Update on Urinary Tract Infections [1 ed.] 9789390020997, 9789352701728

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Update on Urinary Tract Infections

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Update on Urinary Tract Infections

Editor

Rakesh Khera MBBS  MS  MCh (Urology)  DNB (Urology)  MNAMS

Director Uro-Oncology and Training Programme Department of Urology, Robotics and Renal Transplant Medanta—The Medicity Gurugram, Haryana, India

Foreword

Naresh Trehan

   The Health Sciences Publisher New Delhi | London | Panama

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Jaypee Brothers Medical Publishers (P) Ltd Headquarters Jaypee Brothers Medical Publishers (P) Ltd. 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 E-mail: [email protected] Overseas Offices J.P. Medical Ltd. 83, Victoria Street, London SW1H 0HW (UK) Phone: +44-20 3170 8910 Fax: +44(0)20 3008 6180 E-mail: [email protected] Jaypee Brothers Medical Publishers (P) Ltd. 17/1-B, Babar Road, Block-B, Shaymali Mohammadpur, Dhaka-1207 Bangladesh Mobile: +08801912003485 E-mail: [email protected]

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Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2018, Jaypee Brothers Medical Publishers The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book. All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher i s not a ssociated with a ny product o r vendor mentioned in this book. Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contra indications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book. This b o ok i s s o ld o n t h e u n derstanding t h at t h e p u blisher i s n o t e n gaged i n p r oviding p r ofessional m e dical services. If such advice or services are required, the services of a competent medical professional should be sought. Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity.

Inquiries for bulk sales may be solicited at: [email protected]

Update on Urinary Tract Infections First Edition: 2018 ISBN: 978-93-5270-172-8

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Dedicated to My teachers

Dr Ravinder Narang the man who taught me what surgery is and how to do it. The basics and the way forward was shown by him.

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Dr Rajesh Ahlawat the man who showed me what urology means and how to become good in it. He showed me the advances in urological surgical care.

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Contributors Olajide O Abiola Department of Surgery Bowen University Teaching Hospital Ogbomoso, Oyo State, Nigeria

Arif Akhtar  MBBS MS MCh (Urology) Senior Registrar PGIMER, Chandigarh Dr Ram Manohar Lohia Hospital New Delhi, India

Rajat Arora  MBBS MS MCh Associate Consultant Urology and Kidney Transplant Max Superspeciality Hospital New Delhi, India

Sohrab Arora  MS MCh Vattikuti Urology Institute Henry Ford Hospital Detroit, Michigan, USA

Sushil Bhatia  MCH (Urology) Senior Consultant Urologist and Kidney Transplant Surgeon Choithram Hospital and Research Center Indore, Madhya Pradesh, India

TBS Buxi  MD (Radiology) Chairperson CT/MRI Department Sir Gangaram Hospital New Delhi, India

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Prasun Ghosh  MS DNB (Genitourinary Surgery) MNAMS Associate Director Robotics and Urology Head of Renal Transplantation Division of Urology, Robotics and Renal Transplantation Kidney and Urology Institute Medanta—The Medicity Gurugram, Harayana, India

Jamaluddin 

MS (Surgery)

DNB Resident Medanta—The Medicity Gurugram, Haryana, India

Nikhil Khattar  MCH (Urology) Associate Director Reconstructive and Female Urology Medanta—The Medicity Gurugram, Haryana, India Formerly Professor of Urology PGIMER, Chandigarh Dr Ram Manohar Lohia Hospital New Delhi, India

Rakesh Khera MBBS MS MCh  (Urology)

DNB  (Urology) MNAMS

Director Uro-Oncology and Training Programme Department of Urology Robotics and Renal Transplant Medanta—The Medicity Gurugram, Haryana, India

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Update on Urinary Tract Infections

Vijay Kher  DM (Nephrology)

Varun Mittal  MBBS MS MCh

Chairman Division of Nephrology and Kidney Transplant Medicine Kidney and Urology Institute Fortis Escorts Hospital New Delhi, India

Urology and Kidney Transplant Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow, Uttar Pradesh, India Fellowship in Minimal Invasive and Robotic Urology Medanta—The Medicity Gurugram, Haryana, India Obs Fellowship in Advanced Robotic Surgery University of Miami, USA Consultant Urology Medanta—the Medicity Gurugram, Haryana, India

Anup Kumar  MS MCh (Urology-AIIMS) DNB (Urology) MNAMS

Professor and Head Department of Urology and Renal Transplant Expert Panel Member of Apex Technical Committee to Notto Member Secretary of Tumor Board Vardhman Mahavir Medical College and Safdarjang Hospital New Delhi, India

Niraj Kumar  MCH (Urology) Assistant Professor Urology and Renal Transplant Vardhman Mahavir Medical College and Safdarjang Hospital New Delhi, India

Pankaj N Maheshwari  MCH (Urology) Chief of Urology Fortis Hospital Mulund, Goregaon Mumbai, Maharashtra, India

Ashwin Mallya  MS MRCS (Ed) MCh Kidney and Urology Institute Fortis Escorts Hospital New Delhi, India

