu vfllosa, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Lenzttes sp., a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Lenzttes abietina, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947a. Lenzttes betulina, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1,2,3]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [4]. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1946b; [4] Wilkins and Harris, 1944d. Lenzttes bkrolor, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1]. The culture media of this fungus are weakly inhibitory for Staph, aureus a n d / o r E. coli [2], See [1] Hervey, 1947; [2] Wilkins, 1947a. Lenzttes flacclda, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], See [1] Hervey, 1947; [2] Wilkins, 1947a. Lenzttes repanda, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], See [1] Hervey, 1947; [2] Wilkins, 1947a. Lenzttes saeplarta, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2] and b) to inhibit Staph, aureus and/or E. coli [3].

The culture media of this fungus are strongly inhibitory for Staph, aureus and/or E. coli [4J. Extracts of the sporophores are ineffective against these microorganisms [5]. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1946b; [4] Wilkins, 1947a; [5] Wilkins, 1946a. Lenzttes striata, a fungus which is effective in vitro against Staphylococcus aureus and/or Escherichia coli. See Wilkins, 1946b. Lenzttes thermophila, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. The culture media of this fungus are strongly inhibitory for Staph, aureus and/or E. coli [2], The fungus is also reported to be weakly inhibitory for Staph, aureus and/or E. coli [3]. See [1] Hervey, 1947; [2] Wilkins, 1947a; [3] Wilkins, 1947b. Lenzites trabea, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3], See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1948. Lenzites tricolor, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], See [1] Hervey, 1947; [2] Wilkins, 1946b. Leonotis leonuros, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Leontodon autnmnalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Leontodon hirtus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Leontodon hispidus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Leontopodium alpinum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Leonurus cardiaca, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [2], and in vivo against experimental malaria [3]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [4], See [1] Osborn, 1943; [2] Gottshall et al., 1949; [3] Spencer et al., 1947; [4] Hayes, 1947. Leonurus sibiricus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and in vivo against experimental malaria [2], See [1] Osborn, 1943; [2] Spencer et al., 1947. Leotia lubrica, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Lepachys pinnata, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Lepidagthls alopecuroidea, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947.

Cross references are indicated by

S M A L L CAPITALS

[161] Lepidium campestre, a higher plant, extracts of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus [1], In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Envinia carotovora, and Phytomonas tumefaciens [2], See [1] Carlson, Douglas, and Robertson, 1948; [2] Hayes, 1947. LepkUnm draba, a higher plant, the entire plant of which in vitro inhibits Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Lepidium hyssopifollum, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi [1, 2]. See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Lepidium lattfolhun, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lepidium sativum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. As test organism in vitro, see

YEASTS.

Lepidium virginicum, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Lepiota acutesquamosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota alba, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota amianthina, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota brunneo-incartiata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota bucknallii, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota carcharlas, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota castanea, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota clypeolaria, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota constricta, a fungus, extracts of the sporophores of which are ineffective in vitro

LEPIOTA NAUCINA

against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Lepiota cortinarhis, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota crista ta, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Pseudomonas aeruginosa [2], Sc« [1] Mathieson, 1946; [2] Wilkins and Harris, 1944d. Lepiota ermines, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Lepiota escoriata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota felina, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota fulvella, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota gracilenta, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores of this fungus are also ineffective against these two microorganisms [2], See [1] Wilkins, 1947c; [2] Mathieson, 1946. Lepiota granulosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota haemorrhaglca, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Lepiota Irrorata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota lenticularis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota lutea, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Lepiota mastoid ea, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepiota naucina, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2]. The culture media of this fungus are reported a) to be weakly inhibitory for Staph, aureus a n d / o r E. coli [3] and b ) to inhibit Staph, aureus in dilutions of 1:64 [1]. Extracts of the sporophores inhibit E. coli but not Staph, aureus and Pseudonomas aeruginosa [4], See [1] Robbins et al., 1945; [2]

Cross references are indicated by SMALL CAPITALS

LEPIOTA NAUCINA

[1621

Hervey, 1947; [3] Wilkins, 1947c; [4] Wilkins and Harris, 1944d. Lepiota naocina v. leucothltes, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Lepiota procera, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2]. See [1] Wilkins, 1947c; [2] Wilkins and Harris, 1944d. Lepiota rhacodes, a fungus, extracts of the sporophores of which are reported a) to be ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and b) to inhibit E. coli but not Staph, aureus and Pseudomonas aeruginosa [2]. The culture liquid and mycelial disks of this fungus are ineffective against Staph, aureus and E. coli [2]. See [1] Mathieson, 1946; [2] Wilkins and Harris, 1944d. Lepiota sistrata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Lepra sp., a lichen, extracts of which are effective in vitro against Staphylococcus aureus a n d / o r Bacillus subtilis. See Burkholder and Evans, 1945. Lepra sp. (?), a lichen, extracts of which are effective in vitro against Bacillus subtilis but not against Staphylococcus aureus and Escherichia coli. See Burkholder et al., 1944. leprosy, clinical, see CENTELLA ASIATICA.

Leptamnhim virginianum, a higher plant, aqueous extracts of which are effective in vitro against the spores of Neurospora crassa and ineffective against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Leptilon canadense, a higher plant, extracts of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus. See Carlson, Douglas, and Robertson, 1948. Leptoghim sp., a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Burkholder, Evans, et al., 1944. Leptonia asprella, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Leptonia formosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Leptonia fusca, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Leptonia lampropus, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Leptonia sarclta, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d.

Leptonia serkella, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Leptonia sernilata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Leptonia solstitialls, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Leptopodia elastic a, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Leptospermum laevigatum, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi [1, 2]. See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Leptospermum scoparium, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Leptosphaeria herpotrichoides, a fungus which in vitro inhibits Ophiobolus graminis. See Broadfoot, 1943a and b; Sanford and Broadfoot, 1931. Leptospira canicola, as test organism in

vitro,

s e e K O J I C ACID.

Leptospira icterohemorrhagiae. 1 As test organi s m in vitro,

s e e GRAMICIDIN; P E N I C I L L I N ; TYRO-

CIDINE. 2 E x p e r i m e n t a l i n f e c t i o n s , see AUREOM Y C I N ; K O J I C ACID; PENICILLIN,

leptospirosis, clinical, see AUREOMYCIN. Leptosyne douglasli, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Leptosyne stiilmanii, a higher plant, aqueous extracts of the leaf and stem of which are effective in vitro against Staphylococcus aureus, while aqueous extracts of the seedling, root, and flower, and ether extracts of the flower and leaf are ineffective. Only aqueous extracts of the flower and leaf inhibit Escherichia coli, and only aqueous and ether extracts of the flower inhibit the spores of Neurospora crassa. See Schnell and Thayer, 1949. Leptotaenia dissecta, a higher plant of the parsnip (Umbelliferae) family, from the root of which one cr more antibiotic substances are extracted. Steam distillation of the macerated roots yields two active oil fractions, one (A) colorless, the other (B) yellow. Both are bacteriostatic and bactericidal for gram-positive organisms. SPECTR UM.—Both oils inhibit the following microorganisms in vitro: Achromobacter lacticum Agrobacterium sp. Aspergillus niger Aspergillus terreus Bacillus circulans Bacillus megatherium Bacillus subtilis Candida albicans Corynebacterium diphtheriae Diplococcus pneumoniae Escherichia coli Fusarium sp. Fusarium culmorum

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

I I C A M A RIGIDA

[163] Microsporum trichoderma Mucor syl vatic us "Mucosus capsulatus" Mycobacterium phlei Mycobacterium smegma Mycoderma sp. Mycoderma lactis Pénicillium sp. Pénicillium cyclopium Pestallozia funera Pseudomonas fluorescens Pythium debaryanum Rhizoctonia oryzae Rhizoctonia solani Salmonella typhi Shigella paradysenteriae Shigella sonnei Staphylococcus aureus Streptococcus fecalis Streptococcus viridans Trichophyton sp. Zoogleal sp. Substance A inhibits the following organisms, while substance B is ineffective: Proteus sp. Proteus vulgaris Pseudomonas aeruginosa Serratia marcescens Shigella dysenteriae Substance A is also effective against the following organisms (B not tested): Clostridium botulinum Clostridium histolyticum Clostridium perjringens Clostridium putrificum Clostridium sporogenes Coccidioides immitis Hemophilus influenzae Histoplasma capsulatum Micrococcus tetragenus Mycobacterium tuberculosis Neisseria gonorrhoeae Neisseria intracellularis Streptococcus pyogenes Trichophyton sulphureum Substance B also inhibits Streptomyces griseus; substance A has not been tested against this organism. TOXICITY —Oil A diluted 1:100 in mineral oil and injected i.p. in 0.25-0.5 cc amounts in mice causes a staggering gait for a brief period, but the animals survive. Intraperitoneal injs of 0.25 cc of a 1:3 dilution are fatal. See Carlson and Douglas, 1948b. Leptotaenia multifeda, a higher plant, from the root of which an antibiotic substance is extracted. The macerated root is extracted with ethyl acetate, the extract evaporated, and the resulting oil washed with water. Purification is effected by washing the crude oil with sodium bicarbonate solution and water, dissolving in absolute alcohol, and adding an alcoholic solution of sodium bisulphite, followed by filtration, washing the precipitate with alcohol, and adding a mixture of acetic acid and petroleum ether. The ether layer is then washed with water, dried over sodium sulphate, and evaporated under reduced pressure. The resulting oil is dissolved in benzene, passed through a column p a c k e d with Magnesol-Celite, and eluted with a 200:1 benzene-ethanol mixture. Evaporation of the solvent yields a viscous oil the activity of which is somewhat reduced when subjected to 100°C. for 1 hr.

The active substance is ineffective in vitro against Aerobacter aerogenes, Klebsiella pneumoniae, and Salmonella schottmuelleri. It inhibits the following in vitro: Bacillus subtilis Corynebacterium diptheriae Diplococcus pneumoniae Escherichia coli Micrococcus aureus Mycobacterium lacticolor Mycobacterium phlei Mycobacterium tuberculosis hominis Neisseria catarrhalis Proteus vulgaris Pseudomonas aeruginosa Serratia marcescens Streptococcus pyogenes Vibrio comma Mice survive s.c injs of as much as 2.5% of total body wt. of the bisulphite purified preparations without any noticeable change in behavior. See Matson et al., 1949. Lespedeza capitata, a higher plant, aqueous extracts of the seed of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Leucanthemum gayanum subsp. demnatense, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. d-leucine, an amino acid which retards the growth of a strain of Lactobacillus arabinosus that requires 1-leucine. See Fox et al., 1944. Leucojum Vernum, a higher plant, aqueous extracts of the leaf, root, and bulb of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Leuconostoc sp., as test organism in vitro, see ASPERGILLIC ACID; B E R B E R I N E ; CHE1ROLINE; C L A V A C I N ; GLIOTOXIN; M Y C O P H E N O L I C ACID; PENICILLIC ACID; PROACTINOMYCIN; SPIRAEA; TYROTHRICIN.

Leuconostoc cftrovorus, as test organism vitro,

see BACILLUS sp.

vitro,

see

in

Leuconostoc mesenterioides, as test organism in BACILLUS VULGATUS.

leukemia, clinical, see AUREOMYCIN. Levisticum officinale, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Lewisia cotyledon, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lewisia tweedyi, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Leycesteria formosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Liatris pycnostachya, a higher plant, aqueous extracts of the seed and seedling of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Licania rigida, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Cross r e f e r e n c e s are indicated by SMALL CAPITALS

LICHENIFORMIN

II«]

tkhcalfomliK, an antibiotic substance produced by Bacillus licheniformis. It is isolated from the whole culture by repeated adsorption on charcoal and elution with acidified aqueous n-butanol, followed by conversion to the picrate, and finally conversion to the hydrochloride, a solid white material. Licheniformin hydrochloride is stable to autoclaving for 10 min at pH 1-9; however, 75% of its activity is lost on standing at rm. temp, at pH 7 in the light for 6 mo. The dry preparation withstands storage in the light at rm. temp. The hydrochloride is soluble in water, methanol, and ethanol, and insoluble in dry n-butanol, acetone, and nonpolar organic solvents. It does not melt but chars on strong heating. The activity is unaffected by the presence of serum. The size of the inoculum of test organisms has a definite effect on the end point. Mycobacterium phlei is the standard test organism, one unit being the equivalent in potency of 0.2 micrograms of a standard preparation. SPECTRUM.—A preparation of licheniformin assaying 2.5-5 million units per gm inhibits the following organisms in vitro: Inhibitory Organism concentration Actinobacillus lignieresi l:less than 10,000 Bacillus anthracis 1:200,000 Brucella abortus 1:320,000 Corynebacterium 1:1,250,000 — diphtheriae 1:10,000,000 Corynebacterium equi 1:5,000,000 Corynebacterium ovis low activity Corynebacterium pyogenes low activity Corynebacterium renale 1:40,000,000 Diplococcus pneumoniae\: 160,000—1:20,000 Erysipelothrix rhusiopathiae l:less than 5,000 Escherichia coli 1:80,000—1:10,000 Mycobacterium phlei 1:5,000,000— 1:2,500,000 Mycobacterium 1:640,000— tuberculosis 1:160,000 Pasteurella septica 1:640,000— l:less than 5,000 Pseudomonas aeruginosa 1:40,000 Salmonella schottmuelleri 1:20,000—1:10,000 Shigella dysenteriae 1:160,000—1:40,000 Staphylococcus 1: 5,000,000— pyogenes 1:1,250,000 Streptococcus spp. 1:1,250,000— 1:80,000 Streptococcus viridans 1:20,000 Vibrio cholerae 1:20,000 TOXICITY —The LDso for 18-20 gm mice is 5 mg i.v., 7.5 mg i.p., and 10 mg s.c.; the LDo values are 2.5 mg i.v., 2.5 mg i.p., and 5 mg s.c. Eighty-five percent of mice survive s.c. mis of 6 mg per day in two daily doses for 5-6 wks, but survivors are in poor condition and show glomerular-tubular damage in the kidneys. In cats 1-2 mg/kg causes a transient, sharp fall in b.p.; 10-20 mg/kg doses result in a shocklike condition. Licheniformin is not hemolytic, but it delays coagulation of the blood. ABSORPTION.—After s.c. inj in mice, the activity is present in the blood in detectable amounts.

EXPERIMENTAL CLINICAL RESULTS.— Total s.c. doses of 3.5-35 mg over a period of 3 days prolong life but do not prevent death in mice with Staph, pyogenes infections. A total of 18 mg s.c. in 3 days is somewhat more efficacious in Strep, pyogenes infections. In B. anthracis infections 3 s.c. injs of 3 mg each in one day prevent death in 84% of mice [1], The agent is of little value in the treatment of Coryne. diphtheriae infections in mice [2]. It is effective in reducing the severity of lung damage in mice with experimental tuberculosis, but the most effective dosage is also nephrotoxic [1]. See [1] Callow et al., 1947; [2] Hewitt, 1948. llchesteric acid, an antibiotic produced by several lichens. It inhibits staphylococci in vitro. See Castle and Kubsch, 1949. Lignstnim ionandrhim, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Ligustnim nepalense, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Ligustrum vulgare, a higher plant, aqueous extracts of the seed of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other aqueous extracts of this plant inhibit Staph, aureus but not E. coli [2], See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Ligustrum walkerl, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Lilium aura tum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Lilium candldum, a higher plant, aqueous extracts of the bulb, flower, leaf, and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other aqueous extracts of this plant are also ineffective against Staph, aureus and E. coli [2]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943. Lilium longifolium, a higher plant, aqueous extracts of the bulb, leaf, and stem of which are effective in vitro against Escherichia coli. Only aqueous extracts of the bulb inhibit the spores of Neurospora crassa, and none of these extracts inhibits Staphylococcus aureus. See Schnell and Thayer, 1949. Lilium martagon, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Ösbom, 1943. Lilhim regale, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Liihim speciosum, a higher plant, aqueous extracts of the flower, leaf, and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and spores of Neurospora crassa. See Schnell and Thayer, 1949. Llmnanthemum aquaticum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Limnanthemnm humboldtianum, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947.

C r o s s r e f e r e n c e s a r e indicated by SMALL CAPITALS

[165] Llmonhim sinuatum, a higher plant, aqueous extracts of the seed and entire plant of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Linaria alpina, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Linaria bipartite, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Linaria cymbalaria, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Linaria linaria, a higher plant, aqueous extracts of the leaf and aqueous and etner extracts of the flower of which are effective in vitro against Staphylococcus aureus, while ether extracts of the leaf and aqueous and ether extracts of the stem and root are ineffective. None of these extracts inhibits Escherichia coli and the spores of Neurospora crassa [1]. Other extracts of this plant inhibit Staph, aureus and E. coli [2]. See [1] Schnell and Thayer, 1949; [2] Carlson, Douglas, and Robertson, 1948. Linaria marocanna, a higher plant, aqueous extracts of the seed, flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Linaria vulgaris, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Llndenbergia grandiflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Llndera benzoin, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Lindere sericea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Llndera strychnifoiia, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. linolcic acid, a naturally occurring acid with a wide distribution. It has been shown to be the antibiotic principle found in the mycelia of Penicillium crustosum. Linoleic acid is effective in vitro against Mycobacterium phlei, Myco. tuberculosis avium, and Myco, tuberculosis hominis but not against Staphylococcus aureus. See Riley and Miller, 1948. Linum aipinum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Linum arboreum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Linum catharticum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

LISTERA OVATA

Linum cbamissonis, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al, 1947. Linum flavum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Linnm narbonense, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Linum pe renne, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Linum usttatissimum, a higher plant, aqueous extracts of the seed, seedling, flower, leaf, and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Lippia citriodora, a higher plant, aqueous extracts of the seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other extracts of this plant are also ineffective against Staph, aureus, E. coli, and Mycobacterium tuberculosis [2]. See [1] Schnell and Thayer, 1949; [2] Gottshall et al., 1949. Lippia graveolens, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Lippia lanceolata, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Liquldambar styraciflua, a higher plant, aqueous extracts of the fruit, leaf, and stem of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Liriodendron tulipifera, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli [1]. Extracts of the bark of this plant are slightly effective in the treatment of experimental malaria [2], In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staphylococcus aureus, E. coli, Envinia carotovora, and Phyto mo nas tumefaciens [3], See [1] Sanders et al., 1945; [2] Spencer et al., 1947; [3] Hayes, 1947. Liriope graminifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Liriope muscari, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Liriope spicata v. glabra, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lisianthus sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Lissan al thaur, common name of a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Listera ovata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Cross references are indicated by SMALL CAPITALS

LISTERELLA MONOCYTOGENES Listcrcila monocytogenes, as test organism in vitro,

see CHAETOMIN.

Lithospennum arvense, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumejaciens. See Hayes, 1947. Lithospennum canescens, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumejaciens. See Hayes, 1947. Lithospennum intermedium, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lfthospermum officinale, a higher plant, concentrated aqueous extracts of the Chinese drug prepared from the root of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Gaw and Wang, 1949. Lithospennum prostratum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lithospennum purpurea-caeruleum, a h i g h e r plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lithraea moiieoides, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. litmocidin, an antibiotic pigment produced by Proactinomyces (formerly Actinococcus) cyaneus-antibioticus [1]. The pigment is extracted from the culture medium with water [2], The water extract is acidified, precipitating an inactive protein with the active pigment. The protein and pigment are separated by repeated solution and precipitation, which results in an aqueous solution of the pigment. The active principle is obtained by adsorption from the water extract on charcoal, acidification, elution with acid acetone, and reprecipitation [2], Litmocidin is red when acid, blue when alkaline, and violet when neutral [1,2]. The acid form is soluble in water, ethanol, and acetone, and is stable to boiling in the acid range for 30 min. The m.p. is 144M46°C. (decomp.) [2]. The activity of this substance is unaffected by 10-30% human or horse serum. It is bactericidal as well as bacteriostatic for some microorganisms. "The unit of activity of litmocidin is that quantity of the substance which is just sufficient to inhibit completely the growth of Staph, aureus in one ml. of broth" [1], SPECTRUM.—Litmocidin is very strongly inhibitory for Mycobacterium tuberculosis. It inhibits the following in vitro at dilutions of 1:500,000 to 1:4,000,000 [1]: Staphylococcus aureus Streptococcus hemolyticus Streptococcus viridans Vibrio comma Escherichia coli, Salmonella paratyphi, Saint, schottmuelleri, Salm. typhi, and Shigella dysenteriae are inhibited by 1:1,000 to 1:10,000 [1].

TOXICITY.—Twenty-gram mice survive i.p. injs of 3,000 units; 4,000-5,000 units i.p. causes 50% mortality; 100% are killed by 10,000 units [1]. EXPERIMENTAL CLINICAL RESULTS — Subcutaneous injs of 50-500 units, one to three times a day for 3 days in mice infected with Staph, aureus, have no chemotherapeutic effect [1], See [1] Gause, 1946b; [2] Brazhnikova, 1946. Litsea japonka, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Litsea zeylanica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Loasa parviflora, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. lobar pneumonia, clinical, see AUREOMYCIN. Lobaria pulmonaria, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Lobelia cardinalis, a higher plant, aqueous and ether extracts of the flower, leaf, and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Lobelia erinus compacta, a higher plant, aqueous extracts of the seed of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Lobelia syphilitica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lobularia maritima, a higher plant, aqueous extracts of the seed, seedling, flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Loeselia mexicana, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Lolium perenne, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lomatia ferruginea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lomatia silaifolia, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi [1,2], See [1] Atkinson and Rainsford, 1946: [2] Atkinson, 1949. Lonchocarpus bockii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lonchocarpus sericeus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lonicera alpigena, a higher plant, aqueous extracts of which are ineffective in vitro against

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[167] Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lonicera bracteata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lonicera henryl, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lonicera japonica, a higher plant, concentrated extracts of the Chinese drug prepared from the vine of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Aqueous and ether extracts of the berry and stem of this plant are also ineffective against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [2], See [1] Gaw and Wang, 1949; [2] Schnell and Thayer, 1949. Lonicera ledebourii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lonicera periclymenum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lonicera sempervirens, a higher plant (trumpet honeysuckle), aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Lonicera tatarica, a higher plant from which two antibiotic principles have been obtained. Principle A is effective in vitro against Staphylococcus aureus, Escherichia coli, Phytomonas campestris, and Ph. phaseoli. It is extractable from the plant with water, methanol, and ethanol. It is slightly soluble in ethyl acetate, nearly insoluble in chloroform, and insoluble in ethyl ether, petroleum ether, toluene, and carbon tetrachloride. Its activity is destroyed by boiling for several hours. Principle B inhibits E. coli, Phytomonas campestris, and Ph. phaseoli, but not Staph, aureus. It is extractable with water, methanol, ethanol, and dioxane. It is similar to principle A in solubility and stability [1]. Another extract of this plant is reported to inhibit E. coli but not Staph, aureus and Mycobacterium tuberculosis [2], See [1] Lucas and Lewis, 1944; [2] Gottshall et al., 1949. Lonicera tellmanniana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lopezia miniata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Loureira cochinchinensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Luculia pinceana, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Lucuma caimito, a higher plant, extracts of which are reported to be ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948.

LUPULON A N D HUMULON

Lucuma mammosa, a higher plant (marmalade fruit or mammee sapota), aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lucuma saiicifoiia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Ludwigia aiternifolia, a higher plant (seedbox or rattlebox), extracts of which are reported to be effective in vitro against Escherichia coli but not against Bacillus subtilis. See Sanders et al., 1945. Lunaria annua, a higher plant (honesty, moonwort, or satinflower), aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lunaria biennis, a higher plant, aqueous and ether extracts of the leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Lunaria rediviva, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. lung abscess, clinical, see AUREOMYCIN. Lupinus arboreus, a higher plant (tree lupine), aqueous extracts of which are reported to be ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lupinus polyphyllus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Lupinus pubescens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. lupuion and bumulon, two crystalline antibiotic agents extracted from the strobiles of the hops plant, Humulus lupulus. Lupuion is isolated by extracting the dried and ground hops with petroleum ether, concentrating the extract in vacuo, crystallizing by refrigeration, and recrystallizing from petroleum ether and aqueous methanol. The o-phenylenediamine salt of humulon is obtained by diluting the mother liquor from the lupuion crystals with petroleum ether, heating to 40°C., adding o-phenylenediamine in boiling benzene, crystallizing by refrigeration, and washing the crystals with cold benzene and petroleum ether. The free substance is obtained by converting to the lead salt and treating with sulphuric acid. Both substances are fairly soluble in organic solvents such as methanol, ethanol, petroleum ether, hexane, and iso-octane, and slightly soluble in neutral or acidic water. Lupuion is moderately stable to acid and alkali but is inactivated at rm. temp, when exposed to air [1]. Sodium chloride and serum decrease its activity [2], Humulon is relatively stable to acid. The presence of ascorbic acid protects the bacteriostatic property of both agents [1]. Lupuion has the formula C26H3SO4 and melts at 92°C. It is optically inactive. Humulon, C21H30O5, is optically active and melts at 55°C. [1]. Lupuion may exist in any of the forms indicated by the three following structural formulas; it may be noted that forms B and C probably predominate [3].

Cross references are indicated by SMALL CAPITALS

LUPULON AND HUMULON

[ 168]

Formula A

O H C

11

n

^

V

(CH»)i — C = CH — CHJ — C

C — C — CH2 — CH(CHi)»

X

0 = 1

C — OH

S

(CHs)i — C H — C H = CH

Formula B

fcH = CH —CH(CHJ)»

H 0

yC C — IIC°— C H j — C H ( C H s ) j

I I

/i ml of physiological saline solution s.c. o n the back of the neck; whereas group 2 received 4. The active substance is neutral; its antibiotic properties are destroyed by cold alkali [1]. SPECTRUM—Escherichia coli, Pioteus i ulgaris, and Staphylococcus aureus arc inhibited in vitro at 1:4,000; Pseudomonas aeruginosa is unaffected by 1:2,000 [1]. Aqueous extracts are also reported to inhibit Staph, aureus and E. coli [2], See [1] Abraham, Heatley, Rolt, and Osbom, 1946; 12] Osborn, 1943. Spiraea bullata, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Spiraea bumalda, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Spiraea japonka v. alba, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Spiraea latifolia, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Spiraea lindleyana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Spiraea sorbifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Spiraea thunbergli, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Spiraea tomentosa, a higher plant, various extracts of which are effective in vitro against Escherichia coli [1, 2] but not against Staphylococcus aureus [1] and Bacillus subtilis r—1 Other extracts of this plant are ineffee ive against experimental malaria [31. See [1] Carlson, Douglas, and Robertson, 1948; [2] Sanders et al., 1945; [3] Spencer et al„ 1947. Spirillum, as test organism in vitro, see T R Y P ANOTOXIN.

Spirillum duttoni, as test organism in vitro, see CORYLOPHYLINE.

Spirillum minus, experimental

infections, see

PENICILLIN.

Spirillum rubrum, as test organism in vitro, see KOJIC

ACID.

Spirochaeta vitro,

gallinarum, as test

s e e A N A C A R D I C ACID.

organism

in

spleen. Human and beef spleen contain a factor which is germicidal for Streptococcus hemolyticus [1] and Strep, pyogenes [2], Sublethal concentrations cause changes in the morphological and biochemical characteristics of Strep.

pyogenes. Spleen extract first depresses, then stimulates the growth of Staphylococcus aureus. Pneumococci are unaffected by the extract, but Mycobacterium tuberculosis is inhibited. The colon-typhoid dysentery bacteria show increased growth and morphological changes [2], See 111 Nutini and Kreke, 1942; [2] Nutini et al.. 1945. Spondias axillaris, a higher plant, aqueous extracts of which are ineffective in \itro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Spondias magifera, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Sporobolomyces roseus, as test organism in vitro, see M Y C O S U B T I L I N . Sporobolomyces salmonicolor, as test organism in vitro, see A C T I D I O N E . Sporodinia grandis, a fungus, the culture medium of which is ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1943a. Sporotrichum spp., as test organism in vitro, see

EUMYCIN.

Sporotrichum globulum, a fungus which gives doubtful results when tested in vitro against Staphylococcus aureus and Escherichia coli. See Riobbins et al., 1945. Sporotrichum schenckii, as test organism in vitro, see A C T I D I O N E ; A N T I B I O T I C 136; A N T I B I OTIC XG: BACILLOMYCIN; POI.YPEPriN; SUBTILIN.

CHLORAMPHENICOL;

Sprekelia formosissima, a higher plant, extracts of the bulbs of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Spyridium globulosum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Stacbybotrys atra, a fungus which is effective in vitro against Salmonella typhi and Endomycopsis albicans but not against Staphylococcus aureus. The culture media of this fungus inhibit Botrytis allii but not Staph, aureus. See Brian and Hemming, 1947. As test organism in vitro, see T R I C H O T H E C I N . Stachys betonica, a higher plant, aqueous extracts of which are ineffective in \itro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Siachys hirta, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Stachys longifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Stachys sylvatica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Stachyurus chinensis. a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Staphylea colchica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Cross references are indicated by

SMALL

CAPITALS

I 275 ] staphylococcal infections. 1 Clinical, see AUREOMYCIN; BACIIRACIN; CITRININ; P E M C I L I .IN; STREPTOMYCIN. 2 E x p e r i m e n t a l , s e e CORYLOPHYLINE; PENICMUN.

staphylococcal subacute bacterial endocarditis, clinical, see S I R E P I O M Y C I N . staphylococcal urinary infections, clinical, sec AUREOMYC1N.

Staphylococcus, a group of microorganisms which produces at least one antibiotic. A. A thermostable substance extracted f r o m the culture filtrate by treatment with fuller's earth and anhydrous acetone. It is stable at p H 2-8, soluble in acetone, methanol, and ethanol, and insoluble in benzene, chloroform, and butanol. The activity is destroyed by reducing compounds but unaffected by reaction with various metallic ions. Associated with the active principle is a toxic substance; separation has not yet been achieved [I]. B. Of 205 strains of staphylococci tested, 26 strains, including 6 of Staph, albas, were effective in streak tests against Staph, aureus, Corynebacterium xerosis, Coryne. diphtheriae gravis, Coryne. diphtheriae mitis, Coryne. diphtheriae intermedins, and Coryne. hoffmannii, and ineffective against Escherichia coli, Pseudomonas aenmiiursa. and Salmonella enteritidis. The activity is not due to the production of hydrogen peroxide [21. Sec [11 Magrassi and Spiga, 1946; [21 Jennings and Sharp, 1947. Staphylococcus spp., as lest organisms in vitro, see ANTISMEGMATIS FACTOR; ASPERGILLUS Spp.; BACILLIN; BACITRACIN; CLITOCYBINES; CORYLOPHYLINE; E U M Y C I N ; C.LJOTOXIN; INSECTICIN; L I C H E S T E R I C ACID; M I C R O C O C C I N ; M O L D , RED, U N IDENTIFIED; POLYMYXINS; PROSOPIS JULIFLORA; PSEUDOMONAS AERUGINOSA; STREPTIN; USTIN.

Staphylococcus albus, as test organism in

vitro,

s e e ANTIBIOTIC 1 3 6 ; A R C T I U M M I N U S AND O N O PORDON T A U R I C U M ; A S A R U M CANADENSE v . REF L E X U M ; AUREOMYCIN; AYFIVIN; BACILLIN; BACILLUS LARVAE; BIOCERIN; BLOOD; CIRCULIN; CITRININ; C O P T I S CHINENSIS; ESCHERICHIA COLI; FUMIGACIN; FUSCIN; GEODIN; GLIOTOXIN; HERQ U E I N ; K O J I C ACID; M I C R O C O C C I N ; MYCELIANAMIDE; MYCETIN; NIDULINE; NOTALYSIN; PENICILLIN; PERSOONIA PINIFOLIUS; PROTOANEMON I N ; PSALLIOTA XANTHODERMA; PSEUDOMONAS FLUORESCENS; PSEUDOMONAS PUTIDA; QUERCETIN; STREPTOMYCIN; STREPTOTHRIX; SUBTENOLIN; T E R R A M Y C I N ; T H U J A PLICATA; X A N T H O M Y -

CINS A AND B. For literature see Burkholder and Evans, 1945 (lichens). Staphylococcus aureus, a microorganism, one strain of which produces an antibiotic substance. It is isolated by evaporating the culture fluid, precipitating the active fraction with hydrochloric acid, dissolving the precipitate in water, and reprecipitating with trichloracetic acid. The active principle is thermostable in the neutral and acid p H range. Above pH 9, the activity is destroyed at rm. temp. The agent is also destroyed by trypsin and pepsin.

SPECTRUM. — Bacillus antliracis, Corynehacterium xerosis, Staphylococcus aureus, and Streptococcus pyogenes are completely inhibited in vitro by dilutions of 1:1,500-1:6,000. Coryne. diphtheriae gravis is partially inhibited at 1:770. The substance is also active against Micrococcus lysodeikticus and Mycobacterium phlei and inactive against Coryne. diphtheriae irvermedius, Escherichia coli, Myco. smegma,

STAPHYLOCOCCI'S A l R E I S

Pseudomonas aeruginosa. Salmonella enterilidis, and Shigella sonnei [1], It is also reported that various strains of Staph, aureus are effective in vitro against Jrichophyton schoenleini. The activity is not f o u n d in extracts, culture filtrates, or in culture media sterilized by heat [2[. In another series of tests in vitro Staph, aureus is reported effective against Actinomyces violaceus and A. aurantiacus, and ineffective against A. gri.seus and A. globisporus [3]. See [1] G a r d n e r , 1949; [2J Vanbreuseghem, 1948; [3] Krassilnikov and Koreniako, 1939. 1 As test organism in vitro, see ABSIDIA GLAUCA; A C A N T I I O P Y R U S s p . ; A C H I L L E A MILLEFOLIUM; ACORUS CALAMUS; ACTIDIONE; ACTINOMYCIN; ACTINORUBIN; ADIANTUM PEDATUM; AESCULUS HIPPOCASTANUM; AGRIMONIA s p . ; A G R O S T E M M A GITHAGO; A L E U R I S M A LUGDUNENSE; ALLICIN; A L L I U M CEPA; A L L I U M C E R N U M ; A L L I U M SATIVUM; A L L I U M SCHOENOPRASUM; A L L I U M TRICOCCUM; ALLIUM VINEALE; ALVEIN; AMBROSIA ARTEMISIIFOLIA; AMBROSIA TRIFIDA; A N E M O N E CANADENSIS; A N E M O N I N ; A N T E N N A R I A PARLINII; A N T E N N A R I A PLANTAGINIFOLIA; ANTIBIOTIC 136; ANTIBIOTIC 3 5 1 0 ; ANTIBIOTIC H - 3 ; ANTIBIOTIC " V " ; ANTIBIOTIC X G ; APOCYNUM CANNABINUM; ARABIS HIRSUTA; ARALIA SPINOSA; A R C T I U M M I N U S AND ONOPORDON TAURICUM; ARISAEMA TRIPHYLLUM; A R U N C U S SYLVESTER; A S A R U M CANADENSE; A S A R U M CANADENSE v. R E F L E X U M ; ASCLEPIAS SYRIACA; A S C L E P I O D O R A V I R I D I S ; A S I M I N A T R I L O B A ; A S P A R A G U S O F F I C I N A L I S ; A S P E R G I L L I C A C I D ; ASPERGILLIN; ASPERGILLUS s p . ; ASPERGILLUS s p p . ; ASPERGILLUS AMSTELODAMI; ASPERGILLUS CANDIDUS; A S P E R G I L L U S CARBONARIUS; A S P E R G I L L U S CINNAMOMEUS; ASPERGILLUS CITRISPORUS; A S PERGILLUS CLAVATUS; A S P E R G I L L U S D I S J U N C T U S ; ASPERGILLUS EFFUSUS; ASPERGILLUS FICUUM; A S P E R G I L L U S FLAVUS; A S P E R G I L L U S F U M A R I C U S ; ASPERGILLUS FUMIGATUS; ASPERGILLUS FUSCUS; ASPERGILLUS GIGANTEUS; ASPERGILLUS GLAUCUS; ASPERGILLUS JAPONICUS; ASPERGILLUS JEANSELMEI; ASPERGILLUS LUCHUENSIS; ASPERGILLUS MALIGNUS; ASPERGILLUS MELLEUS; A S P E R GILLUS MOLLIS; ASPERGILLUS NIDULANS; ASPERGILLUS NICER; ASPERGILLUS NICER CITRICUS; ASPERGILLUS NOVUS; ASPERGILLUS OCHRACEUS; ASPERGILLUS ORYZAE; ASPERGILLUS PARASITICUS; ASPERGILLUS PROFUSUS; ASPERGILLUS RÉPANDUS; ASPERGILLUS REPENS; ASPERGILLUS RESTRICTUS; ASPERGILLUS SCHIEMANNI; ASPERGILLUS SULPHUREUS; ASPERGILLUS SYDOWI; ASPERGILLUS TAMARII; ASPERGILLUS TERREUS; ASPERGILLUS TERRICOLA; ASPERGILLUS USTUS; ASPERGILLUS VERRUCULOSUM; ASPERGILLUS VERSICOLOR; A S PERGILLUS VIOLACEOFUSCUS; ASPERGILLUS W E N T I I ; A S P I D I U M M A R G I N A L E ; A S T A S I A KLF.BSF.II; A U R E O M Y C I N ; A V E N A C E I N ; A Y F I V I N ; B A C I L I P I N A AND B ; BACILLIN; B A C I L L U S s p . ; B A C I L LUS ALVEI; B A C I L L U S BREVIS; B A C I L L U S CAROTARUM; BACILLUS CEREUS; BACILLUS CIRCULARES; BACILLUS COAGULANS; BACILLUS F I R M U S ; BACILLUS FUSIFORMIS; BACILLUS LARVAE; BACILLUS LATEROSPORUS; BACILLUS LICHENIFORMIS; BACILLUS MACERANS; BACILLUS M E G A T H E R I U M ; BACILLUS MYCOIDES; BACILLUS P U M U L I S ; BACILLUS SUBTILIS; B A C I L L U S V U L G A T U S ; BACILYSIN; BACITRACIN; BARBAREA VULGARIS; BASIDIOBOLUS RANARUM; BELAMCANDA CHINENSIS; BENZOIN AESTIVALE; BERBERIS THUNBERGII; BIFORMIN; B I F O R M I N I C ACID; B I O C E R I N ; B L E P H I L I A CILIATA;

Cross references are indicated by SMALL CAPITALS

STAPHYLOCOCCUS

AUREUS

[276]

BLOOD; BORRELIDIN; B O T R Y C H I U M VIRGINIANUM; BRASSICA NIGRA; BUCHLOE DACTYLOIDES; BUTCAPTERCUP; CAMPTOSORUS RHIZOPHYLLUS; SELLA BURSA-PASTORIS; CARDAMINE BULBOSA; CARDAMINE PENNSYLVANICA; CARDUUS CRISPUS; CAREX STRICTA; CARNEOLUTESCIN; CASTALIA TUBEROSA; CASTILLEJA COCCINEA; C A U L O P H Y L L U M THALICTROIDES; C E L A S T R U S SCANDENS; CENTAUREA MACULOSA; C E R A T O P H Y L L U M DEMERSUM; CHAEROPHYLLUM PROCUMBENS; CHAETOCLADIUM BREFELDU; CHAETOMIN; CHAET O M I U M C L A T U M ; CHARA FOETIDA; CHENOPODIUM ALBUM; C H I L O M O N A S PARAMECIUM; C H I MAPHILA MACULATA; CHLORAMPHENICOL; CHROMOBACTERIUM PRODIGIOSUM; CHRYSANT H E M U M L E U C A N T H E M U M ; C I B O T I U M SCHIEDEI; CICHORIUM INTYBUS; CICUTABULBIFERA; C I C L T A MACULATA; CIMICIFUGA RACEMOSA; CIRCULIN; C I R S I U M ARVENSE; C I T R I N I N ; CLADONIA RANGIFERINA; CLAVACIN; CLOSTRIDIUM AEROFEOETID U M ; CLOSTRIDIUM BIFERMENTANS; CLOSTRIDIUM B O T U L I N U M ; CLOSTRIDIUM BUTYRICUM; CLOSTRIDIUM CENTROSPOROGENES; CLOSTRIDIUM CHAUVOEI; CLOSTRIDIUM FALLAX; CLOSTRIDIUM FELSINEUS; CLOSTRIDIUM HISTOLYTICUM; CLOSTRIDIUM M U L T I F E R M E N T A N S T E N A L B U M ; CLOSTRIDIUM OEDEMATIENS; CLOSTRIDIUM PARASPOROGENES; CLOSTRIDIUM P U T R I F I C U M ; CLOSTRIDIUM SEPTICUM; CLOSTRIDIUM SORDELLII; CLOSTRIDIUM SPHENOIDES; C L O S T R I D I U M SPOROGENES; CLOSTRIDIUM T E R T I U M ; CLOSTRIDIUM TETANI; CLOSTRIDIUM T E T A N O M O R P H U M ; CLOSTRIDIUM WELCHII; COLISTATIN; CONOCEPHALUM CONICUM; C O N V O L V U L U S ARVENSIS; COPTIS CHINENSIS; CORTINARIUS ROTUNDISPORUS; CRATAEGUS sp.; CREPIN; CREPIS BIENNIS; CROCUS VERNUS; C T E N O M Y C E S ASTEROIDES; C U N I L A ORIGANOIDES; C U N N I N G H A M E L L A ECHINULATA; C U N N I N G H A M E L L A ELEGANS; CUSCUTA sp.; C Y N O GLOSSUM V I R G I N I A N U M ; C Y P E R U S PAPYRUS; CYSTOPTERIS FRAGILIS; D A C T Y L I S GLOMERATA; DATISCETIN; DAUCUS CAROTA; DECODON VERTICILLATUS; D E N T A R I A LACINIATA; DESTRUIN; DLANTHERA AMERICANA; DLCENTRA CANADENSIS; DICOUMARIN; DIOSPYROS VIRGINIANA; DIPLOCOCCIN; DIPSACUS SYLVESTRIS; DODECATHEON MEADIA; ELEUSINE INDICA; ENDOSUBTILYSIN; E N N I A T I N ; EPIDERMOPHYTON FLOCCOSUM; E P I PACTIS TESSELATA; E Q U I S E T U M ARVENSE; ERAGROSTIS CILIANENSIS; ERIGERON PHILADELPHICUS; ERYTHRONIUM AMERICANUM; EUGLENA GRACILIS; E U O N Y M U S OBOVATUS; EUPATORIUM PURPUREUM; EUPHORBIA COROLLATA; FREQUENTIC ACID; FOMES OFFICINALIS; FRADICIN; FRUCTIGENIN; FUMIGACIN; FUSCIN; GALINSOGA PARVIFLORA; G A L I U M APARINE; GAULTHERIA PROCUMBENS; GENTISYL ALCOHOL; GEODIN; GERANIUM MACULATUM; GEUM VERNUM; G I N K G O BILOBA; G I L L E N I A STIPULATA; GLADIOLIC ACID; GLIOTOXIN; G L U T I N O S I N ; GRAMICIDIN; GRAMICIDIN S; GRISEIN; H A N S E N U L A ANOMALA; HEART; HEDERA HELIX; HERACLEUM L A N A T U M ; HERQUEIN; HEUCHERA SANGUINEA; HEUCHERA VILLOSA; HIBISCUS MOSCHEUTOS; HIERACIUM VENOSUM; HIRSUTIC ACIDS; HOUSTONIA CAERULEA; HOUSTONIA LONGIFOLIA; H Y D R O P H Y L L U M APPENDICULATUM; H Y P E R I C U M PERFORATUM; ILEX DECIDUA; ILEX OPACA; I M P A T I E N S PALLIDA; I N U L A SPIRAEIFOLIA; IODANTHUS PINNATIFIDUS; IODININ; IPOMOEA BATATAS; IRIS GERMANICA; JAVANICIN; JUNIPERUS HORIZONTALIS; KOJIC ACID; KRIGIA AMPLEXICAULIS; LACHNEA CRETEA; LACTUCA CANADENSIS; L A M I U M PURPUREUM; LAPORTEA CANADENSIS; LATERITIINS; LATERO-

SPORIN A AND B ; LAVENDULIN; LEONURUS CARDIACA; LEPACHYS P I N N A T A ; L E P I D I U M CAMPESTRE; L E P I D I U M DRABA; L E P I D I U M VIRGINICUM; LEPTOTAENIA DISSECTA; LINOLEIC ACID; L I R I O DENDRON TULIPIFERA; L I T H O S P E R M U M ARVENSE; L I T H O S P E R M U M CANESCENS; LITMOCIDIN; L U P U LON AND H U M U L O N ; L Y C H N I S ALBA; LYCOPERSIC U M P I M P I N E L L I F O L I U M ; LYCOPODIUM LUCIDUL U M ; LYGODIUM JAPONICUM; LYSIMACHIA N U M M U L A R I A ; LYSIMACHIA QUADRIFOLLA; M A L V A ROTUNDIFOLIA; MARASMIUS ALLIACEUS; M A R A S MIUS ANDROSACEUS; M A R A S M I U S FOETIDUS; M A R A S M I U S G R A M I N U M ; MARASMIUS RAMEALIS; M A R A S M I U S ROTULA; MARASMIUS SCORODONIUS; MEDEOLA VIRGINIANA; M E D I C A G O L U P U L I N A ; MELILOTUS ALBA; MENYANTHES TRIFOLIATA; 2 - M E T H O X Y - I , 4-NAPHTHOQUINONE; 5 - M E T H O X Y P-TOLUQUINONE; MICROMONOSPORIN; MICROSPORUM AUDOUINI; M U S A S A P I E N T U M ; MUSARIN; MYCELIANAMIDE; M Y C E T I N ; MYCOPHENOLIC ACID; MYCOSUBTILIN; MYXOCOCCUS VIRESCENS; N E PETA H E D E R A C E A ; NEPHROLEPIS CARDIFOLIA; NEPHROLEPIS EXALTATA V. BOSTONIENSIS; NIDULINE; NOCARDIA GARDNERI; NOCARDIN; N O T A L Y SIN; N O T A T I N ; NUDIC ACID A AND B ; O E N O THERA BIENNIS; OENOTHERA FRUTICOSA; O N C O PELTUS FASCIATUS; ONOCLEA SENSIBILIS; O S MORHIZA CLAYTONI; OSMORHIZA LONGISTYLIS; O S M U N D A REGALIS; OXALIS STRICTA; PAEONIA OFFICINALIS; PANAX QUINQUEFOLIUM; PARASORBIC ACID; PASTINACA SATIVA; PEDICULARIS CANADENSIS; PENATIN; PENICILLIC ACID; PENIC I L L I N ; PENICILLIUM EXPANSUM ( ? ) ; P E N I C I L L I U M NIGRICANS-JANCZEWSKII SERIES; P É N I C I L L I U M RESFRICULOSUM, n. sp.; P E N T S T E M O N LAEVIGATA'S; PERSOONIA PINIFOLIUS; PHACELIA PURSHII; PHLOX DIVARICATA; PHOENICIN; PHTHIOCOL; PHYSOCARPUS OPULIFOLIUS; PICEA ABIES; PINOSYLVINE; P I N U S STROBUS; PLANTAGO LANCEOLATA; PLANTAGO MAJOR; P L A T A N U S OCCIDENT A L « ; PLEUROTIN; POA PRATENSIS; PODOPHYLL U M P E L T A T U M ; P O L E M O N I U M REPTANS; P O L Y GONATUM BIFLORUM; P O L Y G O N U M A M P H I B I U M ; P O L Y M Y X I N S ; POLYPEPTIN; P O L Y P O D I U M AUREU M ; P O L Y P O D I U M LONGIFOLIUM; P O L Y P O D I U M POLYPODIOIDES; P O L Y P O D I U M VULGARE; P O L Y PORIN; POLYSTICHUM ACROSTICHOIDES; POLYSTICHUM LONCHITIS; POTAMOGETON CRISPUS; POTAMOGETON NATANS; POTAMOGETON PECTINATUS; POTENTILLA CANADENSIS; POTENTILLA RECTA; PROACTINOMYCIN; PROSOPIS JULIFLORA; PROTAMINE ZINC INSULIN; PROTOANEMONIN ; PRUNELLA VULGARIS; PRUNUS PERSICA; PSALLIOTA XANTHODERMA; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS FLUORESCENS; PSEUDOMONAS PUTIDA; P S I L O T U M N U D U M ; PSORALEA PEDUNCULATA; PTERIS AQUILINA; PTERYGOSPERMIN; PUCHIIN; PUROTHIONIN; PYO COMPOUNDS; PYOC Y A N I N ; QUERCETIN; RAMEALIN; R A N U N C U L U S ABORTIVUS; RANUNCULUS OCCIDENTAL«; RANUNCULUS S E P T E N T R I O N A L « ; RAPHANIN; RHEIN; R H E U M RHAPONTICUM; RHUS CANADENSIS; R H U S HIRTA; RIBES VULGARE; RIPORIA LABRUSCA; R U E I L I A CILIOSA; R U M E X ACETOSELLA; R U M E X CRISPUS; SABOURAUDITES GALLINAE; SABOURAUDITES LANOSUS; SAGITTARIA LATIFOLIA; SALVIA LYRATA; SALVINIA NATANS; SAMBUCININ; S A M BUCUS CANADENSIS; SANGUINARIA CANADENSIS; SAPONARIA OFFICINALIS; SARRACENIA PURPUREA; SEDUM STOLONIFERUM; SELAGINELLA BRAUNII; SELAGINELLA KRAUSSIANA; SENECIO AUREUS; SERUM; SIDA HERMAPHRODITA; SILENE VIRGINICA; S I L P H I U M PERFOLIATUM; S I L P H I U M TEREBINTHINACEUM; SMILACINA RACEMOSA; S M I L A -

C r o s s r e f e r e n c e s a r e i n d i c a t e d b y SMALL CAPITALS

[277] C I Ñ A STELLATA; S O L A N I N E ; S O L A N U M CAROLIN E N S E ; S O L A N U M DULCAMARA; S P A R T I N A MIC H A U X I A N A ; SPECULARIA PERFOLIATA; S P I N U L O S I N ; SPIRAEA ARUNCUS; SPLEEN; STAPHYLOCOCCUS; STAPHYLOCOCCUS AUREUS; STELLARIA MEDIA; STERIGMATOCYSTIN; STREPTOMYCES ANTIBIOTIC U S ; S T R E P T O M Y C E S AURANTIACUS; S T R E P T O M Y C E S A U R E O F A C I E N S ; S T R E P T O M Y C E S GLOBIGISPOR U S ; S T R E P T O M Y C E S GRISEUS; STREPTOMYCES LAVENDULAE; STREPTOMYCES VENEZUELAE; S T R E P T O M Y C E S VIOLACEUS; STREPTOMYCIN; STREPTOSTASIN; STREPTOTHRICIN; STREPTOTHRICIN V I ; STREPTOTHRIX; SUBTENOLIN; SUBTILIN; S U B T I L I N C ; S U L F A C T I N ; S Y M P H O R I C A R P U S ORBICULATUS; SYMPLOCARPUS FOETIDUS; TARAXACUM O F F I C I N A L E ; TARDIN; T A X U S CANADENSIS; TERRAM Y C I N ; TERREIC ACID; T E T R A H Y M E N A G E L E I I ; T E T R A H Y M E N A VORAX; T H A L I C T R U M D I O I C U M ; T H U J A PLICATA; THYROID; TILLANDSIA U S N E O I D E S ; T R A G O P O G O N PRATENSIS; TRAMETES SERPENS; TRICHOPHYTON GYPSEUM; TRICHOPHYTON INTERDIGITALES; TRICHOPHYTON MENTAGROPHYTES; TRICHOPHYTON RUBRUM; TRICHOPHYTON TONS U R A N S ; T R I C H O P H Y T O N VIOLACEUS; T R I C H O T H E CIN; T R I F O L I U M HYBRIDUM; T R I F O L I U M PRAT E N S E ; T R I F O L I U M R E P E N S ; T R I L L I U M SESSILE; T Y P H A ANGUSTIFOLU; TYROCIDINE; TYROTHRIC I N ; U M B I L I C A R I A DELINEATA; U S T I N ; UVULARLA PERFOLIATA; VALERIANA PAUCIFLORA; V A L E R I A NELLA RADIATA; V E R B A S C U M T H A P S U S ; V E R B E N A A N G U S T I F O L U ; V E R O N I C A ARVENSIS; V E R O N I C A O F F I C I N A L I S ; V I B U R N U M O P U L U S ; V I C I A CRACCA; V I N C A M I N O R ; VIOLA PAPILIONACEA; VIOLAC E I N ; V I T I S LABRUSCA; W H E A T BRAN; X A N T H O M Y C I N S A AND B ; YEASTS; Y U C C A F I L A M E N TOSA; Z E B R I N A P E N D U L A ; Z I Z I A AUREA. F o r l i t -

erature see Arnstein et al., 1946a ( F u s a r i a ) ; Atkinson, 1949 (fungi and higher plants); Atkinson and Rainsford, 1946 (higher plants); Beal, 1947 ( f u n g i ) ; Brian and Hemming, 1947 ( f u n g i ) ; Burkholder and Evans, 1945 (lichens); Cardoso and Santos, 1948 (higher plants); Carlson et al., 1946 (higher p l a n t s ) ; Carlson and Douglas, 1948a (higher plants); Carlson, Douglas and Robertson, 1948 (higher plants); Carpenter, 1945 ( f u n g i ) ; Cook et al., 1947 ( F u s a r i a ) ; Cook and Lacey, 1945b ( f u n gi); Gaw and Wang, 1949 (higher plants); Gill-Carey, 1949a (Aspergilli); Gottshall et al., 1949 (higher plants); Hervey, 1947 ( f u n g i ) ; Little and Grubaugh, 1946 (vegetables); Lucas and Lewis, 1944 (higher p l a n t s ) ; Mathieson, 1946 ( f u n g i ) ; Melin and Wikén, 1946 (higher plants); Melin et al., 1947 ( M a r a s m i u s ) ; Osborn, 1943 (higher plants); Robbins et al., 1945 ( f u n g i ) ; Rosenfeld and ZoBell, 1947 (marine microorganisms); Sanchez et al., 1948 (woods); Schnell and Thayer, 1949 (higher plants); W i l k i n s , 1946a ( f u n g i ) ; Wilkins, 1946b ( f u n g i ) ; Wilkins, 1947a ( f u n g i ) ; Wilkins, 1947b ( f u n g i ) ; Wilkins, 1947c ( f u n g i ) ; Wilkins, 1948 ( f u n g i ) ; Wilkins and Harris, 1942 ( f u n g i ) ; Wilkins and Harris, 1943a ( f u n gi); Wilkins and Harris, 1944a ( f u n g i ) ; Wilkins and Harris, 1944d ( f u n g i ) . 2 Experiment a l i n f e c t i o n s , s e e ASPERGILLIC ACID; AYFIVIN; BACILLIN; BACITRACIN; B I F O R M I N ; BRAIN; CITRIN I N ; FUMIGACIN; GRISEIN; LITMOCIDIN; N E O M Y CIN; STREPTOMYCIN; STREPTOTHRICIN. 3 T r e a t -

ment of clinical infections caused by, see AUREOMYCIN;

POLYPORIN.

Staphylococcus cltreos, as test organism in vitro, see sp.;

ANTIBIOTIC 136; AUREOMYCIN; BACILLUS COPTIS CHINENSIS; FUMIGACIN; FUSCIN;

STEREOCAULON PASCHALE

G E O D I N ; G R A M I C I D I N ; K O J I C ACID; P S E U D O M O N A S F L U O R E S C E N S ; S U B T I L I N ; TYROCIDINE. F o r l i t e r -

ature see Rosenfeld and ZoBell, 1947 (marine microorganisms).

Staphylococcus hemolytic us áureos, as test org a n i s m in

vitro,

s e e ANACARDIC ACID.

Staphylococcus muscae, as test organism in vitro,

see

ACTINOMYCIN;

STREPTOTHRICIN.

Staphylococcus pyogenes. 1 As test organism in vitro, see L I C H E N I F O R M I N ; N I S I N . 2 Experimental infections, see LICHENIFORMIN. staphylophage, as test organism in vitro, see ANTIBIOTIC

H-3;

ASPERGILLUS

spp.

Statice gmelini, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Statice limonhim, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Steironema ciliatum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See O s b o m , 1943. Stellaria holostea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Stellaria media, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carolo vora, and Phytomonas tumefaciens. See Hayes, 1947. Stemona japónica, see S T E M O N A SESSILIFOLIA. Stemona sessilifolia (or S. japónica) a higher plant, concentrated aqueous extracts of the Chinese drug prepared f r o m the root of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus. See G a w and Wang, 1949. Stemphylium consortiale, as test organism in vitro,

s e e 5-METHOXY-P-TOLUQUINONE.

Stemphylium graminis, as test organism in vitro,

see

PINOSYLVINE.

Slenocarpus sinuatus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Stenomesson sp., a higher plant, extracts of the bulbs of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Stephania longa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Stephania rotunda, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

Stephenia cepherantha, see

CEPHERANTHIN.

Stereocaulon paschale, a l i c h e n , extracts of which are effective in vitro against Bacillus mycoides [1], B. subtilis [1,2], Sarcina lutea [1], and Staphylococcus aureus [1,2], and ineffective against Aerobacter aerogenes [1], Alcaligenes fecalis [1], Diplococcus pneumoniae [1], Escherichia coli [1,2], Proteus vulgaris [1], Serratia marcescens [1], Staph, albus [1], Streptococcus hemolyticus [I], and Strep, viridans [1], See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944.