Chitra Mehta  DNB (Respiratory Medicine)

FNB (Critical Care)

Associate Director Critical Care Medanta—The Medicity Gurugram, Haryana, India

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Prashant Mulawkar  MBBS DGO MS

(Surgery) DNB (Surgery) MCh (Urology) DNB

Pratibha Narang  MD Director Professor Microbiology Ex-Dean Mahatma Gandhi Institute of Medical Sciences Wardha, Maharashtra, India

Udit Narang  MD PGDGM DHA Associate Professor Medicine Maharishi Markandeshwar Institute of Medical Sciences and Research Ambala, Haryana, India

Rishi Nayyar  MCH (Urology) Assistant Professor Department of Urology All India Institutes of Medical Sciences New Delhi, India

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Contributors

Anil Sharma  MCh (Urology)

Anurag Yadav  MD (Radiology)

Associate Consultant Medanta—The Medicity Gurugram, Haryana, India

Senior Consultant Department of Radiodiagnosis Sir Gangaram Hospital New Delhi, India

Swapnil Sheth  MD (Radiology) Associate Consultant Department of Radiodiagnosis Sir Gangaram Hospital New Delhi, India

Vinayak Wagaskar  MS MCh (Urology)

ix

Siddarth Yadav  MS MCh Senior Resident Department of Urology All India Institute of Medical Sciences New Delhi, India

Lecturer and Urologist College of Medicine Bowen University Teaching Hospital Ogbomoso, Oyo State, Nigeria

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Foreword Urinary tract infection is a very common but underestimated problem. In India there are more than 10 million reported cases of UTI per year. These figures reflect the enormity of it and most of us would get to see their fair share in the outpatients department. The varied spectrum that UTI presents itself is mind boggling cutting across age groups, sex, associated comorbidities, immune-suppression/compromised status, endemic areas and many more. The aging population in India is increasing due to better medical facilities and early diagnosis of disease. This also increases the age related UTIs in men due to BPH and females too due to hormone related changes. These people are to be treated well as they are underprivileged physically and monetarily. Another issue that we all face is the increasing trends of nosocomial infections which constitute about 40% of the total infections. With the constantly changing spectrum of organisms and the varied antibio­grams, we as clinicians are perpetually flummoxed in selecting appropriate treatment protocols. Add to it the ever increasing use of higher antibiotics at the primary care level leading to early antibiotic resistance and leaving us with very little scope for subsequent treatment. Another vexing problem is lack of application of the current existing guidelines which confuses the issue even further. We all know that episodes of UTI can be effectively managed and treated with antibiotics. This book helps attract the attention towards the present scenario in UTI in various fields. This starts right from microbiology labs to the ICU setting. The current Update on Urinary Tract Infections is about solving clinical problems that we face daily in treating urinary tract infections. Authors here have reviewed the current literature and tried to update the subject of UTI under various important categories. This actually is an evidence-based book on UTI which has been continuously updated over the last 10 years.

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Update on Urinary Tract Infections

In this book, authors have concisely compiled the current research and updates on the subject, presenting it as a readyreference which can be easily used by all clinicians for updating their knowledge for the future. Such knowledge gives the readers information helping them to reconsider and optimise their own ways of treating the problem.

Dr Naresh Trehan Chairman and Managing Director Medanta—The Medicity Gurugram, Haryana, India

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Preface Urinary tract infection (UTI) is one of the most common problems faced by all physicians in the community or the hospital. Over the past many years there has been a shift in the understanding of UTI. The field continues to be fertile subject for both basic science and clinicians. The way of looking at UTI has changed over time but many old ways still remain. I have asked the authors to identify the most relevant clinical questions in their subspeciality, perform schematic literature search and apprise the reader about the same. Interestingly, our paradigms continue to change. I hope this book represents the most comprehensive discussions of UTI. The techniques and technologies illustrated do represent the most popular, well utilised and enduring management options of today. I hope the readers find this issue provocative, informative and very applicable in managing their patients of UTI.

Rakesh Khera

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Acknowledgments All my teachers who have taught me new things to keep me abreast of the situation in medical science. My family (Saloni, Shagun, Suhani & OSCAR), parents and my friend (Dr Prasun Ghosh) were all very instrumental in their help. My special thanks to my daughter Shagun Khera who drew the bacterial image on the cover of this book. Every journey begins with a step and this editorship is a first one for me. I hope it brings more good work for me.