Cross references are indicated by SMALL CAPITALS

[278]

STF.REUM

Stercum sp., a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Stereom abiettoum, a f u n g u s which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Stereom albobadium, a f u n g u s which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Stereum blcolor, a f u n g u s which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Stereum elegaus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Stereum fasciatum, a f u n g u s which is reported Staphylococa ) to be effective in vitro against cus aureus but not against Escherichia coli [I], and b ) to be ineffective against these two microorganisms [2]. T h e culture media of this f u n g u s are weakly inhibitory for Staph, aureus a n d / o r E. coli [3]. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1947a. Stereum frustulosum, a fungus which is reported a ) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b ) to inhibit Staph, aureus but not E. coli [21. T h e culture media of this fungus are weakly inhibitory for Staph, aureus and/or E. coli [3]. See [1] Hervey, 1947; (2| Robbins et al., 1945; [3] Wilkins, 1947a. Stereum fuscum, a f u n g u s which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1). It is also reported t o inhibit Staph, aureus a n d ' o r E.coli [2], See [1] Robbins et al., 1945; [2] Wilkins, 1947b. Stereum gausapatum, a fungus which is reported a ) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b ) to be ineffective against these two microorganisms [2, 3]. See [1] Robbins et al., 1945; [2] Hervey, 1947; [3] Wilkins, 1946b. As test organism in vitro, see ACTINOMYCES ANNULATUS; ACTINOMYCES FI.AVOVIRENS; ACTINOMYCES GOUGEROTI; ACTINOMYCES HALSTEDII; A C T I N O M Y C E S MADURAF.; A C T I N O M Y C E S

VIRIDOCHROMOGENUS. F o r literature see Alexopoulos and Herrick, 1942 (Actinomycetes). Stereum hirsutum, a f u n g u s which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1], b ) to inhibit Staph, aureus a n d / o r E. coli [2], and c) to be ineffective against these two microorganisms [3]. Extracts of the sporophores of this f u n g u s are ineffective against Staph, aureus [4, 5], E. coli [4, 5], and Pseudomonas aeruginosa [5]. See [1] Hervey, 1947; [2] Wilkins, 1946b; [3] Robbins et al„ 1945; [4] Mathieson, 1946; [5] Wilkins and Harris, 1 9 4 4 d . S e e a l s o HIRSUTIC ACIDS.

Stereum ¡Hudens, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Stereum lobatum, a fungus, the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus a n d / o r Escherichia coli. See Wilkins, 1947a. Stereum murrayl, a f u n g u s which is reported a) t o be effective in vitro against Staphylococ-

cus aureus and Escherichia coli [1,2] and b ) to be ineffective against these two microorganisms [3]. See [1] Hervey, 1947; [2] R o b bins et al., 1945; [3] Wilkins, 1947a. Stereum necator, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947a. Stereum ochraceoflavum, a f u n g u s which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Stereum pini, a fungus which is reported a ) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b ) to be ineffective against these two microorganisms [2,3]. See [1] Hervev, 1947; [2] R o b b i n s et al., 1945; [3] Wilkins, 1946b. Stereum purpureum, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b ) to be ineffective against these two microorganisms [2]. The culture media of this fungus are weakly inhibitory for Staph, aureus a n d / o r E. coli [3], Extracts of the s p o r o p h o r e s are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [4], See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1947a; [4] Wilkins and Harris, 1944d. As test organism in vitro, see ASPERGILLIC ACID; B E R B E R I N E ; B U R D O C K ; C H E I R O L I N E ; C L A V A C I N ; C L I O T O X I N ; M Y C O P H E N O L I C ACID; P E N I C I L LIC ACID; PROACTINOMYCIN; SPIRAEA; TYROT11RICIN.

Stereum rameale, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. The culture media of this fungus are strongly inhibitory for Staph, aureus a n d ' o r E. coli [2]. See [1] Robbins et al., 1945; [2] Wilkins, 1947a. See also RAMEAI.1N.

Stereum roseocarnum, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Robbins et al., 1945. Stereum r u f u m (?), a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See R o b b i n s et al.. 1945. Stercum rugosiusculum, a f u n g u s which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Robbins et al., 1945. Stereum rugosum, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b ) to be ineffective against these two microorganisms [2, 3], The liquid culture medium of this f u n gus inhibits Staph, aureus in dilutions no greater than 1:64 [1], Extracts of the s p o r o p h o r e s are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [4]. See [1] Robbins et al., 1945; |2] Hervey, 1947; [3] Wilkins, 1946b; [4] Wilkins and Harris. 1944d. Stereum sanguinolentum, a f u n g u s which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli ¡11, b ) to inhibit Staph, aureus but not E.coli |2|, and c) to be ineffective against these two microorganisms [3]. Extracts of the sporophores of this fungus inhibit Staph, aureus but not E. coli and Pseudomonas aeruginosa [41. Sec |I1 Hervev. 1947; [21 Robbins et al.. 1945; [3] Wilkins. 1946b: [4] Wilkins and Harris, 1944(1.

Cross references arc indicated

HV S M A L L

CAPITALS

[279] Stereum sericeum, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Robbins et al., 1945. Stereum spadkeum, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and/or Escherichia coli [1] and b) to be ineffective against these two microorganisms [2, 3]. Extracts of the sporophores of this fungus are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [41. See (1] Willdns, 1946b; [21 Robbins et al., 1945; [3] Hervey, 1947; [4] Wilkins and Harris, 1944d. Stereum subpileatum, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1,21. The culture media of this fungus are weakly inhibitory for Staph, aureus a n d / o r £ . coli [3]. See [1J Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1947a. Stereum sulcatum, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2]. The liquid culture medium of this fungus inhibits Staph, aureus in dilutions no greater than 1:64 [2], The fungus is also reported to inhibit Staph, aureus and/or E. coli [3]. See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1947b. Stereum umbrinum, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Robbins et al., 1945. Stereum vellereum, a fungus, the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus and/or Escherichia coli. See Wilkins, 1947a. sterigmatocystin, a thermolabile antibiotic derived f r o m the fungus Sterigmatocystis by centrifuging the supernatant from crushed mycelia. It is effective in vitro against Staphylococcus aureus. See Nekam and Polgar, 1948. Sterigmatocystis, a fungus which produces the a n t i b i o t i c , STERIGMATOCYSTIN.

Sterigmatocystis sp., a fungus which is effective in vitro against Alternaria sp. See Porter, 1924. Sterigmatocystis niduians, see NIDULINE. Steriphoma ellipticum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Steriphoma paradoxum, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Stevia satureiaefolia, a higher plant, extracts of which are ineffective against experimental malaria. See Spcncer et al., 1947. Stlfftia cbrysantha, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Stigmaphyllon ciliatum, a higher plant, aqueous extracts of which are ineffeciive in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Stokesia laevis, a higher plant, aqueous extracts of the root and entire plant of which are effective in vitro against Staphylococcus aureus while aqueous extracts of the seed, leaf, and stem are ineffective. Only aqueous extracts of the seed and root inhibit the spores of Neurospora crassa, and only aqueous extracts of the

STREPTOCOCCUS HEMOLYTICX'S

leaf inhibit Escherichia coli. See Schnell and Thayer, 1949. streptin, provisional designation of an antibiotic produced by an unidentified Streptomyces which resembles both S. lavendulae and S. reticulus-ruber. The active principle inhibits Mycobacterium tuberculosis, Escherichia coli, staphylococci, and streptococci. See Woodruff and Foster, 1946b. Streptobacillus moniliformis, experimental infections, see PENICILLIN.

Streptobacterium pian ta rum, as test organism in

vitro,

s e e PARASORBIC ACID.

Streptocarpus holstii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. streptococcal infections. 1 Clinical, see BACITRACIN; CITRININ; CILLIN.

streptococcal

2

Experimental,

subacute

bacterial

see

PENI-

endocarditis,

clinical, see STREPTOMYCIN.

streptococcus, groups A, B, D, and G, as test organisms in viiro, see AYFIVIN. Streptococcus sp., as test organism in vitro, see NOTALYSIN.

Streptococcus spp., as test organisms in

vitro,

s e e ANTISMEGMAT1S FACTOR; BACILLIN; BACILLUS s p . ; BACITRACIN; C O P T I S CHINENSIS; C O R TINARIUS ROTUNDISPORUS; FUMIGACIN; GLIOTOXIN; GRAMICIDIN S ; INSECTICIN; K O J I C ACID; LICHENIFORMIN; MICROCOCCIN; MOLD, RED, U N IDENTIFIED; NISIN; PENICILLIN; PSALLIOTA XANTHODERMA; STREPTIN; STREPTOSTASIN; SUBTENOI.IN; SULFACTIN; TYROCIDINE; USTIN.

Streptococcus agalactiae, as test organism

in

vitro, s e e BACILLUS LARVAE; NISIN; PERSOONIA PINIFOLIUS; POLYMYXINS; PSALLIOTA XANTHODERMA.

Streptococcus vitro,

cremoris, as test

organism

in

s e e DIPLOCOCCIN; NISIN.

Streptococcus duran s, as test organism in vitro, s e e O N C O P E L T U S FASCIATUS.

Streptococcus fecalis. 1 As test organism in vitro, s e e ACTIDIONE; ANTIBIOTIC H - 3 ; A S A R U M CANADENSE V. REFLEXUM; ASPERGILLIC ACU>; ASPERGILLIN; AUREOMYCIN; A Y F I V I N ; CENTAUREA MACULOSA; CHLORAMPHENICOL; DICOUMARIN; EPIDERMOPHYTON FLOCCOSUM; E S C H E RICHIA COLI; GRAMICIDIN; K O J I C ACID; L E P T O TAENIA DISSECTA; LUPULON AND H U M U L O N ; M I CROCOCCIN; NEOMYCIN; NOCARDIA GARDNERI; PENICILLIN; PERSOONIA PINIFOLIUS; POLYMYXINS; PSALLIOTA XANTHODERMA; R H U S HIRTA; STREPTOMYCES ANTIBIOTICUS; STREPTOMYCES GRISEUS; STREPTOMYCES LAVENDULAE; STREPTOMYCES VENEZUELAE; STREPTOMYCIN; SUBTILIN; SULFACTIN; TERRAMYCIN; T H U J A PLICATA; T R I CHOPHYTON MENTAGROPHYTES; T R I C H O P H Y T O N TONSURANS; TRICHOPHYTON VIOLACEUM; TYRO-

CIDINE; WHEAT BRAN. F o r l i t e r a t u r e s e e R o s e n -

feld and ZoBell, 1947 (marine microorganisms). 2 Treatment of clinical infections caused by,

s e e AUREOMYCIN;

PENICILLIN;

STREPTOMY-

CIN; TERRAMYCIN. 3 Treatment of subacute bacterial endocarditis, clinical, caused by, see AUREOMYCIN;

STREPTOMYCIN.

AUREOMYCIN;

STREPTOMYCIN.

urinary

infections, clinical,

4

Treatment

caused

by,

of

see

Streptococcus hemolytkus. 1 See STREPTOSTASIN.

2 A s test o r g a n i s m in vitro, see ALLICIN; ANTIBI-

OTIC 1 3 6 ; ANTIBIOTIC X G ; A R C T I U M M I N U S AND ONOPORDON TAURICUM; ASARUM CANADENSE v. REFLEXUM; ASPERGILLIC ACID; AUREO-

Cross references are indicated by SMALL CAPITALS

STREPTOCOCCUS

I N F R E Q U E N TA N S

[2*0]

M Y C I N ; BACILLUS BREVIS; BACITRACIN; BORRELIDIN; BUTTERCUP; CHLORAMPHENICOL; COPTIS CH1NENSIS; CORYLOPHYLINE; EPIDERMOPHYTON FLOCCOSUM; FREQUENTIC ACID; FUMIGACIN; GRAMICIDIN; HEART; IODININ; JAVANICIN; LITMOCIDIN; MICROSPORUM AUDOUINI; MYCETIN; NIDULINE; NOTATIN; PENICILLIN; PERSOONIA PINIFOLIUS; P O L Y M Y X I N S ; PROTOANEMONIN; PSALLIOTA XANTHODERMA; PSEUDOMONAS AERUGINOSA; PYO COMPOUNDS; SPLEEN; STREPTOMYCES VENEZUELAS; STREPTOMYCIN; STREPTOTHRICIN; TERRAMYCIN; TERREIC ACID; T H U J A PLICATA; THYROID; TILLANDSIA USNEOIDES; T R I CHOPHYTON GYPSEUM; TRICHOPHYTON INTERDIGITALES; TRICHOPHYTON MENTAGROPHYTES; TRICHOPHYTON RUBRUM; TRICHOPHYTON TONSURANS; TRICHOPHYTON VIOLACEUM; TYROCIDINE; TYROTHRICIN. F o r literature see B u r k h o l d e r a n d E v a n s , 1945 ( l i c h e n s ) . 3 E x p e r i m e n t a l i n f e c t i o n s , see A R C T I U M MINUS AND ONOPORDON TAURICUM; ASPERGILLIC ACID; AUREO M Y C I N ; BACITRACIN; BORRELIDIN; CHLORAMPHENICOL; FUMIGACIN; GRAMICIDIN; NISIN; PENICILLIN; STREPTOMYCIN; STREPTOTHRICIN; TERRAMYCIN; THUJA PLICATA; TYROTHRICIN. 4 T r e a t m e n t o f c l i n i c a l i n f e c t i o n s caused b y , see AUREOMYCIN; CHLORAMPHENICOL; PENICILLIN; STREPTOMYCIN; TERRAMYCIN. 5 T r e a t m e n t o f subacute b a c t e r i a l e n d o c a r d i t i s , c l i n i c a l , caused b y , see AUREOMYCIN. Streptococcus infrequentans, as test o r g a n i s m in vitro, see CHLORAMPHENICOL. Streptococcus lactls, a m i c r o o r g a n i s m which is i n e f f e c t i v e in vitro against Basisporum gal¡arum, Sclerotium rolfsii, and Glomerella cingulata. S e e P o r t e r , 1932. S e e also NISIN. A s test o r g a n i s m in vitro, see BACILLUS sp.; BACILLUS VULGATUS; CHLORAMPHENICOL; DIPLOCOCCIN; GLIOTOXIN; LUPULON AND H U M U LON; NOCARDIA GARDNERI; STREPTOMYCES ANTIBIOTICUS; STREPTOMYCES GRISEUS; STREPTOMYCES LAVENDULAE; STREPTOMYCES VENEZUELAE; STREPTOTHRICIN; SUBTILIN. Streptococcus Uqoefaciens, as test o r g a n i s m in vitro, see BACILLUS sp. Streptococcus mastitidis, as test o r g a n i s m in vitro, see BACILLUS sp.; GRAMICIDIN; TYROCIDINE. Streptococcus mitfa, a m i r c r o o r g a n i s m , some strains o f w h i c h , isolated f r o m saliva, inhibit Corynebacterium diphtheriae [ 1 ] . T h i s antibio t i c activity is d u e t o t h e p r o d u c t i o n o f hyd r o g e n p e r o x i d e [ 2 ] . See [ 1 ] T h o m p s o n a n d S h i b u y a , 1946; [ 2 ] T h o m p s o n a n d J o h n s o n , 1947. A s test o r g a n i s m in vitro, see AURF.OMYCIN. Streptococcus n o n h e m o l y t i c ! » , as test o r g a n i s m in vitro, see CHLORAMPHENICOL. Streptococcus pneumoniae. 1 A s test o r g a n i s m in vitro, see AYFIVIN; CLAVACIN; FUMIGACIN; NOTATIN; PENICILLIN; PROACTINOMYCIN. 2 E x p e r i m e n t a l i n f e c t i o n s , see NISIN. Streptococcus pneumoniae, types 1, 2, S, a n d 7, as test o r g a n i s m s in vitro, see MICROCOCCIN. Streptococcus pneumoniae, types 1, 3, 6, 8, 19, a n d t w o untyped strains, as test o r g a n i s m s in vitro, see AYFIVIN. Streptococcus pyogenes. 1 A s test o r g a n i s m in vitro, see ACTIDIONE; ACTINOMYCIN; ALVEIN; ANACARDIC ACID; ASPERGILLIC ACID; ASPERGILLIN; AUREOMYCIN; AVENACEIN; AYFIVIN; BACILIPIN A AND B ; BACILLUS sp.; BACILYSIN; BACITRACIN; CARNEOLUTESCIN; CENTAUREA MACULOSA; CHLORBLLIN; CLAVACIN; CREPIN; DESTRUIN; DICOU-

MARIN; FRUCTIGENIN; FUMIGACIN; FUSCIN; OEODIN; GLIOTOXIN; H E R Q U E I N ; HIRSUTIC ACIDS; JAVANICIN; LATERITIINS; LATEROSPORIN A AND B ; LEPTOTAENIA DISSECT A; LEPTOTAENIA M U L T I FEDA; MICROCOCCIN; MUSARIN; MYCELIANAMIDE; MYCOPHENOLIC ACID; NUDIC ACID A AND B ; PENATIN; PENICILLIN; PHTHIOCOL; POLYPEPTIN; POLYPORIN; PROACTINOMYCIN; PSALLIOTA sp.; RHUS HIRTA; SAMBUCININ; SPLEEN; STAPHYLOCOCCUS AUREUS; STREPTOMYCES AUREOFACIENS; STREPTOMYCES VENEZUELAE; SUBTENOLIN; SUBTILIN; SULFACTIN; TETRAHYMENA GELEII. F o r literature see A r n s t e i n et al., 1946a ( F u s a r i a ) ; C o o k et al., 1947 ( F u s a r i a ) . 2 E x p e r i m e n t a l i n f e c t i o n s , see AYFIVIN; FUMIGACIN; LICHENIFORMIN; LUPULON AND H U M U L O N ; NISIN; PROACTINOMYCIN; SUBTILIN. 3 T r e a t m e n t o f c l i n i c a l i n f e c t i o n s caused b y , see POLYPORIN. Streptococcus salivarius, as test o r g a n i s m in vitro, see BACILLUS sp.; PHTHIOCOL. Streptococcus viridans. 1 A s test o r g a n i s m in vitro, see ALLICIN; A R C T I U M MINUS AND O N O PORDON TAURICUM; ASARUM CANADENSE V. REFLEXUM; AYFIVIN; BUTTERCUP; CITRININ; CLAVACIN; DICOUMARIN; FUMIGACIN; FUSCIN; GLIOTOXIN; LEPTOTAENIA DISSECTA; LICHENIFORMIN; L I T M O C I D I N ; MICROCOCCIN; MYCELIANAMIDE; MYCOSUBTILIN; PENICILLIN; PERSOONIA PINIFOLIUS; POLYMYXINS; PROACTINOMYCIN; PROTOANEMONIN; PSALLIOTA XANTHODERMA; PUROTHIONIN; PYO COMPOUNDS; RANUNCULUS OCCIDENTALS; RHUS HIRTA; STREPTOMYCIN; STREPTOTHRICIN; SUBTILIN; TARDIN; TETRAHYMENA GELEII; THUJA PLICATA; TYROTHRICIN; in vivo, see BLOOD. F o r literature see B u r k h o l d e r a n d E v a n s , 1945 ( l i c h e n s ) . 2 E x p e r i m e n t a l i n f e c tions, see CHLORAMPHENICOL. 3 T r e a t m e n t o f clinical i n f e c t i o n s caused b y , see AUREOMYCIN; CHLORAMPHENICOL; P E N I C I L L I N ; POLYPORIN; STREPTOMYCIN; TERRAMYCIN. streptolin, an antibiotic substance o b t a i n e d f r o m an unidentified species o f Streptomyces design a t e d as Streptomyces 11. I t has b e e n o b t a i n e d as the h y d r o c h l o r i d e and as t h e c r y s t a l l i n e helianthate. I n s o m e respects s t r e p t o l i n r e s e m b l e s s t r e p t o m y c i n and streptothricin. T h e m . p . o f the helianthate d e r i v a t i v e is 2 0 7 ° - 2 1 1 ° C . ( u n c o r r . , d e c o m p . ) . T h e unit o f s t r e p t o l i n is that amount which, when dissolved in 1 cc o f a 0 . 7 5 % p e p t o n e , 0 . 2 5 % yeast e x t r a c t b r o t h at p H 7.2, will just inhibit the g r o w t h o f Escherichia coli H 5 2 d u r i n g an 18-20 hr i n c u b a t i o n at 3 7 ° C . w h e n t h e i n o c u l u m is 0.00005 c c o f a 20-hr b r o t h culture p e r cc. SPECTRUM.—Streptolin the f o l l o w i n g o r g a n i s m s :

Organism Aerobacter aerogenes Aerobacter polymyxa Bacillus cereus Bacillus fusilormis Bacillus megatherium Bacillus mycoides Escherichia coli H52 Proteus vulgaris Pseudomonas aeruginosa Pseudomonas fluorescens

is

inhibitory

for

Inhibitory concentration i n units/cc 3.3 1.0 3.3 0.1 0.3 10.0 1.0 3.3 10.0 33.0

TOXICITY. — W h e n a crude preparation c o n t a i n i n g 30,000 units/mg is i n j i.v. i n t o 2 0 - g m m i c e , 6 0 % survive 0.13 m g and 3 7 % survive 0.2 m g . S e e R i v e t t and P e t e r s o n , 1947.

C r o s s r e f e r e n c e s are indicated b y SMALL CAPITALS

[281] streptolycin, an antibiotic substance produced by a strain of Sireplomyces lavendulae. See H u t c h i s o n et al., 1949. Streptomyces, see also ACTINOMYCES. Streptomyces 11, see STREPTOLIN. Streptomyces 94, see XANTHOMYCINS A AND B. Streptomyces spp., unidentified actinomycetes of the genus Streptomyces, one species of which is effective in vitro against Bacillus subtilis. A q u e o u s extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. See

also

ANTIBIOTIC " F " ;

see

RANUNCULUS

BORRELIDIN;

NEOMY-

CIN; STREPTOLIN. As test organisms in OCCIDENTALS.

vitro,

Streptomyces AI "Tai," as test organism in vitro, see MICROCOCCIN. Streptomyces albus, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueo u s extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. Streptomyces albus v. ochraleuceus, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. Streptomyces annulatus, an actinomycete which is effective in vitro against Bacillus subtilis. A q u e o u s extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. Streptomyces antibioticus, an actinomycete which is effective in vitro against Bacillus subtilis, Micrococcus jlavus, Mycobacterium smegma, Staphylococcus aureus. Streptococcus fecalis, and Strep, lactis; and fails to inhibit Aerobacter aerogenes, Alcaligenes jecalis, Escherichia coli, and Pseudomonas aeruginosa [1]. It is also reported that this organism is ineffective against B. subtilis, while aqueous extracts of it inhibit B. subtilis [2], See [1] Gottlieb et al., 1948; [2] Waksman, 1945. See also ACTINOMYCIN. Streptomyces aurantiacus, an a c t i n o m y c e t e which is inhibitory in vitro for the following organisms: Bacillus megatherium Bacillus mesentericus Bacillus mycoides Bacillus subtilis Corynebacterium sp. Micrococcus candicans Micrococcus luteus Micrococcus lysodeikticus Micrococcus roseus Micrococcus ruber Mycobacterium citreum Mycobacterium phlei Mycobacterium smegma Mycobacterium tuberculosis Nocardia alba Nocardia corallina Nocardia rubra Sarcina lutea Staphylococcus aureus It is ineffective in vitro against the following: Azotobacter chroococcum Azotobacter vinelandii Bacillus tumescens Escherichia coli Proteus vulgaris Pseudomonas aeruginosa Pseudomonas fluorescens Kadiobacter sp.

STREPTOMYCES CLOBIGISPORUS

Rhizobium leguminosarum Serratia marcescens See W a k s m a n , 1945. Streptomyces aureofaciens, an a c t i n o m y c e t e which produces the antibiotic, AUREOMYCIN. The organism is effective in vitro against the following: Aerobacter aerogenes Bacillus cereus Bacillus subtilis Brucella abortus Coccobacillus sp. Escherichia coii Klebsiella pneumoniae Mycobacterium tuberculosis Neisseria catarrhalis Proteus vulgaris pullorum Salmonella Salmonella typhi Shigella gallinarum Staphylococcus aureus Streptococcus pyogenes Streptomyces griseus It is ineffective against Aspergillus niger, Penicillium chrysogenum, Pseudomonas aeruginosa, and Serratia marcescens. It is itself inhibited by P. chrysogenum and Streptomyces griseus. See Duggar, 1948. Streptomyces aureus, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. Streptomyces bovis, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. Streptomyces califomicus, an a c t i n o m y c e t e which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. Streptomyces Candidus, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are also effective against B. subtilis. Sec W a k s m a n , 1945. Streptomyces cellulosae, an actinomycete which is effective in vitro against Bacillus subtilis. A q u e o u s extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. Streptomyces coeilcolor, an actinomycete which is effective in vitro against Bacillus subtilis. See W a k s m a n , 1945. As test organism in vitro, s e e L U P U L O N AND H U M U L O N .

Streptomyces cretaceus, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. Streptomyces EIr., see ANTIBIOTIC E h . Streptomyces fradiae, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. See also NEOMYCIN. Streptomyces globigisponis, an actinomycete which is effective in vitro against Nocardia corallina and is ineffective against the following: Azotobacter chroococcum Azotobacter vinelandii Bacillus mesentericus Bacillus mycoides Bacillus subtilis

Cross references are indicated by SMALL CAPITALS

STREPTOMYCES CRISEOCARNEUS

[ 2S2 ]

Bacillus tumescent Corynebacierium sp. Escherichia coli Micrococcus candicons Micrococcus luteus Micrococcus lysodeikticus Micrococcus roseus Micrococcus ruber Mycobacterium citreum Mycobacterium phlei Mycobacterium smegma Mycobacterium tuberculosis Nocardia alba Nocardia rubra Proteus vulgaris Pseudomonas aeruginosa Pseudomonas jluorescens Radiohacter sp. Rhizobium leguminosarum Sarcina lutea Serratia marcescens Staphylococcus aureus See Waksman, 1945. Streptomyces griseocarneus, see HYDROXYSTREPTOMYC1N.

Streptomyces griseus, an actinomycete, various strains of which produce the antibiotics ACTIDIONE,

ANTIBIOTIC

3510,

GRISE1N,

and

STREP-

TOMYCIN. I t a l s o p r o d u c e s ANTIBACILLIN. O n e

strain is reported to be effective in vitro against the following organisms [1]: Aerobacter aerogenes Alcaligenes jecalis Bacillus subtilis Escherichia coli Micrococcus jlavus Mycobacterium smegma Pseudomonas aeruginosa Staphylococcus aureus Streptococcus lactis A n o t h e r strain is reported t o be effective in vitro against Nocardia corallina and to be ineffective against the following organisms [2]: Azobacter chroococcum Azobacter vinelandii Bacillus mesentericus Bacillus mycoides Bacillus subtilis Bacillus tumescens Corynebacierium sp. Escherichia coli Micrococcus candicans Micrococcus luteus Micrococcus lysodeikticus Micrococcus roseus Micrococcus ruber Mycobacterium citreum Mycobacterium phlei Mycobacterium smegma Mycobacterium tuberculosis Nocardia alba Nocardia corallina Nocardia rubra Proteus vulgaris Pseudomonas aeruginosa Pseudomonas jluorescens Radiobacter sp. Rhizobium leguminosarum Sarcina lutea Seiratia marcescens Staphylococcus aureus Aqueous extracts of one strain which is effective in vitro against Bacillus subtilis are ineffective against B. subtilis [2], The strain

which produces streptomycin also produces an unnamed antibiotic substance which can be obtained f r o m the culture liquor by adsorption on charcoal and elution with acetone, methanol, or butanol, followed by vacuum distillation and purification with butanol. This agent is relatively thermostable but loses activity on prolonged storage at 4 C. [3]. The crude active substance inhibits Streptomyces logos at 1:250,000 and is also effective against Corticium solani, Cryptococcus neoformans, and Saccharomyces spp. Bacillus subtilis, E. coli, Staph, aureus, and other bacteria are unaffected. Mice weighing 40 gm tolerate daily doses of 20 mg of a c r u d e preparation [3], See Gottlieb et al., 1948; [2] W a k s m a n , 1945: [3] Lumb, 1949. As test organism in vitro, s e e ALLICIN: FRADICIN; L E P T O T A E N I A SECTA; S T R E P T O M Y C E S AUREOFACIENS.

DIS-

Streptomyces halstedii, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. Streptomyces hominis, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. Streptomyces lavendulae, an actinomycete, one strain of which is effective in vitro against Bacillus subtilis. Aqueous extracts of this strain are also effective against B. subtilis [1], Another strain of this organism is reported to be effective in vitro against the following [2]: Aerobacter aerogenes A Icaligenes jecalis Bacillus subtilis Escherichia coli Micrococcus flavus Mycobacterium smegma Pseudomonas aeruginosa Staphylococcus aureus Streptococcus jecalis Streptococcus lactis See [1] Waksman, 1945; [2] Gottlieb et al., 1 9 4 8 . S e e a l s o ANTIBIOTIC 1 3 6 ; ANTIBIOTIC " V " ; LAVENDULIN; S T R E P T I N ; S T R E P T O L I N ; S T R E P T O LYCIN; STREPTOTHRICIN; STREPTOTHRICIN VI; VALICID1N.

Streptomyces lipmanii, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. Streptomyces logos, as test organism in vitro, s e e STREPTOMYCES

CRISEUS.

Streptomyces microflavus, an actinomycete which is effective in \itro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See W a k s m a n , 1945. Streptomyces odorifer, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See Waksman, 1945. Streptomyces pelletieri, as test organism in vitro, see LUPULON

AND

HUMUION.

Streptomyces praecox, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See W a k s m a n , 1945. Streptomyces reticuli, an actinomycete which is effective in vitro against Bacillus subtilis. Aqueous extracts of this organism are ineffective against B. subtilis. See W a k s m a n , 1945. Streptomyces rimosus, see TERRAMYCIN.

Cross references are indicated by SMALL CAPITALS

[283] Streptomyces roseus, an actinomycete which is effective in \itro against Bacillus subiilis. Aqueous extracts of this organism are also effective against B. subiilis. See Waksman, 1945. Streptomyces ruber, an actinomycete which is effective in vitro against Bacillus subiilis. Aqueous extracts of this organism are ineffective against B. subiilis. See Waksman, 1945. Streptomyces rutgersensis, an a c t i n o m y c e t e which is effective in vitro against Bacillus subiilis. Aqueous extracts of this organism are ineffective against B. subiilis. See Waksman, 1945. Streptomyces sampsonii, an actinomycete which is effective in v uro against Bacillus subiilis. Aqueous extracts of this organism are ineffective against B. subiilis. See Waksman, 1945. Streptomyces saprophytics, an actinomycete which is effective in viiro against Bacillus subiilis. Aqueous extracts of this organism are ineffective against B. subiilis. See Waksman, 1945. Streptomyces scabies, an actinomycete which is effective in \iuo against Bacillus subiilis. Aqueous extracts of this organism are ineffective against B. subiilis. See Waksman, 1945. Streptomyces setonii, an actinomycete which is effective in vitro against Bacillus subiilis. Aqueous extracts of this organism are ineffective against B. subiilis. See Waksman, 1945. Streptomyces tetanusemus, an a c t i n o m y c e t e which is effective in vitro against Bacillus subiilis. Aqueous extracts of this organism are ineffective against B. subiilis. See Waksman, 1945. Streptomyces venezuelae, n. sp. [1], the actinomycete which produces CHLORAMPHENICOL ("chloromycctin"). The organism is ineffective in vitro against Pseudomonas aeruginosa [2] but inhibits the following in vitro: Aerobacter aerogenes [2] Agrobacterium lumefaciens [2] Alcaligenes jecalis [2] Bacillus globigii [2) Bacillus mycoides [3] Bacillus subiilis [2, 3] Brucella abortus [2, 3] Escherichia coli [2, 31 Klebsiella pneumoniae (3] Micrococcus flavus [31 Mycobacterium smegma [2] Mycobacterium tuberculosis hominis [2, 3] Pasteurella muhicoides [2] Proteus vulgaris [21

STREPTOMYCIN

Salmonella pullorum [2] Salmonella scholtmuelleri [2, 3] Salmonella typhi [2] Serratia marcescens [2] Shigella paradysenteriae [2, 3] Staphylococcus aureus [2, 3] Streptococcus fecalis [2] Streptococcus hemolyticus [2] Streptococcus lactis [2] Streptococcus pyogenes [2, 3] See [1] Ehrlich et al., 1948; [2] Gottlieb et al.. 1948; [3] Ehrlich et al., 1947. Streptomyces vfolaceus, an actinomycete which inhibits the following organisms in vitro: A zotobacter chroococcum A zotobacter vinelandii Bacillus megatherium Bacillus mesentericus Bacillus mycoides Bacillus subiilis Bacillus tumescens Corynebaclerium sp. Micrococcus candicans Micrococcus luteus Micrococcus lysodeikticus Micrococcus roseus Micrococcus ruber Mycobacterium citreum Mycobacterium phlel Mycobacterium smegma Mycobacterium tuberculosis Nocardia alba Nocardia corallina Nocardia rubra Sarcina lutea Staphylococcus aureus It is ineffective against the following: Escherichia coii Proteus vulgaris Pseudomonas aeruginosa Pseudomonas fluorescens Radiobacter sp. Rhizobium leguminosarum Serratia marcescens See Waksman, 1945. streptomycin, a crystalline antibiotic produced by Streptomyces griseus [1] and Streptomyces bikiniensis [2, 3]. It is isolated f r o m fermentation liquors by acidifying to pH 2, decolorizing with carbon, adsorbing on carbon at pH 7, eluting with dilute acetone at pH 2.5, and precipitating by increasing the concentration of acetone. When sulphuric acid is used as the acidifying agent, the product is strep-

HjN—C

HJOH Cross references are indicated by SMALL CAPITALS

STREPTOMYCIN

[2S4]

tomycin sulphate; the hydrochloride may be obtained by using hydrochloric acid for acidification. Purification is effected by chromatographic separation o n an alumina column [4], Streptomycin is soluble in water and insoluble in ether, acetone, and chloroform [5]. Solutions of streptomycin lose their activity on exposure to heat, acid, or alkali; optimum stability is exhibited at 28°C. and p H 3-7. Dry neutral salts of this agent retain their activity f o r long periods when stored at S0°C. [6]. Streptomycin is inactivated by cysteine [7J. For structural f o r m u l a of streptomycin [8] see p. 283. Catalytic hydrogenation of streptomycin results in dihydrostreptomycin, which is very similar t o streptomycin in biological properties but is m o r e stable and is not affected by cysteine [9]. Acid hydrolysis of streptomycin yields streptidine (1,3-diguanido-2,4,5,6-tetrahydroxycycloh e x a n e ) and streptobiosamine. Acid hydrolysis of streptobiosamine yields N-methyl-L-glucosamine, while alkaline hydrolysis of streptidine yields streptamine (l,3-diamino-2,4,5,6-tetrahydroxycyclohexane) [6]. SPECTRUM. — O r g a n i s m s susceptible to streptomycin develop both resistance to and dependence on this agent [10, 11, 12]. In addition, susceptible organisms sometimes have naturally resistant variants [13], Penicillin and streptomycin exhibit a synergistic effect both in vivo [14] and in vitro [15]. B A L (2,3-dimercaptopropanol) enhances the bacteriostatic action of streptomycin on mycobacteria but not on Micrococcus lysodeikiicus, as is shown in the following table [16]:

Organism Micrococcus Ivsodeikticus Mycobacterium tuberculosis bovis Mycobacterium tuberculosis hominis H37Rv Mycobacterium tuberculosis hominis R1 Mycobacterium sp. (nonpathogenic)

Effective level of streptomycin Concenwith without tration BAL BAL of BAL 1:2x1t) 3

1:8x10 s

1:10«

1:64x10 s

1:32x10 s

1:10 s

1:32x10 s

1:8x10 s

1:10 s

1:64x10*

1:16x10 s

1:10 s

1:32x10 s

1:32x10 s

1:10 s

T h e following bacteria are inhibited in vitro by streptomycin in the concentrations shown: Inhibitory concentration in micrograms'cc Bacteria 2.5-more than Aerobacter spp. 100 [17] 0.13 [18] Bacillus mycoides 0.25 [18] Bacillus subtilis 2,500 - 4,000 [19] Bacteroides fragilis Bacteroides funduliformis 1,500-3,000 [19] 1 . 0 - 2 . 5 [20] Brucella abortus 1 . 0 - 2 . 5 [20] Brucella melitensis 1 . 0 - 2 . 5 [20] Brucella suis 5.0 [17] Citrobacter spp. Diplococcus pneumoniae 2 . 0 - 1 2 . 5 [17] 0.25 [18], 6.25 Escherichia coli [17], 7.5-25 [21]

Inhibitory concentration in micrograms/cc Escherichia 2.5 [17] Hemophilus 1 . 0 - 3 . 0 [21] Hemophilus more t h a n 25 [21] Hemophilus 3.0 [21] Klebsiella 0.13 [18], 0 . 6 2 - 5 . 0 [17] 0.25 [18] Mycobacterium phlei 1.0 [18] Mycobacterium smegma 200 [18] Photobacterium ftscheri 5.0 [17] Proteus sp. 5 - 2 5 [17] Proteus mirabilis 5.0 [17] Proteus vulgaris Pseudomonas aeruginosa 4.0 [18], 25-more than 100 [17], 100-200 [21] 0 . 2 5 - 2 0 0 [21] Salmonella spp. 25 - 75 [21] Salmonella typhi 25 [21] Shigella spp. 2.0 [17] Staphylococcus albus 0.03 [18], Staphylococcus aureus 2 . 0 - 1 2 . 5 [17] Streptococcus fecalis 1 0 - 5 0 [17] Streptococcus hemolyticus 6 . 2 - 1 0 0 [17] Streptococcus viridans 3 . 1 - 1 2 . 5 [17] Bacteria communior influenzae parapertussis pertussis pneumoniae

Streptomycin, in in vitro tests run in thioglycolate medium, inhibited Clostridium septicum. In preliminary prophylactic trials in mice, CI. septicum spores diluted in 2 . 5 % CaCls solution were introduced under the skin of the back and treatment was given at the same site immediately afterward and at 5 and 23 hr. For about 5 0 % protection, doses of 50 m g / k g of streptomycin were required. Attempts are being made to establish infections with CI. welchii, CI. novyi, and CI. tetani in order to extend the comparisons [43]. In a series of in vitro tests with streptomycin, in concentrations varying f r o m 2.5 to 250 m i c r o g r a m s / c c against Cryptococcus neoformans, n o inhibition resulted [44]. Streptomycin also inactivates various bacteriophages [22], It is ineffective against Ascaris suis, Leishmania donovani, and Trypanosoma equiperdum; a dilution of 1:2,500 kills Endameba histolytica [23]. Fifty to 200 m g / c c is effective in vitro against Histoplasma capsulatum [24]. Streptomycin has very little antifungal activity; in some instances it enhances the growth of fungi in vitro [25], It has less than 45 dilution units of activity per gm against the following saprophytic and pathogenic fungi [26]: A spergillus clavatus Candida albicans Cryptococcus neoformans Dematium sp. Fusarium sp. Penicillium luteum purpurogenum Trichophyton mentagrophytes The unit of streptomycin is 1 microgram [27], EXPERIMENTAL TOXICITY AND PHA RMA COLOG Y.—Intravenous i n j of about 200 m g / k g is fatal t o mice. Single s.c. injs of 800 m g / k g are lethal for 2 0 % and 2,200 m g / k g , for 100%. After i.v. inj of lethal quantities mice show respiratory difficulties, uncon-

Cross references are indicated by SMALL CAPITALS

[285] sciousness, and, finally, respiratory death within 5 m i n . There are no delayed deaths. Fatal s.c. injs cause restlessness, respiratory difficulties, a n d c o m a which may last for a day before d e a t h occurs. As with i.v. inj, there are no delayed deaths among mice which recover. Single oral doses of 5,000 m g / k g do not cause d e a t h in mice. Mice are f o u n d to survive without ill effect 5 s.c. injs per day of 200 m g / k g each for 6 days, or 1,500 m g / k g per d a y in the diet for a month. Rats are not affected by s.c. inj of 100 m g / k g per day in three daily doses for 72 days. They also survive 400 m g / k g per day s.c. for 8 days, or the same dose i.v. for 6 days. Guinea pigs survive u p to 60 m g / k g per day in three daily s.c. doses f o r 6-8 wk [28]. Local application of streptomycin to the eyes of rabbits causes only occasional redness of the conjunctiva [28], Subcutaneous inj of 300,000 u n i t s / k g per day leads to neurotoxic s y m p t o m s in rabbits in 11 days. The same effect is seen in 7 days when the dose is increased t o 450,000 u n i t s / k g s.c., and within 1 h r following intracisternal inj of 1,000-1,250 u n i t s / k g [29], C h i c k s fed streptomycin at the rate of 50,000 u n i t s / 1 0 0 gm of diet show no signs of toxicity [30], D o g s receiving daily i.m. injs of 10,000 u n i t s / k g develop neurotoxic symptoms in 20 days; the same effect is noted 1 hr after intracisternal inj of 1,000 units/kg [29], When given i.m. inj of 170 m g / k g per day in f o u r daily doses, dogs develop ataxia, weaving of the head, tail-chasing, and weakness, but no manifest deafness. At autopsy on the 28th day, liquefaction necrosis of the ventral cochlear nuclei of the eighth cranial nerve is f o u n d . N o lesions are noted in the dorsal cochlear nuclei [31], Large doses of streptomycin in experimental animals also cause renal and hepatic damage [29, 31, 32], A f t e r i.v. inj of 20 m g / k g in the dog, peak plasma concentrations are reached almost immediately; after i.m. inj, the peak plasma concentration is reached in 1-2 hr. Streptomycin is excreted in the urine of dogs to the extent of 68-80% in 6-8 hr after i.v. or i.m. administration; a total of 86-88% is excreted in 24 hr [33], Streptomycin appears to be distributed in extracellular water [33], EXPERIMENTAL CLINICAL RESULTS. —Daily ingestion of 30,000 or 300,000 units/kg per day by mice results in reduction of colif o r m and non-lactose-fermenting organisms in the feces. There is no evidence of the development of resistance by these organisms [34], When given in a total dose of 16 mg over a period of 6 hr, streptomycin protects guinea pigs completely f r o m massive Corynebacierium diphtheriae infections [35]. Three s.c. doses of 10 m g / k g each given over a period of 24 hr prevent d e a t h in 100% of 20-22 gm mice infected with Kleb. pneumoniae. Only 80% protection is afforded when the dose is reduced to 8 m g / k g [17], Ninety-one and six tenths percent of mice infected intracerebrally with a pneumolropic pasteurella survive when given three 0.1 g m / k g s.c. injs of streptomycin over a period of 48 hr. Delaying treatment f o r 6-10

STREPTOMYCIN

hr after infection reduces the n u m b e r of survivors [36]. In pneumococcal infections in mice, 3 s.c. injs of 80 m g / k g each prevent d e a t h in 100% of cases [17]. C r u d e streptomycin administered parenterally to mice at the rate of 2.5 m g every 6 hr for 3 days is effective against mixed infection with Pr. vulgaris and an anaerobic streptococcus [5]. Subcutaneous inj of 200 units results in 8 6 % survival in mice infected with Salm. schoitmuelleri, while 400-unit doses protect only 5 0 % when the infecting organism is Salm. typhi. Twelve and one-half units s.c. protect 9 5 % of mice f r o m Staph, aureus infections; 80% protection results with oral doses of 400 units [27]. In Strep, hemolyticus infections in mice, there is 70% survival a f t e r three s.c. injs of 100 m g / k g each over a period of 24 hr [17]. Streptomycin has been shown t o be without effect in experimental syphilis in rabbits [37]. It is also ineffective in e m b r y o n a t e d h e n ' s eggs infected with toxoplasmosis [38]. Although the presence of potassium iodide does not alter the potency of streptomycin against mycobacteria in vitro, tuberculous guinea pigs show a higher survival rate when treated with potassium iodide and streptomycin than when treated with streptomycin alone [39]. Streptomycin is also of value in the treatment of experimental infections due t o Br. abortus, Ps. aeruginosa, and Shig. gallinarum [5], CLINICAL TOXICITY AND PHARMACOLOG Y.—The most serious toxic reaction to streptomycin is deafness, which, in some cases, is permanent. Other reactions include vestibular dysfunction and vertigo, skin eruptions, renal irritation, fever, local reactions at the site of injection, nausea and vomiting, jaundice, leucopenia, agranulocytosis, eosinophilia, and circumoral paresthesia. Intrathecal administration sometimes causes sciatic pain with paraplegia and paresthesias. Persons handling the drug frequently are liable t o develop contact dermatitis [40]. Streptomycin appears in the blood in very small amounts when given p.o. o r by inhalation. After i.m. inj, streptomycin persists in the blood for about 4 hr, the p e a k concentration occurring at 1-2 hr. T h e d r u g is excreted in the urine in large quantities in the 2 hr after parenteral administration and continues t o be excreted for about 24 hr. W i t h renal impairment, the agent accumulates in the blood. As in experimental animals, streptomycin is distributed in extracellular water. A f t e r i.m. inj it is found in peritoneal fluid and aqueous and vitreous humors. It diffuses slowly into spinal fluid and pleural, synovial, and pericardial effusions [40]. CLINICAL RESULTS. — Streptomycin has been found to be of value in the following clinical conditions: Abscess, Escherichia coli, with bacteremia [40] Bed sores [40] Bronchiectasis [40] Burns [40] Chancroid [40, 41] Conjunctivitis [40] Corneal ulceration [40] Empyema [40] Empyema of gall bladder [40]

Cross references are indicated by SMALL CAPITALS

STREPTOPHAGE

[1

E n d o c a r d i t i s , a c u t e b a c t e r i a l [40] E n d o c a r d i t i s , s u b a c u t e b a c t e r i a l , d u e t o [41]: Streptococcus fecalis G r a m - n e g a t i v e bacilli E n d o p h t h a l m i t i s [40] G r a n u l o m a i n g u i n a l e [40, 4 1 , 42] H a v e r h i l l f e v e r [40] I n f e c t i o n s d u e t o [41]: Gonococci Klebsiella pneumoniae Pneumococci Streptococcus hemolyticus L a r y n g o - t r a c h e o - b r o n c h i t i s [40] M a s t o i d i t i s [40] Meningitis due to: G r a m - n e g a t i v e bacilli [40) I n f l u e n z a b a c i l l u s [40, 41] O s t e o m y e l i t i s , c h r o n i c , not d u e to s t a p h y l o c o c c i o r s t r e p t o c o c c i [40] P a n o p h t h a l m i t i s [40] P e r i t o n i t i s [40] P e r t u s s i s [40] P l a g u e , b u b o n i c a n d p n e u m o n i c [40, 41] P n e u m o n i a d u e t o Klebsiella pneumoniae (40] R a t - b i t e f e v e r d u e t o Streptobacillus moniliformis [41] S u r g e r y of b o w e l [41] S u r g e r y of l u n g [41] T u b e r c u l o s i s , s o m e f o r m s [40, 41] T u l a r e m i a [40, 41] U r i n a r y infections due to: Aerobacter aerogenes [40, 41] Alcaligenes fecalis [40] Escherichia coli [40, 41] Proteus vulgaris [40, 41] Pseudomonas aeruginosa [40, 41] W o u n d s , i n f e c t e d , v a r i o u s [40] S t r e p t o m y c i n is of little or n o v a l u e in t h e following conditions: A m e b i a s i s [40] A n t h r a x [40] B o t u l i s m [40] B r u c e l l o s i s , a c u t e [41] C h o l a n g i t i s [411 C o c c i d i o i d o s i s [40] C o l d s [40, 41] D i a r r h e a , e p i d e m i c , of n e w b o r n [401 D y s e n t e r y , b a c i l l a r y [41] E n d o c a r d i t i s , s u b a c u t e b a c t e r i a l , d u e t o [41]: A l p h a streptococci Staphylococci G a n g r e n e , gas [41] H e r p e s zoster [40] I n f e c t i o n s d u e t o [41]: Meningococci Salmonella spp. ( f o o d poisoning) Staphylococci Streptococcus fecalis I n f l u e n z a [40, 41] K e r a t o c o n j u n c t i v i t i s [40] L y m p h o g r a n u l o m a v e n e r e u m [41] M e a s l e s [40] M e l i o i d o s i s [40] M o n o n u c l e o s i s , i n f e c t i o u s [40] O s t e o a r t h r i t i s [40] Otitis, c h r o n i c , e x t e r n a l [40] P a r a t y p h o i d i n f e c t i o n s [401 P e r t u s s i s [41] P h a r y n g i t i s , a c u t e [40] P n e u m o n i a , p r i m a r y atypical [40, 41] P s i t t a c o s i s [41] R a t - b i t e f e v e r d u e t o Spirillum minus [41]

] R h e u m a t i c f e v e r [40, 41] R h e u m a t o i d a r t h r i t i s [40] Rickettsial diseases [41] SyphUis [41] T y p h o i d [41] U r i n a r y i n f e c t i o n s d u e to: Streptococcus fecalis [41] V i r a l a n d o t h e r n o n b a c t e r i a l c a u s e s [40] Y a w s [41] See [1] S c h a t z et al., 1944; [2] J o h n s t o n e a n d W a k s m a n , 1947; [3] J o h n s t o n e a n d W a k s m a n , 1948; [4] V a n d e r B r o o k et al., 1946; [5] W a k s m a n , Bugie, a n d S c h a u , 1944; [6] R e g n a et al., 1946; [7] D e n k e l w a t e r et al., 1945; [8] K u e h l , P e c k , H o f f h i n e , a n d F o l k e r s , 1948; [9J B a r t z et al., 1946; [10] P a i n e a n d F i n l a n d , 1948; [11] H o b b y a n d D o u g h e r t y , 1948; [12] K u s h n i c k el al., 1947; [13] V e n n e s l a n d et al., 1947; [14] K o l m e r a n d R u l e , 1948; [15] N i c h ols, 1948; [16] A n d e r s o n a n d C h i n n , 1947; [17] Bliss a n d T o d d , 1949b; [18] I C a v a n a u g h , 1947b; [19] Foley, 1947; [20] Y o w a n d S p i n k , 1949; [21] A l e x a n d e r et al., 1949; [22] J o n e s , 1945; [23] A n d e r s o n et al., 1946; [24] C h i n n a n d M o l l a r i , 1949; [25] C a m p b e l l a n d S a s l a w , 1949; [26] Reilly et al., 1945; [27] W a k s m a n , F r a n k e l , a n d G r a e s s l e , 1949; [28] M o l i t o r et al., 1946; [29] M o l i t o r , 1947; [30] M o o r e et al., 1946; [31] S t e v e n s o n et al, 1947; [32] P i c k , 1947; [33] M a r s h a l l , 1948; [34] S m i t h a n d R o b i n s o n , 1945; [35] H e w i t t , 1948; [36] J a w e t z , 1948; [37] F i s k e n a n d G r u h z i t , 1946; [38] A d a m s et al., 1949; [39] W o o d y a n d A v e r y , 1948; [40] L o n g , 1948; [41] L o n g et al., 1949; [42] G r e e n b l a t t et al., 1949; [43] Bliss a n d W a r t h , 1950; [44] F i s h e r , 1950. F o r a d d i t i o n a l l i t e r a t u r e see F l o r e y et al., 1949; W a k s m a n , 1949. See

also

PASTEURELLA

MULTOCIDA.

S t r e p t o p h a g e , as test o r g a n i s m in vitro, PERGILLUS

see AS-

spp.

Streptosolen j a m e s o n i l , a h i g h e r p l a n t , a q u e o u s e x t r a c t s of w h i c h are ineffective in vitro a g a i n s t Staphylococcus aureus a n d Escherichia coli. See O s b o r n , 1943. streptostasin, a n a n t i b i o t i c s u b s t a n c e p r o d u c e d by c e r t a i n b e t a - h e m o l y t i c s t r e p t o c o c c i . It inhibits o t h e r s t r e p t o c o c c i b u t n o t Bacillus anthracis, Escherichia coli, Salmonella typhi, or Staphylococcus aureus. See S h e r w o o d et al., 1949. streptothricin, a n a n t i b i o t i c s u b s t a n c e d e r i v e d f r o m c u l t u r e filtrates of Actinomyces lavendulae. It is isolated by a d j u s t i n g t h e m e d i u m t o p H 3.5, filtering, n e u t r a l i z i n g t h e filtrate, a d s o r b i n g o n c h a r c o a l , e l u t i n g with d i l u t e m i n e r a l acid, n e u t r a l i z i n g , e v a p o r a t i n g in vacuo, e x t r a c t i n g the residue with a b s o l u t e e t h a n o l , filtering, and e v a p o r a t i n g [1]. A m o r e r e c e n t m e t h o d involves c h a r c o a l a d s o r p t i o n , e l u t i o n w i t h f o r m i c acid, p r e c i p i t a t i o n with picric a c i d , c o n version to t h e h y d r o c h l o r i d e , a n d c h r o m a t o g r a p h y [2], S t r e p t o t h r i c i n is s o l u b l e in w a t e r a n d dilute m i n e r a l a c i d s a n d i n s o l u b l e in e t h e r , p e t r o l e u m e t h e r , a n d c h l o r o f o r m [1], It is inactivated by c o n c e n t r a t e d m i n e r a l a c i d s [1] b u t u n a f f e c t e d by cysteine [3], b l o o d [4], s e r u m [4], p e p t o n e [4], o r t h e v i t a m i n B c o m plex [4], T h e activity is also u n a f f e c t e d b y boiling f o r 15 m i n [1]. T h e unit of s t r e p t o t h r i c i n is " t h e m i n i m u m q u a n t i t y of d r u g w h i c h w h e n a d d e d to 1 cc of n u t r i e n t b r o t h will i n h i b i t a given strain of E. coli" [5]. It is b a c t e r i c i d a l as well as b a c t e r i o s t a t i c [1],

C r o s s r e f e r e n c e s a i e i n d i c a t e d by SMALL CAPITALS

STREPTOTHRICIN

[287] SPECTRUM.—A crude preparation of streptothricin inhibits the following microrganisms in the concentrations stated [1]: Inhibiting Organism concentration mg/cc Actinomyces albus 0.03 Actinomyces lavendulae 0.3 Actinomyces violaceus ruber 0.03 Aerobacter aerogenes 0.03 Azotobacter agile 0.003 Azotobacler chroococcum 0.03 Azotobacter indicum 0.03 Azotobacter \inelandii 0.003 Bacillus cereus not inhibited at 0.3 Bacillus macerans not inhibited at 0.3 Bacillus megatherium 0.01 Bacillus mycoides not inhibited at 0.3 Bacillus polymyxa 0.1 Bacillus subtilis 0.003 Brucella abortus 0.01 Clostridium butyricum not inhibited at 0.3 Escherichia coli 0.01 Hemophilus influenzae 0.003 Hemophilus suis 0.03 Lactobacillus casei 0.03 Micrococcus lysodeikticus 0.03 Mycobacterium phlei 0.03 Pasteurella pseudotuberculosis 0.03 Pseudomonas fluorescens not inhibited at 0.3 Salmonella abortisoequina 0.03 Salmonella choleraesuis 0.03 Salmonella schottmuelleri 0.03 Salmonella typhimurium 0.03 Sarcina lutea 0.01 Serratia marcescens 0.3 Shigella gallinarum 0.01 Staphylococcus muscae 0.03 Purer preparations of streptothricin have the following spectrum: Inhibiting concentration Organism units/cc Aerobacter aerogenes 256 [4, 5] Bacillus mycoides 1,024 [4, 5j Bacillus subtilis 32 [4, 5] Clostridium novvi 210 [4] Clostridium septicus 540 [4] Clostridium sordelli more than 1,080 [4] Clostridium tetani more than 1,080 [4] Clostridium welchii more than 855 [4] Diplococcus pneumoniae 32 [4, 5] Escherichia coli 16 [4, 5] Mycobacterium leprae 0.1-1.0 [6] Mycobacterium smegma 0.1 - 1.0 [6] Mycobacterium tuberculosis avium 0.1-1.0 [6] Mycobacterium tuberculosis hominis 0.1-1.0 [6] Neisseria meningitidis 256 [4, 5] Pasteurella lepiseptica 32 [4, 5] Proteus vulgaris 512 [4, 5] Pseudomonas aeruginosa 256 [4, 5] Salmonella aertrycke 16 [4, 5] Salmonella enteritidis 64 ¡4, 5]

Inhibition concentration Organism units/cc Salmonella schottmuelleri 16(4,5] Salmonella typhi 4 [4, 5] Sarcina lutea 256 [4, 5] Shigella flexneri 32 [4, 5] Shigella sonnei 128 [4,5] Staphylococcus aureus 16- 128 [4, 5] Streptococcus hemolyticus 32-256 [4,5] Streptococcus lactis 1,024 [4], more than 1,024 [5] Streptococcus viridans 1,024 [4], more than 1,024 [5] Another spectrum for this substance is also reported [7]: Inhibiting concentration in Organism micrograms/cc Bacillus mycoides 100 Bacillus subtilis 0.8 Escherichia coli 0.3 Klebsiella pneumoniae 0.1 Mycobacterium phlei 7 Mycobacterium smegma 14 Photobacterium fischeri 20 Pseudomonas aeruginosa 2 Staphylococcus aureus 0.1 The antifungal activity of streptothricin is as follows [8]: Activity of agent in Fungus units/gm Aspergillus clavatus less than 60 Candida albicans less than 60 Cryptococcus neoformans 12,000 Dematium sp. 6,000 Fusarium sp. 9,000 Pénicillium luteum purpurogenum 3,000 Trichophyton mentagrophytes 4,500 Streptothricin also inactivates a number of bacteriophages [9]. TOXICITY.—The maximum tolerated dose in mice is more than 2,000 mg/kg p.o., more than 1,000 mg/kg s.c., 3,000 mg/kg i.p„ and 1,000 mg/kg i.v. [10]. It is also reported that 60,000 units/kg i.v. kills 20% of experimental mice and 500,000 units/kg kills 100%. By the s.c. route, 125,000 units/kg kills 30% and 250,000 units/kg kills 100%. Oral doses of 750,000 units/ kg are lethal for only 30% [4]. In rabbits i.v. inj of 5,000-20,000 units/kg twice a day results in destruction of the stomach lining, mottling of liver and kidneys, and ultimate death of the animal. Oral administration of larger quantities has the same effect. Application of the drug to scarified skin also produces the same effect, but topical application on unbroken skin is without toxic effect. Intradermal inj of 2,000-6,000 units results in hemorrhagic areas [11]. When streptothricin is given to chicks at the rate of 5,000 units/100 gm of purified diet there are no deleterious results. Twice that amount, however, is toxic [12]. EXPERIMENTAL CLINICAL RESULTS.— In mice infected with Salm. schottmuelleri, single doses of 2,500-5,000 units/kg i.v. or s.c. protect the majority of animals. Somewhat smaller amounts suffice when the agent is administered i.p. [5]. Single s.c. doses of 100-200 units/mouse are effective against infections due to E. coli, Salm. typhi, Salm. aertrycke, and

Cross references are indicated by

SMALL CAPITALS

STREPTOTHRICIN VI

[2M]

Salm, schottmuelleri and prolong life in mice infected with Pr. vulgaris and Ps. aeruginosa [4J. Streptothricin is also effective in the treatment of Strep, hemolyticus [4] and Shig. shigae [3] infections in mice but ineffective against Staph, aureus [4, S], Dipl. pneumoniae [4, 5], epidemic inflluenza [4,5], and Trypanosoma equiperdum [4,5] infections. Approximately fifteen to thirty times the parenteral dose is required to obtain the same results with oral administration [4, 5], Oral administration of 30,000-60,000 units kg per day in mice causes rapid reduction in the number of coliform and non-lactose-fermenting microorganisms in the feces [13]. Similarly, oral administration reduces the number of coliform organisms in the caecal contents of chicks [12], See [1] Waksman and Woodruff, 1942; [2] Peck, Walti, Graber, Flynn, Hoffhine, Allfrey, and Folkers, 1946; [3] Denkelwater et al., 1945; [4] Robinson and Smith, 1944; [5] Robinson et al., 1944; [6] Woodruff and Foster, 1944; [7] Kavanaugh, 1947b; [8] Reilly et al., 1945; [9] Jones, 1945; [10] Waksman, 1945; [11] Stanley, 1946; [12] Moore et al., 1946; [13] Smith and Robinson, 1945. streptothricin VI, an antibiotic substance produced by a strain of Streptomyces la vcndulae. It is isolated by adjusting the culture filtrate to pH 2-2.5, stirring with Darco G-60, filtering, and adsorbing the active fraction on norit at pH 7-7.3. After elution, the eluate is evaporated, the residue dissolved in methanol, and the active substance precipitated with acetone. Streptothricin VI is soluble in water and methanol and insoluble in ether, acetone, and ethanol. It is stable at acid and neutral pH at 5°-25°C. The activity passes through sintered glass filters but is held back to greater or less extent by Mandler "W" or Seitz "EK" filters. The substance is dialyzable and is not inactivated by cysteine. The unit is the amount which is equivalent in potency to one microgram of streptomycin. SPECTRUM.—Resistant strains of Escherichia coli may be developed by exposing sensitive strains to increasing concentrations of the agent. There is a synergistic action of this material and streptomycin against mycobacteria. The following microorganisms are inhibited in vitro in the concentrations shown: Inhibitory concentration Organism units'cc Bacillus cereus 100 100 Bacillus mycoides Bacillus subtiiis 0.3 Candida albicans more than 150 Escherichia coli 1 Mycobacterium 607 0.7 Mycobacterium butyricum 1 Mycobacterium phlei 0.2 Mycobacterium tuberculosis 20 Mycobacterium tuberculosis avium 2 Proteus vulgaris 0.3 Pseudomonas jluorescens 90 Serratia marcescens 90 Staphylococcus aureus 2 Trichophyton mentagrophytes more than 150 TOXICITY. — Parenteral administration of 750 units/20 gm mouse is without effect; 3,000 units causes delayed toxic effects.

EXPERIMENTAL CLINICAL RESULTS. —Streptothricin VI is efficacious in the treatment of Salmonella schottmuelleri infections in mice. See Hutchison et al., 1949. Streptothrix, a genus of organisms of the group Chlamydobacteriaceae, some members of which in vitro lyse Staphylococcus aureus, Staph, albus, Sarcina, and Bacillus megatherium. "Extracts" of the organisms and the washed mold "dissolve" streptococci and pneumococci. Escherichia coli, Salmonella typhi, Salm. paratyphi. Salin, enteritidis, Salm, aetrycke, B. subtiiis, Pseudomonas aeruginosa, and Ps. jluorescens are not affectcd by any of these conditions. See Welsch, 1937a. Strobilanthes isophyllus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Stropharia aeruginosa, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Stropharia albocyanea, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Stropharia caput-medusae, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946a. Stropharia coronilla, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947c. Stropharia depillata, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Stropharia mammillata, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Stropharia merdaria, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Stropharia semiglobata, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Extracts of the sporophores of this fungus also are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2]. See [1] Wilkins, 1947c; [2] Wilkins and Harris, 1944d. Stropharia squamosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Stropharia stercoraria, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Strophostyles helvola, a higher plant, extracts of which are ineffective in vitro against Bacillus subtiiis and Escherichia coli. See Sanders et al., 1945. Strumpfia maritima, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Strychnos brasiliensis. a higher plant, extracts of the bark of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947.

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

SUBTILEN

[289] Strychnos fendleri. a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Strychnos panicula. a higher plant, concentrated aqueous extracts of the Chinese drug p r e p a r e d f r o m the stem of which are ineffective in viiro against Staphylococcus aureus and Escherichia coli. See Gaw and Wang, 1949. Strychnos pseudo-quina, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Stuartia monodelpha, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. styes, clinical, see B A C I T R A C I N . Stylidium graminifolium, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Stylogyne laevigata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Stylophorum diphyllum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Styrax officinalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Stysanus stemonitls, a fungus which is ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1942. Suaeda fruticosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. subtenolin, an antibiotic produced by Bacillus subtilis [1]. It is isolated f r o m the culture filtrate by adsorption on charcoal, elution with methanol, concentration in vacuo, precipitation with butanone, extraction of the active fraction into methanol, and evaporation to dryness in vacuo. The product is a light-yellow powder containing as m u c h as 1,600 dilution u n i t s / m g . Subtenolin is soluble in water, ethylene glycol, and 9 5 % methanol, and is insoluble in acetone, b u t a n o n e , ether, and 9 5 % ethanol. It is thermostable, no loss of activity occurring after autoclaving in aqueous solution f o r 15 min at 15 lb pressure. The activity is also unaffected by standing at rm. temp, f o r 18 hr at p H 2. T h e active material dialyzes through cellophane membranes [2], Whole, defibrinated rabbit blood inactivates subtenolin; horse and rabbit serums, however, have no effect. The activity of subtenolin is reduced by overnight incubation. T h e unit of subtenolin is the least a m o u n t in 1 cc which completely inhibits the growth of Staphylococcus aureus in 5 hr [1], SPECTRUM.—Subtenolin is inhibitory vitro f o r the following organisms [1]: Aerobacter aerotienes Bacillus anthracis Clostridium fallax Clostridium histolyticum Clostridium novyi Clostridium oedematiens maligni Clostridium perfringens Clostridium tertium

in

Diplococcus pneumoniae Escherichia coli Klebsiella pneumoniae Micrococcus conglomerate Micrococcus lysodeikticus Neisseria gonorrhoeae Pasteurella sp. Pasteurella pestis Pseudomonas aeruginosa Salmonella enteritidis schottmuelleri Salmonella Salmonella typhi Salmonella typhimurium Serratia marcescens Staphylococcus albus Staphylococcus aureus Streptococcus sp. Streptococcus pyogenes Subtenolin is ineffective in vitro against the following organisms [1]: Bacillus subtilis Bacillus subtilis (subtenolin-producing strain) Brucella abortus Brucella ntelitensis Brucella suis Salmonella paratyphi TOXICITY AND PHARMACOLOGY.— T h e i.p. LDr.o for 17-23 gm mice of a sample of subtenolin assaying 1,000 u n i t s / m g is 30-60 mg. Subtenolin appears in the urine 15 min after inj and may continue to be excreted f o r as long as 10 hr. Thirty to fifty percent of the total i.p. dose may be recovered f r o m the urine [1]. See [1] Hirschhorn et al., 1948; [2] Howell and Tauber, 1948. subtilin, an antibiotic substance derived f r o m a strain of Bacillus subtilis. It is isolated by adjusting whole cultures of the producing organism to p H 4.7, centrifuging, desiccating the residue, extracting with ethanol, and precipitating with sodium chloride solution. Subtilin loses activity o n storage in a v a c u u m desiccator at 5 ° C . It is also inactivated by heat and by light [1]. Sodium chloride, however, does not affect the activity of this agent. BAL (2,3-dimercaptopropanol) increases t h e activity of subtilin against mycobacteria in vitro but has n o apparent effect o n its ability to inhibit Micrococcus lysodeikticus [2]. A unit of subtilin is the " a m o u n t present in 1 cc of the highest dilution (expressed in milligrams) capable of killing Staph, aureus in 10 m i n at 3 7 C C . " [3], SPECTRUM.—The following bacteria inhibited in vitro by subtilin: Alcaligenes viscosus [4] Bacillus anthracis [4] Bacillus cereus [4] Bacillus megatherium [4] Corynebacterium diphtheriae [4] Diplococcus pneumoniae [4] Gaffkya tetragena [4] Lactobacillus casei [ 1 , 4 ] Lactobacillus delbruckii [4] Lactobacillus fermenti [4] Lactobacillus pentosus [4] Micrococcus conglomeratus [1] Micrococcus lysodeikticus [2] Micrococcus ureae [4] Mycobacterium sp. [2] Mycobacterium phlei [4]

Cross references are indicated by SMALL CAPITALS

are

SUBTIL IN C

[MO]

Mycobacterium smegma [4] Mycobacterium tuberculosis [4] Mycobacterium tuberculosis bovis [2] Mycobacterium tuberculosis hominis [2] Neisseria catarrhalis [4] Neisseria gonorrhoeae [4] Rhodococcus roseus [4] Sarcina lutea [4] Sarcina ureae [4] Staphylococcus aureus [1, 3, 4] Staphylococcus citreus [4] Streptococcus fecalis [4] Streptococcus Iactis [4] Streptococcus pyogenes [4] Streptococcus viridans [1] The following organisms are resistant to the action of subtilin in vitro: Aerobacter aerogenes [4] Alcaligenes fecalis [4] Brucella abortus [4] Brucella suis [4] Escherichia coli [4] Escherichia coli communior [4] Klebsiella pneumoniae [4] Pasteurella avicida [4] Proteus vulgaris [4] Proteus X-19 [4] Pseudomonas aeruginosa [4] Pseudomonas fluorescens [4] Salmonella paratyphi [4] Salmonella schottmuelleri [4] Salmonella typhi [1,4] Serratia marcescens [4] Shigella alkalescens [4] Shigella dysenteriae [4] Shigella paradyscnteriae [4] Shigella sonnei [4] Vibrio comma [4] The following fungi are inhibited in vitro at 1:1,000 [4]: Actinomyces sp Actinomyces asteroides Actinomyces pelletieri Nocardia mexicana The following fungi are not affected by subtilin in dilutions of 1:1,000 [4]: Actinomyces sp. Candida albicans Cryptococcus neoformans Pénicillium notatum Sporotrichum schenckii Trichophyton gypseum TOXICITY.—A concentration of 1:500 is required to kill fragments of embryonic chick heart in 10 min at 37°C. [31. In the dosage levels employed, subtilin has been nontoxic to mice and guinea pigs (see below) [5, 6]. EXPERIMENTAL CLINICAL RESULTS. —Guinea pigs survive Bacillus anthracis infections when given 11 i.p. doses of 2 mg each at 3-hr intervals, followed by 3.3 mg three times a day for 8 days [6]. Mice are protected from Diplococcus pneumoniae infections by 8 i.p. injs of 0.5 mg each over a period of 36 hr [5]. In both instances subtilin treatment may safely be postponed for 9 hr after infection [5, 6], Similar results have been obtained with Streptococcus pyogenes infections in mice [7]. Subtilin is ineffective against syphilis in rabbits [8] and against tuberculosis in guinea pigs [91.

IN VIVO ACTIVITY AGAINST PLANT PATHOGENS—Treating barley seeds with subtilin reduces the incidence of Xanthomonas translucens f. sp. cerealis infections [10], See [1] Jansen and Hirschmann, 1944; [2] Anderson and Chin, 1947; [3] Salle and Jann, 1946a; [4] Salle and Jann, 1945; [5] Salle and Jann, 1946b; [6] Salle and Jann, 1946c; [7] Salle and Jann, 1946d; [8] Eagle et al„ 1948; [9] Steenken and Wolinsky, 1949; [10] Goodman and Henry, 1947. snbtilhi C, an antibiotic obtained from one of the strains of Bacillus subtilis which produces subtilin. It is isolated by disintegrating the cells in alcoholic suspension with glass beads, diluting, and adjusting to pH 2.3. The active concentrate is an amorphous powder. The substance, which appears to be a polypeptide, is destroyed by sunlight and by alkali. It is differentiated from subtilin by chemical tests. SPECTRUM.—Gram-negative organisms are not affected by concentrations of 1:2,000. Fifty percent inhibition of the following organisms is effected by the concentrations shown: Inhibitory Organism concentration Corynebacterium xerosis 1:5,000,000 Lactobacillus helveticus 1:2,400,000 Micrococcus conglomerate 1:600,000 Mycobacterium sp. (from butter) 1:300,000 Mycobacterium phlei 1:60,000 Sarcina lutea 1:10,000,000 Staphylococcus aureus 1:80,000 to 1:8,000,000 See Hassall, 1948. subtilysine, an antibiotic isolated from Bacillus subtilis. It is effective in vitro against Escherichia coli, Clostridium septicum, CI. oedematiens, Salmonella enteritidis, Brucella abortus, and Pasteurella. It is ineffective against streptococci and staphylococci. The compound withstands heating at 56 °C. for one hour in aqueous solution; it is destroyed in one-half hour at 80 °C. At rm. temp, it is stable for 8 mo. Three cc. of subtilysine solution, when injected 45 min after inoculation of guinea pigs with CI. septicum, affords protection to the animals. It is believed to be similar to actinomycetin. See Vallee, 1945a and b. sulfactin, a crystalline, sulphur-containing antibiotic obtained from the culture fluid of a member of the Actinomyces group, probably Actinomyces roseus. It is isolated from the culture filtrate by centrifuging, adjusting to pH 7.0, and extracting with n-butanol. The butanol extract is evaporated and the residue taken up in chloroform. Purification is effected by chromatography and recrystallization from chloroform. Ten liters of crude culture yields 0.186 gm of pure white crystals containing 10.1396 moisture and 6,200,000 dilution units of activity. The m.p. is 245°-275° (corr., decomp.) and the empirical formula CssHssNn OTS* or C27H40O5N8S3. Crystalline sulfactin is soluble in chloroform, ethanol, ethyl acetate, dioxane, butanol, and methanol; and almost insoluble in water, ether, petroleum ether, and benzene [lj. The activity is not destroyed by 0.5% sodium chloride [2] or by boiling in ethanol [1] but is reduced by the presence of defibrinated normal horse serum

Cross references are indicated by SMALL CAPITALS

1291] [2]. In 309k ethanol solution, sulfactin dialyzes through a cellophane membrane without great loss of activity [1]. The dilution unit is "the smallest amount of sulfactin per ml of bacto-nutrient broth, pH 7.3, which prevents growth of Staph, aureus under the conditions of the test" [2], SPECTRUM.—The following organisms are susceptible to the action of sulfactin in vitro [2]: Bacillus anthracis Bacillus cereus Bacillus circulans Bacillus megatherium Bacillus mesentericus Bacillus mycoides Bacillus subtilis Corynebacterium diphtheriae Corynebacterium xerosis Diplococcus pneumoniae Gaffkya tetragena Micrococcus aurantiacus Micrococcus lysodeikticus Micrococcus roseus Neisseria sicca Staphylococcus aureus Streptococcus, alpha and gamma Streptococcus pyogenes Staphylococcus aureus, after seven serial transfers, develops a resistance to sulfactin over 1,100 times that of the original strain [3], The following microorganisms are not inhibited in vitro by sulfactin [2J: Aerobacter aerogenes Alcaligenes tecalis Brucella abortus Brucella melitensis Brucella suis Chromobacterium violaceum Escherichia coli Escherichia communior Escherichia neapolitania Klebsiella pneumoniae Mycobacterium smegma Neisseria catarrhalis Proteus vulgaris Pseudomonas aeruginosa Salmonella enteritidis Salmonella paratyphi Salmonella schottmuellerl Salmonella typhi Sarcina lutea Serratia marcescens Shigella dysenteriae Shigella paradysenteriae Streptococcus fecalis Trichophyton interdigitale Vibrio comma TOXICITY AND EXPERIMENTAL CLINICAL RESULTS.—The i.p. LD.-,o in 17-20 gm mice is about 2.75 mg. At autopsy, sacrificed survivors show a possible enlargement of the liver as the only pathological sign. A single i.p. inj of 1-7.5 micrograms, when given a few minutes after the infecting inoculation, suffices to protect 50% of mice from Dipl. pneumoniae infections [2], See [1] Junowicz-KochoIaty et al., 1947; [2] Morton, 1947b; [3] Morton and Perez, 1948. surgery of bowel, clinical, see PENICILLIN; STREPTOMYCIN.

surgery of lung, clinical, see PENICILLIN; STREPTOMYCIN.

SYMPLOCOS TIN CTO RIA

Suriana maritima, a higher plant, extracts of the stems of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947.

sweet potato, see IPOMOEA BATATAS.

Swertia chirata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Swertia radlata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Swietenia macrophyila, a higher plant, aqueous extracts of the commercial wood obtained from which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Bacillus anthracis. See Sanchez et al., 1948. Swietenia mahogani, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. swine pancreas, anthracidal activity, see MAMMALIAN TISSUES, EXTRACTS.

swine thymus, anthracidal activity, see MAMMALIAN TISSUES, EXTRACTS.

sycosis barbae, clinical, see PENICILLIN; TYROTHRICIN.

Symphoricarpos albus, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Symphoricarpos albus v. laevigatas, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Symphoricarpos orbicularis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2]. See [1] Osborn, 1943; [2] Hayes, 1947. Symphoricarpos racemosns, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Symphytum asperrimum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Symphytum cmicadcnm, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Symphytum officinale, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Symplocarpus foetidus, a higher plant, aqueous extracts of the flower, leaf, root, bulb, and petiole of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1J. Other extracts of this plant inhibit E. coli but not Bacillus subtilis [2]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [3], See [1] Schnell and Thayer, 1949; [2] Sanders et al., 1945; [3] Hayes, 1947. Symplocos tinctoria, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947.

Cross references are indicated by SMALL CAPITALS

SYNADENIUM GRANITI

[292]

Syasdenlnm gran til, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Syncaipia laorifolfe, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi. See Atkinson, 1949. Syncephalastrum racemoswn, a fungus, the culture medium of which is ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1943a. As test organism in vitro, see

syphilis. 1 For clinical results in the use of various antibiotics, see A U R E O M Y C I N ; C H L O R A M PHENICOL;

PENICILLIN;

STREPTOMYCIN;

TERRA-

MYCIN. 2 For experimental clinical results, see

A U R E O M Y C I N ; BACITRACIN; BORRELIDIN; C H L O R AMPHENICOL; PENICILLIN; STREPTOMYCIN; SUBTILIN; TERRAMYCIN; TYROTHRICIN.

Syringa oblata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Syringa persica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Syringa vulgaris, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

TWCHOTHECIN.

Syntherisma lschaemnm, a higher plant, aqueous extracts of the leaf and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Nrurospora crassa. See Schnell and Thayer, 1949.

T Ta Fung Tzu, Chinese name of an unidentified higher plant, concentrated aqueous extracts of the Chinese drug prepared from which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Gaw and Wang, 1949. Tabebuia sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Tabebuia argentea, a higher plant, extracts of the bark of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Tabebuia ipe, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Tabebuia pallida, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Tabenia pentaphylla, a higher plant, aqueous extracts of the commercial wood obtained from which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Bacillus anthracis. See Sanchez et al., 1948. Tabernaemontana amygdalifolia, a higher plant, extracts of some parts of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Tabemaemontana citrifolia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Tabernaemontana coronaria, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tabemaemontana beterophylla, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Tabernaemontana oppositifolia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Tacca artocarpifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tachia guianensis, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Tacsonia mixta v. quitensis, a higher plant, aqueous extracts of which are ineffective in

vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tagetes erecta, a higher plant, aqueous extracts of the seed and seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1], Other extracts of this plant are also ineffective against Staph, aureus, E. coli, and Mycobacterium tuberculosis [2], See [1] Schncll and Thayer, 1949; [2] Gottshall et al., 1949. Tagetes patula, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Talauma hodgsonil, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Talauma mexicana, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Tamarindus indica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tamarix hispida, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tamus communis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli See Osborn, 1943. Tanacetum boreale, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn. 1943. Tanacetum vulgare, a higher plant, aqueous and ether extracts of the flower, leaf, and stem of which are effective in vitro against the spores of Xeurospora crassa, while aqueous and ether extracts of the root are ineffective. Only aqueous extracts of the flower inhibit Staphylococcus aureus and only ether extracts of the stem inhibit Escherichia coli [1], Various other extracts of this plant are reported a) to inhibit Staph, aureus but not E. coli [2, 3] and b) to be ineffective against Staph, aureus [4], E. coli [4. 5], Mycobacterium tuberculosis [4], and Bacillus subtilis [5], Sec [1] Schnell and

Cross references are indicated by

SMALL CAPITALS

TERRAMYCIN

[293 ]

Thayer, 1949; [2] Osborn, 1943; [3] Carlson, Douglas, and Robertson, 1948; [4] Gottshall ct al., 1949; I?] Sanders ct al., 194?. Tanacetum >ulgare v. crispum, a higher plant, aqueous extracts of which are effective in \iiro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Taraktogenos kurzii, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Taraxacum mongolicum, a higher plant, concentrated aqueous extracts of the Chinese drug prepared from the leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Gaw and Wang, 1949. Taraxacum officinale, a higher plant, aqueous and ether extracts of the flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1], Other aqueous extracts of this plant are also ineffective against Staph, aureus and E. coli [2]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth when tested in vitro against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumejaciens [3]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943; [3] Hayes, 1947. Taraxacum palustre, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Tarchochanthus camphorstus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. tardin, a noncrystalline antibiotic produced by the fungus Penicillium tardum. It is extracted from the culture filtrate by adjusting to pH 7, shaking with amyl acetate, distilling, dissolving the residue in benzene, and passing this solution through an aluminum oxide column at pH 5. The product is a pale-yellow oil with the proposed formula C11H1DO3. It is stable in the pH range 2-8 and is laevorotatory in alcohol. Tardin is slightly soluble in water and in warm hexane and is soluble in alcohol, acetone, ether, benzene, and amyl acetate. It is inactivated by the presence of serum. SPECTRUM.—Corynebacterium diphtheriae gravis, Coryne. xerosis, Salmonella enteriiidis, Staphylococcus aureus, and Streptococcus viridans are inhibited by tardin, but Pseudomonas aeruginosa and Escherichia coli are not affected by concentrations of 1:1,000. The following pathogenic fungi are inhibited by 1:5,000; Sabouraudites audouini, S. lanosus, Trichophyton equinus, and T. sabouraudii. Trichophyton lacticolor, T. tonsurans, and Endomycopsis albicans are not affected by the same concentration. None of the fungi listed is inhibited at 1:20,000. TOXICITY— Leucocytes are killed in 30 min in a 1:2,000 solution of tardin; 1:16,000 is without effect. In 20 gm mice single injs of 0.8 mg i.v. or 2.5 mg s.c. produce only transient illness; larger doses cannot be tried because of poor solubility. In the isolated guineapig uterus solutions of 1:25,000 cause irreversible increase in contractions, followed by

stoppage of contractions. Intravenous inj of 30 mg causes a transitory fall in b.p. in a 2.5 kg cat. See Borodin, et al., 1947. Taxus baccata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Osborn, 1943. Taxus canadensis, a higher plant, extracts of the fruit of which in vitro inhibit Staphylococcus aureus, Escherichia coli, and Erwinia carotovora, but do not inhibit Phytomonas tumefaciens. Extracts of the leaves are inactive against all four test organisms. See Hayes, 1947. Taxus cuspidata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. tea. Various extracts of tea inhibit the multiplication of influenza virus in embryonated eggs. Sec Green, 1949. tears, see

LYSOZYME.

Tecoma flavescens, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Tecoma pentapbylla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tecomomaria capensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tectona grandls, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tephrosia virginiana, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Terminalia chebuba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ternstroemia japonica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. terramycin, a crystalline antibiotic produced by Streptomyces rimosus n. sp. Terramycin is an amphoteric compound which analyzes as follows: C, 53.05; H, 5.91; N, 5.64; O, 35.4. The m.p. is 185°C. (decomp.). The crystals occur in several forms depending on the method of crystallization used. The agent is soluble in water, methanol, ethanol, acetone, and propylene glycol and is insoluble in ether and petroleum ether. It is stable for long periods at pH 2-5 in aqueous solution at rm. temp. The hydrochloride and the sodium salt, both crystalline compounds, have been obtained. SPECTRUM—The following bacteria are completely inhibited in vitro by terramycin: Inhibiting concentration terramycin hydrochloride expressed as micrograms/cc Bacteria terramycin equivalent Aerobacter aero genes 1.0 Bacillus subtilis 3.1 Brucella bronchisepticus 3.0 Escherichia coli 4.0

Cross references are indicated by SMALL CAPITALS

TERREIC ACID

1294]

Inhibiting concentration terramycin hydrochloride expressed as micrograms' cc Bacteria terramycin equivalent Klebsiella pneumoniae 3.0 Proleus sp. more than 1,000 Pseudomonas aeruginosa 100 Salmonella paratyphi 1.0 Salmonella pullorum 10.0 Salmonella schottmuelleri 1.0 Salmonella typhi 3.0 Shigella paradysenteriae 1.0 Staphylococcus albus 1.0 Staphylococcus aureus 1.0 TOXICITY.—The i.v. LDo in mice for the hydrochloride is equivalent to 103 m g / k g of the amphoteric compound. The i.v. LDso is 192 mg/kg. EXPERIMENTAL CLINICAL RESULTS. —Terramycin is effective both orally and pare n t e r a l ^ in the treatment of mice infected with Diplococcus pneumoniae, Kleb, pneumoniae, Salm. typhi, and Streptococcus hemolyticus. It may also be effective against rickettsiae and the influenza virus in chick embryos [1]. ABSORPTION AND EXCRETION. — Determinations of absorption and excretion of terramycin in human beings indicate that this drug is readily absorbed after oral administration. The maximum serum concentrations attained after oral doses of 50 m g / k g were 12 to 16 micrograms/ml. Reasonably high serum concentrations were maintained with daily doses of 50-100 m g / k g by mouth. Measurable concentrations were obtained in the cerebrospinal fluid and in other body fluids when sufficiently large doses had been administered. High concentrations of drug were attained in the urine. See [1] Finlay et al., 1950; [2] Werner et al., 1950. For literature on spectra, absorption, excretion, toxicity, and laboratory and clinical experimental indications see Hendricks et al., 1950; Hobby et al., 1950a; Hobby et al., 1950b; King et al., 1950; Werner et al., 1950; for some of the reports presented at the Conference on Terramycin (June, 1950), see Herrell et al., 1950; Kneeland, 1950 (atypical pneumonia); Knight, 1950 (brucellosis); P'an, 1950; Rose, 1950 (rickettsiapox); Smadel et al., 1950 (typhus); Welch, 1950; Woodward et al., 1950 (rickettsial and bacterial infect i o n s ) . See also PASTEURELLA MULTOCIDA.

terrelc acid, an antibiotic isolated f r o m Aspergillus terreus which is effective in vitro against Staphylococcus aureus, Escherichia coli, Pseudomonas pyocyanea. Streptococcus hemolyticus, and Salmonella typhi. On crystallization it assumes the form of colorless plates. Its m.p. is 120°-121°C. It is very soluble in ether, benzene, ethyl alcohol, and acetone, and is slightly soluble in water and in hexane. It is stable at p H 2 at 37°C., but not on boiling. At p H 10 all activity is lost on incubating at 37 °C. f o r 3 hr. The empirical formula is CTHSO-I. TOXICITY.—Intravenous inj of 2 mg of the sodium salt kills a 20 gm mouse in about 2 hr; 0.75 mg is without effect. Intermediate doses are fatal in several hours. A concentration of 1:2,000 kills human leucocytes at once; at

1:16,000 leucocytes are killed within an hour. Only at 1:250,000 is the effect of terreic acid solution the same as that of the control solution. The vapor causes irritation of the nose and throat. The skin is stained yellow and does not lose its color until the epithelium wears off. See Pausacker et al., 1947, unpublished. Tessaria integrifolia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Tcstudtnaria elephantlpes, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. tetanus, clinical, see PENICILLIN. Tetrahymena geleU, a Protozoon, lysates of which are effective m vitro against Mycobacterium phlei and Myco, tuberculosis hominis but not against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Photobacterium fischeri. A sodium hydroxide extract of the ether-soluble fraction of the lysates inhibits Myco, tuberculosis hominis, Myco, phlei, pneumococci, Streptococcus pyogenes, Strep, viridans, and Staph, aureus and is ineffective against E. coli, Salmonella enteritidis, and Shigella dysenteriae. Sodium carbonate extracts of the ether-soluble portion and sodium salts of the hexane-soluble portion are less active. All the extracts are inactivated by blood and serum and none has any therapeutic effect against Myco, tuberculosis and pneumococci in vivo. I n mice 14 mg injs of the sodium hydroxide extract of the ether-soluble fraction i.p. or s.c. are nonfatal; 7 mg i.v. is fatal. See McKee et al., 1947. As test organism in vitro, s e e BORRELIDIN; CHLORAMPHENICOL; P R O T O A N E M O N I N : R A N U N C U L U S OCCIDENTAL«.

Tetrahymena vorax, a Protozoon, lysates of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Mycobacterium phlei, and Myco, tuberculosis hominis. See McKee et al., 1947. Tetranema mexlcanom, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tetratheca thymifolia, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Tencrhim b o t r j s , a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Teucrhim canadense, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Teucrium fruticans, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Teacrhim scorodonia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thalictnim alpinum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. T h a l k t n i m aqallegifolhim, a higher plant, aqueous extracts of which are ineffective in vitro

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[295] against Staphylococcus aureus and Escherichia coli. See Obborn. 1943. Thalictrum dloicum, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erninia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Thalictrum dipterocarpum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbora, 1943. Thalictrum flavtim, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thalictrum glaucum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thamnldlum cbactociadioides, a fungus, the culture medium of which is ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1943a. Thamnidhim elegans, a fungus, the culture medium of which is ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa [lj. In another series of tests in vitro this fungus is reported effective against Mucor sp. [2J. See [1] Wilkins and Harris, 1943a; [2] Schmidt, 1925, As test organism in vitro, see TRICHOTHECIN. Thamnolia vermicularis, a lichen, extracts of which are effective in vitro against Alcaligenes jecalis and Staphylococcus aureus a n d / o r Bacillus subtilis. See Burkholder and Evans, 1945. Thea sinensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Theiier's Intestinal virus, experimental infections, see CHLORAMPHENICOL.

Thelephora terrestris, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Theobroma cacao, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Theophrasta minor, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thermopsis fabacea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thespesia lampas, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thespesia populnea, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Thevetia nereifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thevetia ovata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947.

THUJA PLICATA

Thevetia peruviana, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Thielavia basicola, as test organism in vitro, s e e BACILLUS MESENTERICUS VULGATUS.

Thielaviopsis spp., as test organisms in

vitro,

s e e BACILLUS s p .

Thlmus serptllom, see PHYTONCIDES. Thomasia quercifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thriptomene saxlcola, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi. See Atkinson, 1949. Thuja occidentalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thuja plicata, a tree (Western Red Cedar), from the heartwood of which are obtained two or more antibiotic substances. A decoction prepared by simmering fresh sawdust in water for 48 hr inhibits the following organisms in concentrations of 0.57-1.62 mg total solids/cc [I]: SPECTRUM.— Alcaligenes jecalis Bacillus suhtilis Candida albicans Corynebacterium xerosis Cryptococcus neoformans Epidermophyton floccosum Escherichia coli Klebsiella pneumoniae Microsporum audouini Microsporum felineum Mycobacterium tuberculosis Proteus OX-19 Proteus vulgaris Pseudomonas aeruginosa Salmonella paratyphi Salmonella schottmuelleri Salmonella typhi Shigella dysenteriae Shigella paradysenteriae Shigella sonnei Staphylococcus albus Staphylococcus aureus Streptococcus fecalis Streptococcus hemolyticus Streptococcus viridans Trichophyton gypseum Trichophyton purpureum Mycobacterium smegma is not affected by 1.15 mg/cc. Thuja plicata is also reported to be effective in vitro against Polystictus versicolor, Poria incrassata, and Fomes annosus, the last in a concentration of .01% [3]. The extract is inactivated by cysteine, blood, and serum but is unaffected by urine and gastric residue. The active principle dialyzes through a cellophane membrane. Boiling to dryness does not decrease potency, while heating to 200 °C. in sealed vials for 10 min reduces activity only 30%. The activity also withstands considerable changes in pH. TOXICITY.—Mice maintained on drinking water containing 2.3 mg/cc and mice given single s.c. injs of 1.4 mg show no signs of ill-

Cross r e f e r e n c e s a r e indicated by SMALL CAPITALS

[2*>]

THUNBERGIA AFFINIS

ness. In rabbits 2.3 mg i.v. twice a day for 3 days has no effect. EXPERIMENTAL CLINICAL RESULTS. —Systemic infections in mice due to pneumococcus, Strep, hemolyticus, Candida albicans, or Cryptococcus hominis are not benefited by the extract. When given p.o., it does not change or reduce the bacterial flora in the ceca of mice. However, some of the active material is excreted in the urine of mice and rabbits previously given injs of the extract [1]. Also reported from the heartwood of this tree are four isomeric substances, at least two of which have antibiotic properties. They are [2]: Dehydroperillic acid, m.p. 82°C.; suggested formula:

OH

C

CHs CHj a thujaplicin, m.p. 34°C.; suggested formula:

Thunbergia erects, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thymus serpyllum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thymus vulgaris, a higher plant, aqueous extracts of the seed of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. thyroid, a polypeptide extracted from hog thyroid which causes agglutination of Staphylococcus aureus, Escherichia coli, Bacillus megatherium, and Streptococcus hemolyticus. The bacteria-polypeptide combination is resistant to washing and is capable of combining with ribonucleic acid. See Bloom and Blake, 1948. thyroiditis, clinical, see AUREOMYCIN. Thyrsacanthus lemairensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thyrsacanthus rutilaos, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tiareiia cordifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ttbonchina semidecandra, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. tick-bite fever, experimental, see AUREOMYCIN; CHLORAMPHENICOL;

ß thujaplicin, m.p. 52°C.; suggested formula:

CHs CH \:Hs w

H

y thujaplicin, m.p. 82°C.; suggested formula: H

CHs — C — CHs I

H See [1] Southam, 1946; [2] Erdtman and Gripenberg, 1948; [3] Cartwright, 1941. Thunbergia affinis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Thunbergia aiata, a higher plant, aqueous extracts of the seed, flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949.

TERRAMYCIN.

Tigridium pavonia, a higher plant, aqueous extracts of the flower of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Tilia euchlora, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. Tilia heterophylla, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Tilia platyphylios, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [1]. See [1] Gottshall et al., 1949; [2] Osbom, 1943. Tiliacora racemosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tillandsia usneoides, a higher plant (Southern Spanish moss), the active principle of which is an olive-green or yellow liquid extracted from the light-brown portions of the plant with acetone or chloroform. The extract is filtered, the filtrate evaporated, and the residue dissolved in ethanol. The antibiotic appears as the supernatant on centrifugjng. The unit is the least amount of an ethanol solution required to inhibit Staphylococcus aureus in 1 cc of broth for 48 hr. SPECTRUM.—Cryptococcus mococci, and Streptococcus

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

hominis, pneuhemolyticus are

[297] about as sensitive as Staphylococcus aureus. Candida albicans and Hemophilus influenzae are somewhat less sensitive. Escherichia coli, another strain of H. influenzae, Proteus vulaeruginosa are not garis, and Pseudomonas inhibited by dilutions of 1:50 [1], Aqueous extracts of Tillandsia usneoides are also reported to show little or no inhibition of growth in other tests in vitro against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas lumejaciens [2], See 11] Weld and Gunther, 1945; [2] Hayes, 1947. Tillandsia xephostachys, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tilletia tritici, as test organism in vitro, see CORN BACTERIA.

Tinea, as test organism in vitro, see JUGLONE. tinea capitis, clinical, see PODOPHYLLIN. Tiniaria scandens, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Titanotrichuni oldhamli, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tithonla rotundifolia, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Tithonia speciosa, a higher plant, aqueous extracts of the seed, flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Tithymaiopsis corollata, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. tobacco-mosaic virus, experimental infections, see YEASTS. For literature see Price, Gupta, and Wolcyrz, 1949. tobacco ring-spot virus, experimental infections, see Price, Gupta, and Wolcyrz, 1949. Toddalta aculeata, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Tolmiea menziesii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tolpls barbata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. tomatin, o r tomatine, see LYCOPERSICUM PIMPI-

NELLIFOLIUM. For literature see Fontaine et al., 1950; Wilson et al., 1950. tomato, a garden vegetable of the genus Lycopersicum, extracts of various strains of which are effective in vitro against Staphylococcus aureus, Salmonella paratyphi, Fusarium oxysporum f. melonis, F. oxysporum f. conglutinans, and F. oxysporum f. lycopersici, and ineffective against Salm. typhi, Phytomonas medicaginis v. phaseolicola, Ph. campestris. Ph. solanacearum, Bacillus stewartii, Actinomyces scabies, Erwinia carotovora, E. amylovora, and F. oxysporum f. niveum. See Little and G r u b a u g h , 1946. See also LYCOPERSICUM ESCULENTUM; LYCOPERSICUM PIMPINELLIFOLIUM; LYCOPERSICUM RACEMIGERUM.

TOXOFLAVIN

tonsillitis, clinical, see AUREOMYCIN; PENICILLIN.

Torenia fournieri, a higher plant, aqueous extracts of the flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Torilis anthrlscus, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Tonila spp., as test organisms in vitro, see ANTIBIOTIC X G

a n d BACILLUS s p .

Tonila cremoris, as test organism in vitro, see MYCOSUBTILIN.

Tonila histolytica, as test organism in vitro, see BACILLOMYCIN.

Tonila sphaerica, as test organism in vitro, see PSEUDOMONAS

FLUORESCENS.

Tonila suganti, a fungus which in vitro inhibits the growth of Aspergillus aureus, A. awamori, A. giganteus, A. gymnosardae, A. niger, A. ochraceus, A. oniki, A. oryzae, A. soya, Monascus purpureus, and Rhizopus nigricans and is ineffective against Debaromyces ayrocola, Saccharomyces cerevisiae, S. sake, and Torula suganii. See Okunuki, 1931. Torula utilis, as test organism in vitro, see ACTIDIONE.

Torulaspora

fermentati, as test organism

vitro, see ACTIDIONE.

in

Torulopsls sp., a fungus which is effective in vitro against blue-staining fungi. See Melin, 1933, 1934. Torulopsls dattila, as test organism in vitro, see ASPERGILLUS FACTOR; L U P U L O N AND H U M U L O N ; RHIZOCTONIA FACTOR.

Torulopsis delbruckli, as test organism in vitro, see

MYCOSUBTILIN.

Torulospora utilis, a yeast-like organism which is effective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. This action may be due to the production of acid. See Carpenter, 1945. Torulospora utilis v. major, a yeast-like organism which is effective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. This action may be due to the production of acid. See Carpenter, 1945. Torulospora utilis v. thermopbila, a yeast-like organism which is effective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. This action may be due to the production of acid. See Carpenter, 1945. Tovara virgin lana, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli [1]. Other extracts are reported to be effective in vitro against both Staph, aureus and E. coli [2]. See [1] Carlson, Douglas, and Robertson, 1948; [2] Carlson and Douglas, 1948a. Toxicodendron capense, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Toxodhim mucronatum, a higher plant, aqueous extracts of the commercial wood obtained from which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Bacillus anthracis. See Sanchez et al., 1948. toxoflavin, an antibiotic pigment produced by Bacillus cocovenans. It is isolated by saturating the culture with salt and extracting with

C r o s s references a r e indicated b y SMALL CAPITALS

TOXOPLASMOSIS, EXPERIMENTAL

[ 298 ]

chloroform. The formula is C«HsN4!. See Waksman, 1945. toxopfaunMxfo, experimental, see AUREOMYCIN; PENICILLIN;

STREPTOMYCIN.

tine I* Ufa, Hhitral, see PENICILLIN. T n r t r l o i | i n unim diraricatam, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Traclielospcnniim jasminoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. Sec Osborn, 1943. trachoma, «•IFAIL-AI, see AUREOMYCIN; PENICILLIN. Trechystemon Orientale, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Tradescantia blossfeldiana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tradescantia dinretica, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. Tradescantia vlrginiana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tragopogon pratensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phylomonas tumefaciens [2], See [1] Osbom, 1943; [2] Hayes, 1947. Trametes aiaskani, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. This antibiotic action may be due to the production of acid [1], The fungus is also reported to be ineffective against Staph, aureus and E. coli [2]. See [1] Robbins et al„ 1945; [2] Wilkins, 1947b. Trametes americana, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1,2]. See [1] Robbins et al., 1945; [2] Hervey, 1947. Trametes carbonaria, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Trametes carnea, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli [1]. The culture media of this fungus are weakly inhibitory for Staph, aureus and/or E. coli. [2]. See [1] Robbins et al., 1945; [2] Wilkins, 1947a. Trametes cervina, a fungus, the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus and/or Escherichia coli. See Wilkins, 1947a. Trametes cinnabarina, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Trametes cnbensis, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Trametes feel, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coll. This antibacterial activity may be due to the production of acid [1]. This

fungus is also reported to inhibit Staph, aureus and/or E. coli [2]. See [1] Hervey, 1947; [2] Wilkins, 1946b. Trametes gibbosa, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1,2]. Extracts of the sporophores of this fungus are also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [3]. See [1] Wilkins, 1946b; [2] Hervey, 1947; [3] Wilkins and Harris, 1944d. Trametes heteromorpha, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. This antibacterial activity may be due to the production of acid [1, 2], The culture media inhibit Staph, aureus at 1:64 [1], The fungus is also reported to be ineffective against Staph, aureus and E. coli [3]. See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1947b. Trametes hispida, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2], See [1] Robbins et al., 1945; [2] Hervey, 1947. Trametes lncana, a fungus which is weakly inhibitory in vitro for Staphylococcus aureus and/or Escherichia coli. See Wilkins, 1948. Trametes incerta, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1947a. Trametes isabeilina, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1] and b) to be ineffective against these two microorganisms [2], See [1J Hervey, 1947; [2] Wilkins, 1946b. Trametes lilaclno-gilva, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. This antibacterial activity may be due to the production of acid [lj. TTie culture media of this fungus are strongly inhibitory for Staph, aureus and/or E. coli [2]. Extracts of the sporophores are ineffective against these two microorganisms [3]. See [1] Hervey, 1947; [2] Wilkins, 1947a; [3] Mathieson, 1946. Trametes malicola, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. This antibiotic action may be due to the production of acid [1], The fungus is also reported to inhibit Staph, aureus and/or E. coli [2], See [1] Robbins et al., 1945; [2] Wilkins, 1947b. Trametes mollis, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be ineffective against these two microorganisms [2], Extracts of the sporophores of this fungus are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [3]. See [1] Hervey, 1947; [2] Wilkins, 1947a; [3] Wilkins and Harris, 1944d. Trametes morgan!!, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Trametes ochroleoca, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Trametes odorata, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Wilkins, 1948. Trametes pini, a fungus which is ineffective in

C r o s s references are indicated by SMALL CAPITALS

1299] vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1946b. Trametes protracta, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Wilkins, 1948. Trametes rtgkia, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Trametes robiniophila, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Trametes rubescens, a fungus which is reported a) to be effective in vitro against Staphylococcus aureus but not against Escherichia coli [1] and b) to be ineffective against these two microorganisms [2], The liquid culture medium of this fungus inhibits Staph, aureus in dilutions no greater than 1:64 [1], Extracts of the sporophores are ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [3]. See [1] Robbins et al., 1945; [2] Wilkins, 1946b; [3] Wilkins and Harris, 1944d. Trametes septum, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. This antibiotic action may be due to the production of acid [1], The fungus is also reported to inhibit Staph, aureus and/or E. coli [2], See [1] Robbins et al., 1945; [2] Wilkins, 1947b. Trametes serialis, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. This antibacterial activity may be due to the production of acid [1, 2], The culture media of this fungus are strongly inhibitory for Staph, aureus and/or E. coli [31. See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1947a. Trametes serpens, a fungus which is effective in vitro against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Mycobacterium phlei. See Hervey, 1947. Trametes suaveolens, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1, 2, 3], See [1] Hervey, 1947; [2] Robbins et al., 1945; [3] Wilkins, 1948. Trametes subrosea, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Trametes tenuis, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Hervey, 1947. Trametes variiformis, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. This antibacterial activity may be due to the production of acid. See Hervey, 1947. Tremella foliacea, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tremella fucifonnis, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Tremella mesenterica, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Pseudomonas aeruginosa [1]. See [11 Wilkins and Harris, 1944d; [2] Mathieson, 1946. Tremellodon gelatinosum, a fungus, extracts of the sporophores of which are reported a) to be effective in vitro against Staphylococcus

TRICHODERMA

LIGNORUM

aureus but not against Escherichia coli and Pseudomonas aeruginosa [1] and b) to be ineffective against Staph, aureus and E. coli [2], See [1] Wilkins and Harris, 1944d; [21 Mathieson, 1946. Treponema pallidum, as test organism in vitro, s e e BACITRACIN; GLIOTOXIN;

PENICILLIN.

Tricalysia kraussiana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Trichilla sp., a higher plant, extracts of the roots of which are slightly effective in the treatment of experimental malaria. See Spencer et al., 1947. Trichilla dregel, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Trichilla undulatifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Trichocladus grandifloras, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Trichoderma sp., a fungus, the culture media of which are effective in vitro against Staphylococcus aureus, Bacillus megatherium, and Bacterium jascians but not against Escherichia coli and Pseudomonas aeruginosa. See Cook and Lacey, 1945b. Trichoderma spp., as test organisms in vitro, see A C T I N O M Y C I N ; ANTIBIOTIC X G ; BACILLUS s p . ; FRADICIN; GLIOTOXIN; M Y C O S U B T I L I N . For litera-

ture see Arnstein et al., 1946a (Fusaria). Trichoderma album, a fungus which elaborates a lethal principle effective against Rhizoctonia solani and Rh. bataticola. See Weindling, 1934. Trichoderma koeningi, a fungus which is effective in vitro against Salmonella typhi and Endomycopsis albicans but not against Staphylococcus aureus. The culture media of this fungus inhibit Botrytis ailii but not Staph, aureus [1]. In another series of tests this fungus is reported to elaborate a lethal principle effective against Rhizoctonia solani and Rh. bataticola [2]. See [1] Brian and Hemming, 1947; [2] Weindling, 1934. As test organism in vitro, see L U P U L O N AND H U M U L O N . Trichoderma lignorum, a fungus which is ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa [1], In other tests in vitro this fungus is reported effective against Fusarium culmorum [2], Helminthosporium sativum [2], Rhizoctonia solani [3, 4, 6, 7], Rh. bataticola [4, 6], Phytophthora parasitica [3], P. citrophthora [4], Pythium spp. [3], P. debaryanum [7], Rhizopus spp. [3], Sclerotium rolfsii [3], Armillaria mellea [4], and Phymatotrichum omnivorum [5]. The lethal substance effective in vitro against the organisms in tests reported by Weindling [4] is unstable at high pH, decreasing in activity with decreasing hydrogen-ion concentration. Oxygenation hastens deterioration. Boiling for 1 or more hr does not completely destroy the activity. The hyphae and the filtrate of T. lignorum are also effective against Rh. solani and Rh. bataticola [6],

Cross references are indicated by

SMALL CAPITALS

TRICHODERMA VIRIDE

[3001

The toxic principle effective in vitro against organisms in tests reported by Allen and Haenseler [7] is inactivated by heating for 10 min at 100°C. Oxygenation for 5 min and exposure to air for 20 days inactivate the antibiotic [7], See [1] Wilkins and Harris, 1942; [2] Bisby et al„ 1933; [3] Weindling, 1932; [4] Weindling, 1934; [5] Brown, 1933; [6] Vasudeva and Sikka, 1941; [7] Allen and Haenseler, 1935. Trichoderma viride, a fungus which is effective in vitro against Staphylococcus aureus, Salmoalbicans. T h e nella typhi, and Endomycopsis culture media of this f u n g u s inhibit Staph, aureus and Botrytis allii See also GLIOTOXIN; VIRIDIN. See Brian and Hemming, 1947. As test organism in vitro, see TRICHOTHECIN. Tricholoma sp., a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. Tricholoma acerbum, a fungus, extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coil, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma albobrunneum, a f u n g u s , extracts of the s p o r o p h o r e s of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma album, a fungus, extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma ambustum, a f u n g u s which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Hervey, 1947. Tricholoma argyraceum, a fungus, extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma atrosquamosum, a f u n g u s , extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma aurantium, a f u n g u s , extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma bnfoniom, a fungus, extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, a n d Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma carnenm, a fungus, extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, a n d Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma cinerascens, a fungus, extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, a n d Pseudomonas aeruginosa. See Wilkins and H a r r i s , 1944d. Tricholoma coarctata, a fungus, extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946.

Tricholoma cognatnm, a fungus, extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma columbetta, a fungus, extracts of t h e s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma cuneifollum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Pseudomonas aeruginosa [1]. See [1] Wilkins and Harris, 1944d; [2) Mathieson, 1946. Tricholoma equestre, a fungus, extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma fulvum, a fungus, extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma gam bosom, a fungus, extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma grammopodioro, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma imbricatum, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma irinum, a fungus, extracts of the s p o r o p h o r e s of which are effective in vitro against Staphylococcus aureus and Escherichia aeruginosa. coli but not against Pseudomonas See Wilkins and Harris, 1944d. Tricholoma lascivum, a fungus, extracts of the s p o r o p h o r e s of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma leucocephalum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Sec Wilkins and Harris, I944d. Tricholoma melaleucum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma murinaceum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma nudum, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the sporop h o r e s of this fungus are reported a ) to inhibit Staph, aureus and E. coli but not Pseudomonas aeruginosa [2] and b ) t o be ineffective against Staph, aureus and E. coli [3]. T h e culture liquid and mycelial disks inhibit

Cross references are indicated by SMALL CAPITALS

[ 301 ] Staph, aureus and E. coli [2], See [1] Wilkins, 1947c; [2] Wilkins and Harris, 1944d; [3] Ma thieson, 1946. See also N U D I C ACIDS A AN D

B.

Tricholoma panaeolum, a fungus, the culture media of which are effective in vitro against Sta phylococcus aureus but not against Escherichia coli [1]. Extracts of the sporophores of this fungus inhibit Staph, aureus (2, 3] and E. coli [2, 3] but not Pseudomonas aeruginosa [J].. See [1] Wilkins, 1947c; [2] Mathieson, 1946; [3] Wilkins and Harris, 1944d. Tricholoma persoDatum, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. T h e culture liquid and mycelial disks of this fun gus inhibit Staph, aureus but not E. coli. See Wilkins and Harris, 1944d. Tricholoma polioleucum, a fungus, extracts of the sporophores of which are ineffective in vitro aga inst Staphylococcus aureus, Escherichia coll, and Pseudomonas aeruginosa. See Wilkins and Ha-rris, 1944d. Tricholoma portentosum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Sec Wilkins and Harris, 1944d. Tricholoma psammopum, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma putidum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma rutilans, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma saponaceum, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma sejunctum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Iricholoma sordldum, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma sulphureum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma terreum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus [1, 21, Escherichia coli [1, 2), and Pseudomonas aeruginosa [I]. See [1] Wilkins and Harris, 1944d; [2] Mathieson, 1946. Tricholoma tmncatum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli,

TRICHOPHYTON GRANULOSUM

and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma ustale, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Tricholoma virgatum, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Trichomonas foetus, as test organism in vitro, see

ACTIDIONE;

CHLORAMPHENICOL.

Trichomonas gallinae, as test organism in vitro, see

ACTIDIONE.

Trichomonas vaginalis. 1 As test organism in vitro, see A C T I D I O N E ; B O R R E L I D I N . 2 Treatment of clinical infections caused by, see A U R E O M Y CIN;

TYROTHRIC1N.

Trichophyton sp., as test organism in vitro, see JLGLONE.

Trichophyton spp., as test organisms in vitro, see LEPTOTAENIA

DISSECTA;

MYCOSUBTILIN;

RHUS

HIRTA.

Trichophyton acuminatum, as test organism in vitro, see C H L O R A M P H E N I C O L . Trichophyton album, as test organism in vitro, see A S P E R G I L L I C ACID; C H E I R O L I N E ; CLAVACIN; FUMIGACIN; GLIOTOX1N; MYCOPHENOL1C ACID; PENICILLIN; PROACTINOMYCIN.

Trichophyton asteroides, as test organism in vitro, see A S P E R G I L L I C A C I D ; C H E I R O L I N E ; C L A V A CIN; FUMIGACIN; GLIOTOXIN; MYCOPHENOLIC ACID; P E N I C I L L I C ACID; P E N I C I L L I N ; P R O A C T I N O MYCIN.

Trichophyton balcaneum, as test organism in vitro, see A S P E R G I L L I C A C I D ; C H E I R O L I N E ; C L A V A CIN;

MYCOPHENOLIC

ACID;

PROACTINOMYCIN.

Trichophyton cerebrifonne, as test organism in vitro, see A S P E R G I L L I C A C I D ; C H E I R O L I N E ; C L A V A CIN; FUMIGACIN; GLIOTOXIN; MYCOPHENOLIC ACID; P E N I C I L L I C ACID; P E N I C I L L I N ; P R O A C T I N O MYCIN.

Trichophyton crateriforme, a fungus which causes little or no inhibition in vitro of Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. As test organism in vitro, see

ANTIBIOTIC

X G .

Trichophyton decalvans, as test organism in vitro, see A S P E R G I L L I C A C I D ; C H E I R O L I N E ; C L A V A CIN;

M Y C O P H E N O L I C ACID;

PROACTINOMYCIN.

Trichophyton depressum, as test organism in vitro, see A S P E R G I L L I C A C I D ; C H E I R O L I N E ; C L A V A CIN;

M Y C O P H E N O L I C ACID;

PROACTINOMYCIN.

Trichophyton discoides, as test organism in vitro, see A S P E R G I L L I C A C I D ; C H E I R O L I N E ; C L A V A CIN;

M Y C O P H E N O L I C ACID;

PROACTINOMYCIN.

Trichophyton effractum, as test organism in vitro, see A S P E R G I L L I C A C I D ; C H E I R O L I N E ; M Y C O PHENOLIC

ACID;

PROACTINOMYCIN.

Trichophyton equinum, as test organism in vitro, see A S P E R G I L L I C ACID; C H E I R O L I N E ; C L A V A CIN; FUMIGACIN; GLIOTOXIN; MYCOPHENOLIC ACID; P E N I C I L L I C ACID; P E N I C I L L I N ; P R O A C T I N O M Y C I N ; TARDIN.

Trichophyton ferrugineum, as test organism in vitro, see P H T H I O C O L ; P L U M B A G O L . Trichophyton fumatum, as test organism in vitro, see A S P E R G I L L I C A C I D ; C H E I R O L I N E ; C L A V A CIN;

M Y C O P H E N O L I C ACID;

PROACTINOMYCIN.

Trichophyton granulosum, as test organism in vitro, see A S P E R G I L L I C A C I D ; C H E I R O L I N E ; C L A V A -

Cross references are indicated by

SMALL

CAPITALS

TRICHOPHYTON GYPSEUM C I N ; FUMIGACIN; ACID; PENICILLIN.

OLIOTOXIN;

[302] MYCOPHENOLIC

Trichophyton gypsenm, a fungus which gives doubtful results when tested in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 194S. As test organism in vitro, s e e ANTIBIOTIC X G ; CLAVACIN; LUPULON AND H U M U L O N ; PODOPHYLLIN; SUBTILIN; T H U J A PLICATA.

Trichophyton Interdigitale, a fungus which causes little or no inhibition in vitro of Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. As test organism in vitro, see ANTISMEGMATIS FACTOR; P E N A T I N ; SULFACTIN.

CHLORAMPHENICOL;

Trichophyton lactlcolor, as test organism

in

vitro, s e e ASPERGILLIC ACID; CHEIROLINE; CLAVAC I N ; MYCOPHENOLIC ACID; PROACTINOMYCIN; TAKDIN.

Trichophyton loaisiankmn, as test organism in vitro, s e e ASPERGILLIC ACID; CHEIROLINE; CLAVAC I N ; MYCOPHENOLIC ACID; PROACTINOMYCIN.

Trichophyton mentagrophytes, a fungus which causes little or no inhibition in vitro of Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. As test organism in vitro, s e e ACTIDIONE; ACTINOMYCIN; ANTIBIOTIC 3 5 1 0 ; ANTIBIOTIC " V " ; ASPERGILLUS FLAVUS; BACILL O M Y C I N ; BIFORMIN; CHAETOMIN; CHLORAMPHENICOL; EUMYCIN; FRADICIN; FUMIGACIN; LYCOPERSICUM PIMPINELLIFOLRJM; 2-METH-

o x Y - 1 , 4-NAPHTHOQUINONE; 5-METHOXY-P-TOLUQUINONE; MUSA SAPIENTUM; MYCOSUBTILIN; N E O M Y C I N ; PROTOANEMONIN; SOLANINE; STREPT O M Y C I N ; STREPTOTHRICIN; STUEPTOTHRICIN V I .

Trichophyton mentagrophytes v. and v. spp. Trichophyton gypseum and Trichophyton interdigitale (ultraviolet mutants), fungi which elaborate a factor antagonistic in vitro to Staphylococcus aureus, Streptococcus hemolyticus, Diplococcus pneumoniae, Neisseria catarrhalis, and Clostridium perfringens. It is reported inactive against penicillin-resistant Staph, aureus, Strep, fecalis, Bacillus subtilis, Aerobacter aerogenes, Serratia marcescens, Alcaligenes fecalis, Salmonella enteritidis, and Escherichia coli. See Peck and Hewitt, 1945. Trichophyton perskolor, as test organism in vitro, s e e ASPERGILLIC ACID; CHEIROLINE; CLAVAC I N ; MYCOPHENOLIC ACID; PROACTINOMYCIN.

Trichophyton plicatilis, as test organism in vitro, s e e ASPERGILLIC ACID; CHEIROLINE; CLAVACIN; MYCOPHENOLIC ACID; PROACTINOMYCIN.

Trichophyton purpureum, a fungus which is effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Robbins et al., 1945. As test organism in vitro, see ANTIBIOTIC X G ; PODOPHYLLIN; P R O T O A N E M O N I N ; T H U J A PLICATA.

Trichophyton rosacenm, a fungus which causes little or no inhibition in vitro of Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. As test organism in vitro, see MYCOPHENOLIC ACID.

Trichophyton rubrum, a fungus which is inactive in vitro against Staphylococcus aureus, Streptococcus hemolyticus, Diplococcus pneumoniae, Neisseria catarrhalis, and Clostridium perfringens. See Peck and Hewitt, 1945. As test o r g a n i s m in vitro,

see ACTIDIONE; ANTIBI-

OTIC 1 3 6 ; ANTIBIOTIC X G ; ASPERGILLUS FLAVUS; BACILLOMYCIN; MYCOPHENOLIC ACID; POLYPBPTIN.

Trichophyton sabouraodU, as test organism in vitro, s e e ASPERGILLIC ACID; CHEIROLINE; CHLORAMPHENICOL; CLAVACIN; FUMIGACIN; GLIOTOXIN; MYCOPHENOLIC ACID; PENICILLIN; PROACTINOMYCIN.

Trichophyton schoenleini, as test organism in vitro, s e e BACILLOMYCIN; STAPHYLOCOCCUS AUREUS.

CHLORAMPHENICOL;

Trichophyton snlphureum, as test organism in vitro, s e e ASPERGILLIC ACID; CHEIROLINE; CHLORAMPHENICOL; CLAVACIN; LEPTOTAENIA DISSECTA; MYCOPHENOLIC ACID; PROACTINOMYCIN; R H U S HIRTA.

Trichophyton tonsurans, a fungus which causes little or no inhibition in vitro of Staphylococcus aureus and Escherichia coli [1], In another series of tests in vitro this fungus is reported to elaborate a factor antagonistic to Staph, aureus, Streptococcus hemolyticus, Diplococcus pneumoniae, Neisseria catarrhalis, and Clostridium perfringens. It is reported inactive against penicillin-resistant Staph, aureus, Strep, fecalis, Bacillus subtilis, Aerobacter aerogenes, Serratia marcescens, Alcaligenes fecalis, Salmonella enteritidis, and E. coli [2], See [1] Robbins et al, 1945; [2] Peck and Hewitt, 1945. A s test o r g a n i s m in vitro, see ASPERGILLIC ACID;

ASPERGILLUS FLAVUS; CHEIROLINE; CHLORAMPHENICOL; CLAVACIN; FUMIGACIN; G H O T O X I N ; MYCOPHENOLIC ACID; PENICILLIC ACID; PENICILLIN; PROACTINOMYCIN; TARDIN.

Trichophyton violaceum, a fungus which causes little or no inhibition in vitro of Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro this fungus is reported to elaborate a factor antagonistic to Staph, aureus, Streptococcus hemolyticus, Diplococcus pneumoniae, Neisseria catarrhalis, and Clostridium perfringens. It is reported inactive against penicillin-resistant Staph, aureus, Strep, fecalis. Bacillus subtilis, Aerobacter aerogenes, Serratia marcescens, Alcaligenes fecalis, Salmonella enteritidis, and E. coli [2]. See [1] Robbins et al., 1945; [2] Peck and Hewitt, 1945. As test organism in vitro, see CHLORAMPHENICOL.

trichothecin, a colorless, crystalline, antifungal compound obtained from Trichothecium roseum [1], It is isolated by extraction with chloroform and purified by fractional precipitation and chromatographic separation on alumina. The substance is a neutral, unsaturated ketone having the empirical formula CisHisOi or Cir,H-ioOi. The crystals occur as long, fibrous needles. The m.p. is 118°C. Trichothecin is stable in acid solution and at pH 10; it undergoes hydrolysis at pH 12. Its activity is unaffected by the presence of cysteine. It is assayed by the degree of inhibition of the germination of Penicillium digitatum spores [2]. SPECTRUM.-—Staphylococcus aureus, Escherichia coli, and Bacillus subtilis are not affected by 0.4 mg cc. The following fungi are inhibited in vitro by the concentrations stated [3]. Inhibitory concentration Fungus in mg/cc Aspergillus fumigatus 0.08 Aspergillus niger 0.016 Cephalosporium longisporum 0.08 Chaetomium convolution 0.016 Cladosporium herbarum 0.016

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

[3031 Inhibitory concentration in mg ' cc 0.016 0.08 0.08 0.0032 0.08 0.08 0.08 0.00064 0.08 0.08 0.016

Fungus Fusarium graminearum Helminthosporium sacchari Mucor erecius Neurospora crassa Paecilomyces varioti Pénicillium caseicolum Pénicillium cilrinum Pénicillium digitatum Pénicillium expansum Pénicillium lilacinum Pénicillium meleagrinum Pénicillium nigricansjanczewskii sériés 0.08 Pénicillium notatum 0.08 Pénicillium oxalicum 0.016 Pénicillium roqueforti 0.08 Pénicillium spinulosum 0.016 Saccharomyces carlsbergensis 0.016 Stachybotris atra 0.08 Syncephalastrum racemosum 0.08 Thamnidium elegans 0.016 Trichoderma viride 0.08 Trichothecium roseum slight growth at 0.08 See [1] Freeman and Morrison, 1948; [2] Freem a n and Morrison, 1949a; [3] Freeman and Morrison, 1949b. Trichothecium sp., as test organism in vitro, see PEZIZA

SCLEROTIORUM.

Trichothecium roseum, a fungus which is ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [2], Pseudomonas aeruginosa [2], Salmonella typhi [1], and Endomycopsis albicans [1]. The culture media of this fungus inhibit Botrytis allii but not Staph, aureus [1], In another series of tests the culture filtrates of this fungus are reported to inhibit infections caused by Southern beanmosaic virus, tobacco-mosaic virus, and tobacco ring-spot virus [3], See [1] Brian and Hemming, 1947; [2] Wilkins and Harris, 1942; [3] Price, Gupta, and Wolcyrz, 1949. For further reference, see Johns, 1947, unpublished. See also ROSEIN; TRICHOTHECIN. As test organi s m in vitro, s e e ASPERGILLIC ACID; BERBERINE; CHEIROLINE; CLAVACIN; MYCOPHENOLIC ACID; PENICILLIC ACID; PEZIZA SCLEROTIORUM; PROACTINOMYCIN; SPIRAEA; TRICHOTHECIN; TYROTHRICIN; VIRIDIN.

Tricuspkiarla depeodeos, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Osborn, 1943. Trifolium arvense, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Trifolium hybridum, a higher plant, extracts of which are effective in vitro against Mycobacterium tuberculosis but not against Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition against Staph, aureus, E. coli, Envinia carotovora, and Phytomonas tumefaciens [2], See [1] Gottshall et al., 1949; [2] Hayes, 1947. Trifolium pannonicum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943.

TROCHOCARPA L A U R I N A

Trifolium pratense, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2], See [1] Osborn, 1943; [2] Hayes, 1947. Trifolium repeus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2]. See [1] Osborn, 1943; [21 Hayes, 1947. Trifolium uniflorum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Triglochin maritimum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Trillium grandiflonim, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Trillium sessile, a higher plant, aqueous extracts of which show little or no inhibition of growth whell tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Trilohin, an antitubercular substance extracted from the higher plant Cocculus trilobus. See Hasegawa, undated b. Triosteum perfoliatum, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli [1]. Extracts of the roots of this plant a r e slightly effective in the treatment of experimental malaria [2]. See [1] Carlson, Douglas, and Robertson, 1948; [2] Spencer et al., 1947. Triphasia trifolla, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tripterygium wilfordii, a higher plant, concentrated aqueous extracts of the Chinese drug prepared f r o m the vine of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Gaw and Wang, 1949. Tristania laurina, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Triteleia unifolium, a higher plant, aqueous extracts of the bulb, leaf, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Triticum vulgare, a higher plant, aqueous extracts of which are ineffective in vitro against Staphvlococcus aureus and Escherichia coli. See Osborn, 1943. Triumfetta sp., a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Trochocarpa laurina, a higher plant, aqueous extracts of which are ineffective in vitro against

Cross references are indicated by SMALL CAPITALS

TROCIA CRISPA

[304]

Staphylococcus aureus and Escherichia coli. See Osborn, 1943. T r o g b crispa, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Mathieson, 1946. Trollins enropaeos, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tropaeohim majos, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tropaeohim majus (Golden Gleam), a higher plant, aqueous extracts of the seed, seedling, and entire plant of which are effective in vitro against the spores of Neurospora crassa and are ineffective against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Tropaeohim mains (Golden Gleam Hybrid), a higher plant, aqueous extracts of the seedling but not of the seed and entire plant of which are effective in vitro against Staphylococcus aureus and Escherichia coli. Aqueous extracts of the entire plant inhibit the spores of Neurospora crassa. See Schnell and Thayer, 1949. Tropaeolum majus (Tall Giants), a higher plant, aqueous extracts of the flower, leaf, stem, and root of which are effective in vitro against the spores of Neurospora crassa. Only aqueous extracts of the flower inhibit Staphylococcus aureus, while none of these extracts inhibits Escherichia coli. See Schnell and Thayer, 1949. Tropaeolum majus v. nanum, a higher plant, aqueous extracts of the seed and seedling of which are effective in vitro against the spores of Neurospora crassa and are ineffective against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Tropaeolum perigrinum, a higher plant, aqueous extracts of the seedling of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Trophis racemosa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Trypanosoma spp., experimental infections, see BORRELIDIN; TRYPANOTOXIN.

Trypanosoma cruzi, as test organism in vitro, s e e GRAMICIDIN; TYROCIDINE.

Trypanosoma equlperdum. 1 As test organism in vitro, s e e A N E M O N I N ; CORYLOPHYLINE; DEM A T I U M s p . ; PARASORBIC ACID; PENICILLIL'M spp.; PENICILLIUM LUTEUM-PURPUROGENUM; PHYCOMYCES; PROACTINOMYCIN; STREPTOMYCIN.

2 Experimental infections, see PHYCOMYCES; PROACTINOMYCIN; STREPTOTHRICIN. 3 T r e a t m e n t

of clinical infections caused by, see BERBERINE. Trypanosoma gambiense. 1 As test organism in vitro,

s e e ASPERGILLUS NIGER; PROTOANEMONIN.

2 Experimental

infections, see ASPERGILLUS

NIGER.

Trypanosoma lewisll. 1 As test organism in vitro,

s e e ASPERGILLUS NIGER; GLIOTOXIN; GRAM-

ICIDIN; TYROCIDINE. 2 E x p e r i m e n t a l infections, s e e ASPERGILLUS

NIGER.

trypanotoxin, a substance isolated from Bacillus subtilis. The substance is destroyed at 73 C C. within 20 min. It is active in vitro against Spirillum and Leishmania but inactive against Borellia gallinarum. It fails to protect mice

inoculated with trypanosomes. Escherichia coli, B. prodigiosan, B. mesentericus, and B. pyocyaneus are ineffective when tested against trypanosomes. See Levaditi and Twort, 1911a and b. Tubaria autochthons, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wiikins and Harris, 1944d. Tubaria furfuracea, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wiikins and Harris, 1944d. Tubaria paludosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wiikins and Harris, 1944d. Tubaria pellucida, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wiikins and Harris, 1944d. t u b e r c u l o s i s . 1 Clinical, see AUREOMYCIN; CEPHERANTH1N; PENICILLIN; STREPTOMYCIN; TERRAMYCIN; VIOMYCIN. 2 E x p e r i m e n t a l , s e e AUREOMYCIN; BIFORMIN; BORRELIDIN; CEPHERANTHIN; CHLORAMPHENICOL; CLITOCYBINES; JAVANICIN; LICHENIFORMIN; LUPULON AND H U M U L O N ; NISIN; PYO COMPOUNDS; STREPTOMYCIN; SUBTILIN; TERRAMYCIN; TETRAHYMENA GELEII; USNIC ACID;

VIOMYCIN. For literature see Stansly and Ananenko, 1949. tuberculous sinus, clinical, see AUREOMYCIN. tularemia, clinical, see STREPTOMYCIN. Tulbaghla violacea, a higher plant, extracts of which are effective in vitro against Escherichia coli and Mycobacterium tuberculosis but not against Staphylococcus aureus. See Gottshall et al., 1949. Tulipa, a higher plant, aqueous extracts of the garden hybrid of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tulipa chrysantha, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tulipa clusiana, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tulipa cretica, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tulipa forsteriana, a higher plant, aqueous extracts of which are effective in vitro against Siaphvlococcus aureus and Escherichia coli. See Ösborn, 1943. Tulipa gesneriana, a higher plant, aqueous extracts of the flower, leaf, and bulb of which are effective in vitro against Escherichia coli but not against Staphylococcus aureus and the spores of Neurospora crassa. Aqueous extracts of the fruit inhibit Staph, aureus but not E. coli [1], Other aqueous extracts of this plant inhibit Staph, aureus and E. coli [2], See il] Schnell and Thayer, 1949; [2] Osbom, 1943. Tulipa greigi, a higher plant, aqueous extracts of which are effective in vitro against Staph-

Cross r e f e r e n c e s are indicated by SMALL CAPITALS

TYROC'iniNE

[305] ylococcus aureus and Escherichia coli. See Osborn, 1943. Tullpa grcigi v. kaufmanniana, a higher plant, aqueous extracts of the garden hybrid of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tuiipa kaufmanniana, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tuiipa koipakowskiana, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tuiipa linifolia, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tuiipa stellata, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tuiipa tarda, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tuiipa turkestanica, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tulostoma subfuscum, a fungus, extracts of the sporophores of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Mathieson, 1946. tumor ceils, mouse breast, inhibition in vitro, see

HEART.

turnip, a garden vegetable, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, Phytomonas campestris, and Ph. phaseoli. See Lucas and Lewis, 1944. Turraea obtusifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Turraea pubescens, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Tussacia pulchella, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Tussilago farfara, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], Concentrated aqueous extracts of the Chinese drug prepared from the flower of this plant are also ineffective in vitro against Staph, aureus and E. coli [2]. See [1] Osborn, 1943; [2] Gaw and Wang, 1949. Tylopilus felleus, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Typha angustifolia, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumejaciens. See Hayes, 1947. Typha latifolia, a higher plant, various extracts of which are effective in vitro against Staphylococcus aureus [1] but not against Escher-

ichia coli [1, 2], and Bacillus subtilis [2], See [1] Carlson, Douglas, and Robertson, 1948; [2] Sanders et al., 1945.

typhoid,

clinical,

see

AUREOMYCIN;

CHLORAM-

PHENICOL; PENICILLIN; POLYMYXINS; POLYPORIN; STREPTOMYCIN; TERRAMYCIN.

typhoid, fowl, experimental, see POLYMYXINS. typhoid carriers, see AUREOMYCIN. Typhula graminum, a fungus which in vitro inhibits the growth of Ophiobolus graminis. See Broadfoot, 1933a and b. typhus, 1 Clinical, see AUREOMYCIN; CHLORAMPHENICOL; TERRAMYCIN. 2 E x p e r i m e n t a l , s e e AUREOMYCIN; CHLORAMPHENICOL;

TERRAMYCIN.

tyrocidine, a crystalline polypeptide antibiotic, one of two active components of tyrothricin [1]. It is identical with the substance first designated as graminic acid. The crystalline preparation originally known as gramidinic acid is a mixture of free tyrocidine and its hydrochloride [2], Tyrocidine is separated from gramicidin, the other active component, by extracting the gramicidin from tyrothricin with a mixture of ether and acetone [2] or with warm absolute acetone alone [3], The residue is dissolved in boiling absolute alcohol, and crystallization of the hydrochloride is effected by the addition of alcohol containing hydrochloric acid. The product is recrystallized from absolute methanol. Tyrocidine hydrochloride crystals occur as fine colorless needles or rods with a m.jj. of 240°C. (corr., decomp.) [2], The substance contains tryptophane, tyrosine, and aspartic acid. It is resistant to the action of pepsin, trypsin, and papain [4], Human and rabbit erythrocytes are hemolyzed by tyrocidine [5|- The active material depresses the surface tension of aqueous solutions to a greater extent than does gramicidin. It is less affected than gramicidin by the action of serum [6], SPECTRUM.—In general tyrocidine is less active than gramicidin. It is effective in vitro against the following organisms: Bacillus anthracis [3] Clostridium spp. [3] Corynebacterium diphtheriae [7] Diphtheroid bacilli [7] Diplococcus pneumoniae [3] Escherichia coli [7] Gaffkya tetragena [3] Gonococci [8] Hemophilus spp. [7] Klebsiella spp. [7] Lactobacillus acidophilus [3] Leishmania tropica [9] Meningococci [8] Mycobacterium leprae [3] Mycobacterium phlei [3] Mycobacterium ranae [3] Mycobacterium tuberculosis [3] Neisseria spp. [7] Salmonella spp. [7] Shigella spp. [7] Staphylococcus aureus [3, 7] Staphylococcus citreus [3] Streptococcus spp. [7] Streptococcus fecalis [3] Streptococcus hemolvticus [3] Streptococcus mastitidis [3] Trypanosoma cruzi [9] Trypanosoma lewisi [9]

Cross references are indicated by SMALL CAPITALS

TYROTHRICIN

[306]

Bartonella bacilliformis and Leptospira icterohemorrhagiae are not affected by this agent [9]. TOXICITY.—The approximate lethal doses of tyrocidine for 20 gm mice are 0.5 mg i.v. and 1.8 m g i.p. [3]. Intraperitoneal inj of 2 m g is fatal f o r 25 gm mice within 48 hr [7], Fatal doses of tyrocidine result in respiritory death [3]. Oral administration of large doses is nontoxic [3]. The M T D for mice is also reported to be more than 1,000 mg/kg: p.o. or s.c., 20 m g / k g i.p., and 1.25 m g / k g i.v. [10). EXPERIMENTAL CLINICAL RESULTS. —Tyrocidine protects mice against pneumococci infections when given i.p. but is less effective in this respect than gramicidin. It is ineffective p.o., i.p., s.c., or i.v. against Kleb. pneumoniae and Salm. aertrycke infections in mice [7]. See also TYROTHRICIN. See [1] Hotchkiss and Dubos, 1940a; [2] Hotchkiss and Dubos, 1941; [3] Hoogerheide, 1944; [4] Hotchkiss, 1941; [5] Rammelkamp and Weinstein, 1941; [6] Heilman and Herrell, 1941; [7] Dubos and Hotchkiss, 1941; [8] Dubos, 1940; [9] Weinman, 1943; [10] Waksman, 1945. tyrothricin, a mixture of two antibiotic substances, gramicidin and tyrocidine, isolated f r o m the culture medium of a Bacillus sp. [1], later identified as B. brevis [2]. A protein-free preparation may be obtained by adjusting the whole culture to pH 4.5 to precipitate the cells and active material, extracting the active fraction f r o m the precipitate with acid acetone, and removing the acetone by distillation. The residue is taken up in water containing hydrochloric acid and the precipitate desiccatcd in vacuo, washed with ether, dissolved in 95% alcohol, and reprecipitated several times. The yield is a grayish-white powder insoluble in chloroform, sulphuric ether, petroleum ether, benzol, toluol, and water, and soluble in acetone, alcohol, dioxane, pyridine, and glacial acetic acid [3]. Tyrothricin does not dialyze through collodion membranes [1], It is not inactivated by pepsin [1], trypsin [1]. chymotrypsin [1], serum [4], or ascitic fluid [4], More recently it has been determined that the presence of 5cfo horse serum has a deleterious action on the potency of tyrothricin [5]. The activity is not affected by heating to 90 5 C. for 10 min at p H 2 or 9 [1]. An alcoholic solution of the protein-free material retains its activity f o r at least 3 mo at rm. temp. [3]. Tyrothricin is hemolytic for human and rabbit red blood cells; this action is due primarily to the tyrocidine content of the mixture [6]. SPECTRUM.—Tyrothricin is effective chiefly against gram-positive organisms [7], It is both bacteriostatic and bactericidal, and in some instances bacteriolytic as well [1]. The agent is effective in vitro against the following organisms: Diplococcus pneumoniae [1] Hemophilus ducreyi [8] Hemophilus influenzae [8] Saccharomyces cerevisiae [1] Staphylococcus aureus [1] Streptococcus hemolyticus [1] Streptococcus viridans [1] Tyrothricin is further reported to inhibit the growth in vitro of the following organisms in the concentrations shown [19]:

Organism Concentration Actinomyces scabies 1:80,000 Bacillus subtilis 1:1,280,000 Bacterium aroidae 1:10,000 Bacterium carotovorum 1:40,000 Bacterium tumefaciens 1:80,000 Corynebacterium michiganense 1:5,120,000 Corynebacterium sepedonicum 1:10,240,000 Gloeosporium musarum 1:5,000 Leuconostoc sp. 1:80,000 Phytophlhora erythroseptica 1:5,000 Pseudomonas syringae 1:5,000 Rhizoctonia crocorum 1:5,000 Rhizoctonia solani 1:20,000 Sclerotinia sclerotiorum 1:20,000 Stereum purpureum 1:5,000 Verticillium dahliae 1:5,000 Xanthomonas begoniae 1:40,000 Xanihomonas campestris 1:80,000 Xanthomonas malvacearum 1:160,000 The following are partially inhibited in vitro at concentrations of about 1:5,000: Alternaria citri, Botrytis cinerea, Byssochlamys fulva, Cladosporium herbarum, Claviceps purpurea, Fusarium avenaceum, F. culmorum, Myrothecium roridum, Penicillium digitatum, Pythium ultimum, Trichothecium roseum [19], Pityriasis versicolor is reported to be "not very sensitive" to tyrothricin [9], Tyrothricin is without effect in vitro on the following organisms: Bacillus polymyxa [19] Escherichia coli [1] Hemophilus parainiluenzae [8] Klebsiella pneumoniae [1] Penicillium expansum [19] Pseudomonas marginalis [19] Salmonella paratyphi [1] Salmonella typhi [1] TOXICITY IN ANIMALS.—In 20 gm mice the approximate lethal doses of tyrothricin are 1.6 mg i.p. and 0.1 mg i.v. Much larger doses are tolerated p.o. [10] It is also reported that the maximum tolerated dose in mice is more than 1,000 m g / k g p.o. and s.c., 10 m g / k g i.p., and 1.2 m g / k g i.v. [11], In chronic experiments the M T D for adult mice is 0.8 mg p.o. three times a day for 10 days [12], Adult rabbits survive single i.v. injs of 0.6 m g / k g [13]. In dogs, 10 daily i.v. injs of 0.2 m g / k g each have only slight toxic effect, but 0.4 m g / k g results in death of most of the animals before 10 injs have been given. Daily inj of 0.3 m g / k g is not fatal but it causes acute and chronic changes in the liver, spleen, kidney, heart, and lungs. [14] TOXICITY IN HUMAN BEINGS.—Subcutaneous and i.v. inj produces acute anemia, and topical administration is sometimes irritating to the skin [15]. A single inj of 200 mg into an infected pleural cavity was without adverse effect [10], EXPERIMENTAL CLINICAL RESULTS.— Single intra-abdominal injs of 2 mg suffice to protect a significant proportion of mice against pneumococci but are ineffective against Kleb. pneumoniae infections [4], Three daily doses p.o. of 0.4 mg each are very slightly effective against Strep, hemolyticus and type I pneumococcus infections in mice but are somewhat more beneficial in types II and III pneumococci infections [12]. Oral administration is

Cross references are indicated by SMAI.L CAPITALS

[307] without effect on the Lactobacillus acidophilus population in the feces of mice. This is thought to be due to the destruction of the activity by digestive juices [16], Tyrothricin has also been found ineffective against meningococcic infections in mice, but this failure may have been due to inactivation by the mucin in which the infecting organisms were administered [17]. In rabbits, 15 daily doses of 2 mg/kg [12] or 0.1 mg/kg [13] are completely ineffective against acute testicular syphilis.

URINE

pyema [10], osteomyelitis [10], pyoderma [15], ringworm, microsporic and trichophytic [9], sinusitis [10], suppurative wounds [10], sycosis barbae [15], and ulcers [10, 15]. Local administration of tyrothricin in Trichomonas vaginalis infections has marked beneficial effect. Relapses occur, however, and do not respond to further treatment with tyrothricin [18]. See [1] Dubos, 1939a; [2] Dubos and Hotchkiss, 1941; [3] Dubos and Cattaneo, 1939; [4] Dubos, 1939b; [5] Reedy and Wolfson, 1949; [6] Weinstein and Rammelkamp, 1941; [7] Dubos, 1939c; [8] Beeson, 1946; [9] Gate et al., 1948; [10] Hoogerheide, 1944; [11] Waksman, 1945; [12] Kolmer and Rule, 1946a; [13] Kolmer and Rule, 1946b; [14] MacLeod et al., 1940; [15] Long, 1948; [16] Weinstein and Rammelkamp, 1941; [17] Downs, 1943; [18] Weinman, 1943; [19] Gilliver, 1946.

VETERINARY CLINICAL RESULTS. — Instillation of tyrothricin into the udder of cows with mastitis due to Strep, agalactiae has been found to be very beneficial [10]. CLINICAL RESULTS.—The following conditions have responded satisfactorily to topical treatment with tyrothricin: abscesses [10], em-

u ulcerative colitis, clinical, see AUKEOMYCIN; BACITRACIN.

ulcers, clinical, see BACITRACIN; TYROTHRICIN.

Ulex europaeus, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Ulmus americana, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al„ 1945. Ulmus campestris, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1] and in vivo against experimental malaria [2], See [1] Osborn, 1943; [2] Spencer et al., 1947. Ulmus glabra, a tree, extracts of the litter of which are ineffective in vitro against Staphylococcus aureus. See Melin and Wiken, 1946. Ulmus procera, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. umbellatine, a yellow crystalline alkaloid obtained from the higher plants Berberis umbellata and B. insignis. It has been assigned the provisional formula C21H25O8N. It is slightly soluble in water. A 1:500 solution is lethal for paramecia. Leishmania tropica is inhibited by 1:50,000, and 1:100,000 is lethal in 12 days. Leishmania donovani and Endamoeba histolytica are not affected by 1:10,000. Local application of umbellatine dilates the conjunctival vessels of rabbits, cats, and guinea pigs. Subcutaneous administration also causes dilatation of local vessels in man and rabbits. In experimental animals it stimulates the smooth muscles of the viscera, depresses respiration, and constricts the bronchi. The agent is slightly anesthetic. Good results have been obtained in the local treatment, with umbellatine, of Oriental sore, which is caused by L. tropica. See Gupta and Kahali, 1944. Umbellularia californica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Umbilkaria delineata, a higher plant, aqueous extracts of which show little or no inhibition

of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Umbilicaria dillenii, a lichen, extracts of which are ineffective in vitro against Staphylococcus aureus and Bacillus subtilis. See Burkholder and Evans, 1945. Umbilicaria papulosa, a lichen, extracts of which are effective in vitro against Proteus vulgaris and Staphylococcus aureus a n d / o r Bacillus subtilis [1]. Extracts of this lichen are also reported to inhibit Staph, aureus and Pr. vulgaris but not B. subtilis, Escherichia coli, Aerobacter aerogenes, and Serratia marcescens [2]. See [1] Burkholder and Evans, 1945; [2] Burkholder et al., 1944. Uncaria guianensis, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Ungulina be tu Una, a fungus which is effective in vitro against Staphylococcus aureus and Escherichia coli. This antibacterial activity may be due to the production of acid. See Hervey, 1947. Unifolhim canadense, a higher plant, aqueous and ether extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Urena lobata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Urera baccifera, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. urethritis, nongonococclc, clinical, see AUREOM Y C I N ; CHLORAMPHENICOL;

TERHAMYCIN.

Urginea maritima, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. See Gottshall et al., 1949. urinary infections, clinical, see AUREOMYCIN; CHLORAMPHENICOL; P E N I C I L L I N ; S T R E P T O M Y C I N ; TERRAMYC1N.

urine. It has been reported that normal, fresh human urine contains antibacterial factors. See Dold and Deck, 1941 and 1942. See also INHIBIN.

Cross r e f e r e n c e s a r e indicated by SMALL CAPITALS

URS EVIA ANTHEOIDES

1308 J

Urdala antheoides, a higher plant, aqueous extracts of the seed and seedling of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Urtica dioica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Urtica arens, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli jl, 2], Mycobacterium tuberculosis [1], and Proteus X-19 [2], See [1] Gottshall et al., 1949; [2] Cardoso and Santos, 1948. Usnea spp., various unidentified lichens, extracts of some of which are effective in vitro against Staphylococcus aureus and/or Bacillus subtilis. See Burkholder and Evans, 1945. Usnea florida, a lichen, extracts of which are effective in vitro against Bacillus mycoides, B. subtilis, and Sarcina lutea, and ineffective against Aerobacter aerogenes, Alcaligenes fecalis, Diplococcus pneumoniae, Escherichia coli, Proteus vulgaris, Serratia marcescens. Staphylococcus albus. Staph, aureus, Streptococcus hemolyticus, and Strep, viridans. See Burkholder and Evans, 1945. ogiic acid, a crystalline antibacterial compound isolated from the lichens Cladonia sylvatica [1], C. cristatella [2], and Ramalina reticulata [lj. The fungal component of C. cristatella is responsible for the production of the active material [2]. It is obtained by boiling the lichens in acetone-alcohol solution, filtering, evaporating, dissolving the residue in boiling acetone, and recrystallizing. The m.p. is 191°192°C. The empirical formula is CUIHHOI; [3]. The structural formula is reported to be [4]: CHa I

c=o

HO

AAA:

HaC

o

H

VII

=

CHC

o v

CHs

O

CHs Usnic acid is readily soluble in hot acetone, ethanol, propylene glycol, and ether; moderately soluble in cold acetone; poorly soluble in hot petroleum ether, cold ethanol, and cold propylene glycol; and insoluble in water and hydrochloric acid. The crystals occur as yellow needles up to 1 in. long [3], SPECTRUM. — In dilutions of 50 micrograms/cc and less, usnic acid inhibits Mycobacterium tuberculosis avium, Myco, tuberculosis bovis, Myco, tuberculosis hominis, pneumococci, Staphylococcus aureus, and Streptococcus hemolyticus. The following are not inhibited by dilutions of 50 micrograms/cc: Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella aertrycke, Salm. typhimurium, Shigella spp., and Shig. sonnei [3]. TOXICITY.—In 25 gm mice s.c. injs of 2 mg are fatal, but doses of 1.5 mg are without

effect. Two or three s.c. injs of 1.25 mg given at intervals of 6, 22, or 24 hr are not lethal. In 250-350 gm guinea pigs, two s.c. injs of 30 mg, given 24 hr apart, are lethal, but three daily s.c. injs of 20 mg each are not [3]. It is also reported that the LDso for mice is 7 mg/10gm s.c. and 0.25 mg/10gm i.v. [4], EXPERIMENTAL CLINICAL RESULTS. —Usnic acid is without value in the treatment of pneumococcal infections in mice, but it retards the progress of tuberculosis in guinea pigs [1]. In 350-400 gm guinea pigs infected with tuberculosis, 10-20 mg daily for 3 wk has a beneficial effect [3], See [1] Marshak et al., 1947; [2] Castle and Kubsch, 1949; [3] Marshak, 1947; [4] Shibata et al., 1948. Ustilago avenae, as test organism in vitro, see CORN BACTERIA; NONE.

2-METHOXY-I,

4-NAPHTHOQUI-

Ustilago levis, as test organism in vitro, see CORN BACTERIA.

Ustilago zeae, as test organism in vitro, see CORN BACTERIA.

ustin, an antibiotic compound obtained from the culture filtrate and mycelia of the mold Aspergillus ustus [1], It is identical with an active substance extracted from A. ustus by Hogeboom and Craig [2] and probably identical with the material isolated by Kurung [3]. It is extracted from the filtered medium with various organic solvents or by charcoal adsorption [3], Ustin melts at 184°-186°C., has the probable formula CiuHuCbCis [1], is soluble in sodium carbonate solution [1, 3] and 95% ethanol [3], and is insoluble in water [3]. The activity is inhibited by serum albumin and other organic substances [1], Ustin is effective in vitro against Mycobacterium ranae and Myco, tuberculosis hominis at 1:200,000 to 1:400,000 and has only slight activity against staphylococci and streptococci [3]. Other organisms affected by this compound are the following [4]: Micrograms/cc required for Organism inhibition Bacillus mycoides 1.6 Bacillus subtilis 0.8 Escherichia coli more than 50 Klebsiella pneumoniae more than 50 Mycobacterium phlei 6 Mycobacterium smegma 13 Photobacterium fischeri 1.6 Staphylococcus aureus 6 Mice tolerate 6-8 mg [3]. Two other antibacterial substances, differing from ustin in chemical and physical properties but similar in biological activity, are produced by A. ustus [1, 21. See [1] Doering et al., 1946; [2] Hogeboom and Craig, 1946; [3] Kurung, 1945; [4] Kavanaugh, 1947b. L'stulina vulgaris, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], The culture medium of this fungus is also ineffective against Staph, aureus, E. coli, and Pseudomonas aeruginosa [2], See [1] Wilkins, 1947a; [2] Wilkins and Harris, 1943a. l'stulina zonata, a fungus, the culture media of which are weakly inhibitory in vitro for Staphylococcus aureus and/or Escherichia coli. See Wilkins, 1947a.

C r o s s r e f e r e n c e s a r e i n d i c a t e d b y SMALL CAPITALS

[309]

VERBASCUM BLATT ARIA

Uvaria rufa, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. uveitis, clinical, see AUREOMYCIN. U volar la grandiflora, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Uvularia perfoliata, a higher plant, aqueous extracts of which show little or no inhibition of

growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumejaciens. See Hayes, 1947. Uvularia sessisifolia, a higher plant, aqueous extracts of the fruit, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949.

vaccinia, experimental infections, see CHLORAM-

Valerianella radiata, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumejaciens. See Hayes, 1947. valicidin, an antibiotic produced by a strain of Streptomyces lavendulae. See Hutchison et al., 1949. Vallea stipnlaris, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vallesia glabra, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Vallisneria, a higher plant, aqueous extracts of the leaf and stem of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Vallisneria octandra, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vallisneria spiralis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vancouveria hexandra, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. Vangueria acutiloba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vangueria spinosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. varicella, clinical, see AUREOMYCIN. variola virus, experimental infections, see CHLOR-

PHENICOL.

Vaccininm angustifolium, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli but not against Mycobacterium tuberculosis. See Gottshall et al., 1949. Vaccinhni] caesariense, a higher plant, aqueous extracts of the leaf and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Vaccinium corymbosum, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Mycobacterium tuberculosis but not against Escherichia coli [1], Other extracts of this plant are reported to inhibit E. coli, Phytomonas campestris, and Ph. phaseoli but not Staph, aureus [2]. See [1] Gottshall et al., 1949; [2] Lucas and Lewis, 1944. Vacciuhui vacillans, a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. vaginitis, gonorrheal, clinical, see PENICILLIN. Vagpera racemosa, a higher plant, aqueous extracts of which are effective in vitro against the spores of Neurospora crassa, while ether extracts of the entire plant and aqueous and ether extracts of the berry, leaf, and stem are ineffective. None of these extracts inhibits Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Valeriana mexicana, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Valeriana officinalis, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Mycobacterium tuberculosis [1]. See [1] Gottshall et al., 1949; [2] Osborn, 1943. Valeriana pauciflora, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumejaciens. See Hayes, 1947. Valeriana phu, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Valeriana pyrenaica, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Valeriana sylvatka, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947.

AMPHENICOL.

Veltheimia verldifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Venidhim fatuosum, a higher plant, aqueous extracts of the seedling of which are effective in vitro against the spores of Neurospora crassa and are ineffective against Staphylococcus aureus and Escherichia coli. See Schnell and Thayer, 1949. Ventilago calyculata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Verbascum blattaria, a higher plant, extracts of the stems, seeds, and roots of which are effec-

C r o s s r e f e r e n c e s are indicated by SMALL CAPITALS

VERBASCUM NIGRUM

[310]

tive in vitro against Staphylococcus aureus and Escherichia coli. Extracts of the leaves inhibit Staph, aureus but not E. coli. See Carlson, Douglas, and Robertson, 1948. Verbascom nigrum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Verbascum spinosom, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Verbascum tbapsus, a higher plant, aqueous extracts of the leaf of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. Various other extracts of this plant are reported a) to be ineffective against Staph, aureus [2, 3], E. coli [2, 3], and Mycobacterium tuberculosis [3] and b) to inhibit Staph, aureus [4]. In another series of tests, the spring rosette, and the spring rosette and root of this plant in vitro are reported to inhibit Erwinia carotovora and Phytomonas tumefaciens but not to inhibit Staph, aureus and E. coli. The leaves (after flowering) are reported inactive against all four test organisms [5], See [1] Schnell and Thayer, 1949; [2] Osborn, 1943; [3] Gottshall et al-, 1949; [4] Lucas and Lewis, 1944; [5] Hayes, 1947. Verbena angustifoiia, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli [1 j. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2]. See [1] Carlson, Douglas, and Robertson, 1948; [2] Hayes, 1947. Verbena aubletia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Verbena canadensis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Verbena chamaedrifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Verbena corymbosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escheiichia coli. See Osborn, 1943. Verbena erinoides, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Verbena hastata, a higher plant, aqueous and ether extracts of the flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other extracts of this plant inhibit Staph, aureus and E. coli [2]. See [1] Schnell and Thayer, 1949; [2] Carlson, Douglas, and Robertson, 1948. Verbena hortensis, a higher plant, aqueous extracts of the seed and aqueous and ether extracts of the leaf and stem of which are effective in vitro against the spores of Neurospora crassa while aqueous and ether extracts of the root are ineffective. Only aqueous extracts of the leaf inhibit Escherichia coli and

only ether extracts of the leaf inhibit Staphylococcus aureus. See Schnell and Thayer, 1949. Verbena litoralis, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Verbena officinalis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Verbena urticifolia, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Verbena venosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Verbesina occidentalis, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Vernonia altissima, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Vernonia cinerea, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Vernonia fasciculata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vernonia noveboracensls, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Veronica agrestis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Veronica anagailis, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Veronica armena, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Veronica arvensis, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Veronica beccabunga, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Veronica chamaedrys, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Veronica diosmifolia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Veronica glauca, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Veronica iatifoiia, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Veronica officinalis, a higher plant, aqueous extracts of which are ineffective in vitro against

C r o s s r e f e r e n c e s a r e indicated by SMALL CAPITALS

[311] Staphylococcus aureus and Escherichia coli [1], Other extracts inhibit Staph, aureus but not E. coli and Mycobacterium tuberculosis [2]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition against Staph, aureus, E. coli, Envinia carotovora, and Phytomonas tumefaciens [3], See [1] Osborn, 1943; [2] Gottshall et a]., 1949; [3] Hayes, 1947. Veronica speciosa, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Veronica spicata, a higher plant, aqueous and ether extracts of the flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. Aqueous extracts of the seed are ineffective against Staph, aureus and E. coli. See Schnell and Thayer, 1949. Veronica traversil, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Verticillium sp., a fungus which is ineffective in vitro against Staphylococcus aureus, Salmonella typhi, and Endomycopsis albicans. The culture media of this fungus are ineffective against Staph, aureus and Botrytis allii. See Brian and Hemming, 1947. Verticillhiin alboatrum, a fungus which is ineffective in vitro against Staphylococcus aureus. Salmonella typhi, and Endomycopsis albicans. The culture media of this fungus are ineffective against Staph, aureus and Botrytis allii. See Brian and Hemming, 1947. As test organi s m in vitro,

s e e BACILLUS VULGATUS; MUSARIN.

For literature see Arnstein et al., 1946a (Fusaria). Vertlclllhim buxi, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Verticil]him dahiiae, as test organism in vitro, s e e ASPERGILLIC ACID; BERBERINE; CHEIROLINE; CLAVACIN; G H O T O X I N ; MYCOPHENOLIC ACID; PENICILLIC ACID; N O M Y C I N ; SPIRAEA; TYROTHRICIN. F o r

BURDOCK; MUSARIN; PROACTIliterature

see Arnstein et al., 1946a (Fusaria). Verticordia brownii, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi [1, 2]. See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Verticordia monodelpha, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi [1, 2], See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Verticordia plumosa, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus but not against Salmonella typhi fl, 2], See [1] Atkinson and Rainsford, 1946; [2] Atkinson, 1949. Vestla lyciodes, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Vibrio cholerae. 1 As test organism in vitro, see ALLICIN; AYFIVIN; CITRININ; FUSCIN; GEODIN; GRAMICIDIN S ; HERQUEIN; LICHENIFORMIN; M I CROCOCCI; NIDULINE; NOTALYSIN; NOTATIN; PENICILLIN; POLYMYXINS; POLYPORIN; PROTOANBMONIN; P S E U D O M O N A S FLUORESCENS; P S E U -

VIBURNUM

DOMONAS PUTIDA. 2 see

PRUNIFOI.IUM

Experimental

infections,

POLYPORIN.

Vibrio comma, as test organism in vitro, see ANTISMEGMATIS FACTOR; AYFIVIN; BACILLUS MESENTERICUS; CHLORAMPHENICOL; C O P T I S CHINENSIS; ESCHERICHIA COLI; K O J I C ACID; L E P T O TAENIA MULTIFEDA; LITMOCIDIN; L U P U L O N AND H U M U L O N ; N E O M Y C I N ; PENATIN; P S E U D O M O N A S FLUORESCENS; SUBTILIN; SULFACTIN.

Vibrio, El Tor, as test organism in vitro, see COLICINE;

HERQUEIN.

Vibrio metchnfltovll, as test organism in vitro, s e e K O J I C ACID.

Vibrio protens, as test organism in vitro, see K O J I C ACID.

Vibrio schaykflliensis, as test organism in vitro, s e e K O J I C ACID.

Viburnum acrifolhim, a higher plant, aqueous and ether extracts of the leaf of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Viburnum buddleifoUum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Viburnum burejacteum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osbom, 1943. Viburnum carlesii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Viburnum cotonifollum, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Viburnum davidii, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Viburnum fragnuu, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coll. See Osborn, 1943. Viburnum Ian tana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coll. See Osborn, 1943. Viburnum macrocephainm, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Viburnum opulus, a higher plant, aqueous extracts of the berry, leaf, and stem of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other aqueous extracts of this plant are also ineffective against Staph, aureus and E. coli [2]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [3]. See [1] Schnell and Thayer, 1949: [2] Osborn, 1943; [3] Hayes, 1947. Viburnum prunifoUnm, a higher plant, aqueous extracts of the leaf but not of the fruit of which are effective in vitro against Staphylococcus aureus. Neither of these extracts inhibits Escherichia coli. See Schnell and Thayer, 1949.

C r o s s r e f e r e n c e s a r e indicated b y SMALL CAPITALS

VIBURNUM SARGENTI

[312]

VHmrnam nrgcnti, a higher plant, aqueous extracts of the seed of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. V i n n u m tinu, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. VBrnrnom utile, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vkia cracca, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1]. In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2]. See [1] Osborn, 1943; [2] Hayes, 1947. Vkia faba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vicia sativa, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1,2], Escherichia coli [1,2], and Mycobacterium tuberculosis [2]. See [1] Osborn, 1943; [2] Gottshall et al„ 1949. Vkia unijuga, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. VUlamilla peruviana, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vinca herbacea, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vinca minor, a higher plant, various extracts of which are ineffective in vitro against Staphylococcus aureus [1], Escherichia coli [1,2], and Bacillus subtilis [2], In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [3]. See [1] Osborn, 1943; [2] Sanders et al., 1945; [3] Hayes, 1947. Vinca minor v. alba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vinca rosea, a higher plant, aqueous extracts of the seed, seedling, flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa [1]. Other aqueous extracts of this plant are also ineffective against Staph, aureus and E. coli [2], while extracts of the root are slightly effective in the treatment of experimental malaria [3]. See [1] Schnell and Thayer, 1949; [2] Osborn, 1943; [3] Spencer et al., 1947. Vinca rosea v. alba, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vincent's infection, clinical, see PENICILLIN. Vincetoxkum nigrum, a higher plant, aqueous extracts of which are ineffective in vitro against

Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vincetoiknm officianale, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Viola sp., a higher plant, extracts of which are ineffective in vitro against Bacillus subtilis and Escherichia coli. See Sanders et al., 1945. Viola cornota, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Viola cucnilata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Viola jooi, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Viola odorata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Viola papiiionacea, a higher plant, aqueous extracts of which show little or no inhibition of growth when tested in vitro against Staphylococcus aureus, Escherichia coli, Erwinia carotovora, and Phytomonas tumefaciens. See Hayes, 1947. Viola striata, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Viola tricolor, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Viola tricolor v. hortensis, a higher plant, aqueous extracts of the flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. violacein, a crystalline antibiotic isolated from the cells of Chromobacterium violaceum. The violet-black microcrystals in the form of thick needles and elongated rectangles are isolated by extraction with acetone followed by treatment with chloroform, ether, and pyridine [lj. Violacein is both bacteriostatic and bactericidal in vitro for Staphylococcus aureus. It has no antiphagocytic action against guinea-pig polymorphonuclear leucocytes. Mice weighing 8.5-16 gm tolerate single i.p. injs of 1-2 mg. While it gives no absolute in vivo protection against pneumococcic infections in mice, violacein does delay death in some cases [2], See [1] Strong, 1944; [2] Lichstein and Van de Sand, 1946. viomycin, a new antibiotic derived from a soil actinomycete. Its m.p. is 283°C. and [a]D32° (1% in water). Strongly basic groups are present; it forms a sulphate soluble in water, is stable at pH 5 at rm. temp., yields 2.7% Van Slyke nitrogen, and gives positive Saguchi and Fehling's tests. The antibiotic is active in vivo against tuberculosis and is apparently specific for mycobacteria. It has been reported as too toxic for long-term diseases like tuberculosis (Welch). It is more active in vivo and in vitro against

Cross references are indicated by SMALL CAPITALS

[3131 tuberculosis than is terramycin and is active against streptomycin-resistant strains. It is slightly better than streptomycin at 40,000 units per day in guinea pigs with tuberculosis (Steenken). At 4 mg/day in guinea pigs with tuberculosis, viomycin nearly tripled their life span as compared with controls. A neurotoxic effect was noted in cats given 100 mg/kg/day, and in dogs there was renal damage at 100 mg/kg/day. At 50 mg/kg/day, dogs seemed to tolerate the drug satisfactorily (Hobby). In human beings 2 to 2.5 gm/day in divided doses given twice daily has been administered to tuberculous patients who had relapsed after para-aminosalicylic acid or streptomycin and who were considered poor risks. At the time of the report, no effect had been observed in two patients after 52 and 58 days; in a third kept on the drug for 72 days the fever never dropped; in a fourth, fever returned after 121 days; and in a fifth, the drug was still being administered after 145 days. In this series there was no vestibular, auditory, or renal damage. The eosinophile count, however, was down 33%, and there was, in addition, some change in electrolyte balance (Muschenheim). See Minutes of the Ninth Streptomycin Conference, 1950. vtridin, a crystalline antifungal substance elaborated by Trichoderma viride. The active material is obtained by extracting the culture filtrate with chloroform, evaporating the extract in vacuo, and crystallizing from ethanol. The crystals are colorless, rodlike prisms which decompose without melting at 217°-223°C. and which are almost insoluble in ether and camphor. Aqueous solutions are unstable except at a low pH. Viridin does not contain nitrogen, sulphur, or halogens. SPECTRUM.—Viridin prevents germination of the conidia of Botrytis allii at 0.005 micrograms/cc. Fusarium spp., Trichothecium roseum, and Cephalosporium spp. have about the same order of sensitivity. Concentrations of 3-6 micrograms/cc are required to inhibit some spp. of Aspergillus and Penicillium. Viridin is not markedly bacteriostatic. See Brian and McGowan, 1945. Visearla ocolata, a higher plant, aqueous extracts of the root of which are effective in vitro against Escherichia coli, while aqueous extracts of the seedling, flower, leaf, and stem are ineffective. None of these extracts inhibits Staphylococcus aureus and the spores of Neurospora crassa. See Schnell and Thayer, 1949. Vtecum album, a higher plant, aqueous extracts

WHITFIELDIA LATERITA

of which are ineffective in vitro against Staphylococcus auieus and Escherichia coli. See Osborn, 1943. Vltex agnns-castas, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vltex volkensU, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vitis blcolor, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Vitis inconstans, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Vitts labrnsca, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli [1], In another series of tests in vitro aqueous extracts are reported to show little or no inhibition of growth against Staph, aureus, E. coli, Erwinia carotovora, and Phytomonas tumefaciens [2], See [1] Osborn, 1943; [2] Hayes, 1947. Vitis tiliaefolla, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Vitis vinifera, a higher plant, extracts of which are ineffective in vitro against Staphylococcus aureus [1, 2], Escherichia coli [1, 2], and Proteus X-19 [1]. See [1] Cardoso and Santos, 1948; [2] Osborn, 1943. Vitis vulplna, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli. See Carlson, Douglas, and Robertson, 1948. Volotella boxi, a fungus which is ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Robbins et al., 1945. Volntella frnctl, as test organism in vitro, see ACTINOMYCES ALBUS; BACILLUS SUBTILIS; SERRATIA MARCESCENS.

Volvarla bombycina, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d. Volvaria speclosa, a fungus, extracts of the sporophores of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. See Wilkins and Harris, 1944d.

W

Waldsteinia geoldes, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osborn, 1943. wallflower, see CHEIROLINE. Warburgia ngandensis, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Well's disease. 1 Clinical, see PENICILLIN. 2 Experimental, see AUREOMYCIN. Westringia rosmariniformis, a higher plant, aqueous extracts of which are ineffective in vitro

against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. wheat bran, an antibiotic compound having the characteristics of fatty acids has been extracted from wheat bran. The water-soluble potassium salt is active in vitro against Micrococcus conglomeratus, Staphylococcus aureus, and Streptococcus fecalis, and inactive against Escherichia coli. See Humfeld, 1947. wheat floor, see PUROTHIONIN. Whltfieldla laterfta, a higher plant, aqueous extracts of which are ineffective in vitro against

Cross references are indicated by

SMALL CAPITALS

WHOOPING COUGH

[314]

Staphylococcus aureus and Escherichia coli. See Osbom, 1943. »liiiiHihi cough, clinical, see C E P H E R A N T H I N ; PERTUSSIS. WHbramtta Mbbcoides, a higher plant, extracts of which are reported to be ineffective in vitro against Staphylococcus aureus, Escherichia coli, and Proteus X-19. See Cardoso and Santos, 1948. WWarta sinensis, a higher plant, aqueous extracts of which are ineffective in vitro against

Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Wojnowicia graminis, a fungus which in vitro inhibits the growth of Ophiobolus graminis. See Broadfoot, 1933a and b. wonnds, infected, clinical, see BACITRACIN; P E N I CILLIN;

TYROTHRICIN.

Wrightia coccinea, a higher plant, aqueous extracts of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Osbom, 1943.

X X n i t h h w texana, a higher plant, aqueous extracts of the flower, leaf, stem, and root of which are ineffective in vitro against Staphylococcus aureus, Escherichia coli, and the spores of Neurospora crassa. See Schnell and Thayer, 1949. XantMnm amerlcannm, a higher plant, extracts of which are effective in vitro against Staphylococcus aureus and Escherichia coli [1,2], See [1] Carlson, Douglas, and Robertson, 1948; [2] Carlson and Douglas, 1948a. Xanthfam commune, a higher plant, aqueous extracts of the green bur of which are effective in vitro against Staphylococcus aureus but not against Escherichia coli. See Schnell and Thayer, 1949. XantMnm pennsylvanicnm, a higher plant, various extracts of which are reported a) to be effective in vitro against Staphylococcus aureus and Escherichia coli [1, 2] and b) to inhibit Bacillus subtilis but not E. coli [3]. See [1] Carlson, Douglas, and Robertson, 1948; [2] Carlson and Douglas, 1948a; [3] Sanders et al., 1945. Xanthinm spinosom, a higher plant, extracts of which are ineffective against experimental malaria. See Spencer et al., 1947. Xanthoceras sorfoifolta, a higher plant, aqueous extracts of which are ineffective in vitro against Staphylococcus aureus and Escherichia coli. See Osborn, 1943. Xanthomonas begonlae, as test organism in vitro, s e e ASPERGILLIC ACID; BERBERINE; BURDOCK; CHEIROLINE; CLAVACIN; GLIOTOXIN; M Y COPHENOLIC ACID; P R O A C T I N O M Y C I N ; SPIRAEA; TYROTHRICIN.

Xanthomonas campestrls, as test organism in vitro, s e e ASPERGILLIC ACID; BURDOCK; CHEIROLINE; CLAVACIN; GLIOTOXIN; HELVOLIC ACID; M Y C O P H E N O L I C ACID; PENICILLIC ACID; PROACT I N O M Y C I N ; SPIRAEA," T Y R O T H R I C I N .

Xanthomonas malvaceanom, as test organism

in vitro, s e e BERBERINE; BURDOCK; CHEIROLINE; CLAVACIN; GLIOTOXIN; HELVOLIC ACID; MYCOP H E N O L I C ACID; P E N I C I L L I C ACID; PROACTINOM Y C I N ; SPIRAEA; TYROTHRICIN.

Xanthomonas tnuishicens f. sp. cereal is, infections in plants, see SUBTILIN. Xanthomonas translncens f. sp. hordel-avcnae, as test o r g a n i s m in vitro, TAS; M U S A

see IPOMOEA BATA-

SAPIENTUM.

xanthomycins A and B, two yellow antibiotic substances o b t a i n e d f r o m an unidentified Streptomyces designated as Streptomyces 94. Xanthomycin A has been obtained as the crystalline reineckate from which the hydrochloride derivative can be synthesized; xanthomycin B has not yet been prepared in crystalline form.

The reineckate of xanthomycin A occurs as long orange needles. The m.p. is 165°-170°C. (decomp.) and the empirical formula, C38H57 NiiOnS4Cr. It is insoluble in cold water and soluble in warm methanol and in acetone. Both xanthomycins are stable in acid solution and unstable at pH 6. There is no loss of activity in 3N hydrochloric acid at rm. temp, for 1 hr, a 90% loss when heated to 100°C. for 25 min at pH 6, and only 14