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Contents 1. Genitourinary Tuberculosis

1

Varun Mittal, Jamaluddin, Rajat Arora, Rakesh Khera

• Etiology 1 • Pathophysiology 1 • Diagnosis 3 • Investigations 3 • Treatment 8 •  Medical Care  9 •  Newer Drugs 10 •  Surgical Management 11 •  Genitourinary Tuberculosis in Carcinoma Bladder  12 2. Fungal Urinary Tract Infections

15

Rishi Nayyar, Siddharth Yadav

• Epidemiology 16 • Pathogenesis 17 • Diagnosis 18 • Management 23 •  Aspergillus Urinary Tract Infection 25 • Mucorales 27 3. Emphysematous Pyelonephritis

32

Prashant Mulawkar

•  Associated Factors 32 • Etiology 33 • Pathogenesis 33 • Classification 34 •  Clinical Presentation 37 •  Histopathology Findings 39 •  Diagnostic Criteria 39 • Management 41 •  Medical Management 43 •  Special Conditions 45

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Update on Urinary Tract Infections

4. Urinary Tract Infection in Intensive Care Unit

50

Chitra Mehta

•  Risk Factors 52 • Pathogenesis 53 • Microbiology 54 •  Clinical Presentation 55 • Diagnosis 55 •  Blood Cultures 56 •  Inflammatory Markers 56 •  Diagnostic Imaging 56 • Complications 57 • Management 57 •  Urine Culture and Catheter Replacement before Treatment 58 •  Antimicrobial Therapy 58 •  Asymptomatic Bacteriuria 60 •  Fungal Urinary Tract Infection 60 • Prevention 61 5. Recurrent Urinary Tract Infection in Elderly Female

66

Anup Kumar, Niraj Kumar

•  Risk Factors 66 • Diagnosis 67 • Treatment 68 •  Prevention of Recurrent Urinary Tract Infection 69 6. Asymptomatic Bacteriuria

74

Pankaj N Maheshwari, Olajide O Abiola, Vinayak Wagaskar

• Epidemiology 74 • Pathophysiology 75 •  Predisposing Factors 76 •  Microbiology of Asymptomatic Bacteriuria 76 • Pathogenesis 77 • Diagnosis 78 •  Screening and Treatment 80

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Contents

7. Urinary Tract Infection in Renal Transplant Patients

xix

87

Prasun Ghosh, Anil Sharma, Vijay kher

•  Etiologic Agents 87 •  Risk Factors 87 •  Site of Infection 87 •  Clinical Presentation 88 • Diagnosis 88 •  General Measures 88 • Treatment 89 •  Atypical Infections 90 •  Recurrent Urinary Tract Infection 91 8. Catheter-associated Urinary Tract Infections

94

Varun Mittal, Jamaluddin, Rakesh Khera

• Incidence 94 • Etiology 95 • Presentation 96 • Evaluation 97 • Management 98 •  Prevention of Catheter-associated Urinary Tract Infections 100 9. Multidrug-Resistant Urinary Tract Infection

111

Sushil Bhatia

• Prevention 114 • Treatment 119 10. Vaccines for Urinary Tract Infection

124

Sohrab Arora, Ashwin Mallya

•  Pathogenesis of Urinary Tract Infections 124 •  Vaccination Strategies 126 •  The Way Ahead 129 11. Bacterial Biofilms

134

Nikhil Khattar, Arif Akhtar

•  What is a Biofilm? 134 •  Why Biofilms are Formed? 136

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Update on Urinary Tract Infections

•  Architecture and Genesis of Biofilm 138 •  Biofilms in Urinary Tract Infections 140 •  Biofilms Phenotype 141 • Diagnosis 145 •  Treatment of Biofilms Infection 147 12. Urinary Tract Infection and Bacterial Virulence

159

Pratibha Narang, Udit Narang

•  Concept of Significant Bacteriuria 160 •  Pathogenesis and Bacterial Virulence 162 •  Bacterial Virulence 165 •  Future Consideration 174 13. Radiology of Urinary Tract Infections

179

TBS Buxi, Anurag Yadav, Swapnil Sheth

•  Plain Radiograph of Kidney, Ureter, and Bladder 179 •  Intravenous Urography 180 •  Micturating Cystourethrography and Retrograde Urethrogram 180 • Ultrasonography 182 •  Computed Tomography 183 •  Magnetic Resonance Imaging 184 • Pathologies 185 Index 203

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CHAPTER

1

Genitourinary Tuberculosis

Varun Mittal, Jamaluddin, Rajat Arora, Rakesh Khera

INTRODUCTION An estimated 4–20% of individuals with pulmonary tuberculosis (TB) develop genitourinary involvement, mostly in developing countries.1,2 In patients with miliary disease, 25–62% have been documented to have concomitant renal lesions.3

ETIOLOGY The most common pathogen associated with TB is Mycobacterium tuberculosis. Uncommonly implicated pathogens include Mycobac­ terium kansasii, Mycobacterium fortuitum, Mycobacterium bovis, Mycobacterium avium-intracellulare and Mycobacterium xenopi.

PATHOPHYSIOLOGY Generally primary infection is in the form of pulmonary TB. Gen­ito­ urinary tract is believed to be involved secondarily. Clinical symp­ toms usually develop 10–15 years after the primary insult.

Kidney Kidney is usually infected by hematogenous spread of bacilli from a primary focus of infection. Mycobacterial seeding leads to granu­ loma formation in proximity to glomeruli which may heal with fibro­ sis or may caseate and rupture into the tubular lumen.4,5 Dest­ruction of renal papilla can lead to calyceal ulceration or abscess formation. Involvement of the collecting system may result in fib­rotic scarring and stenosis with calcification and called “putty kidney”.

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Ureter Tuberculous ureteritis is always an extension of the disease from the kidney. It often causes ureteral strictures and hydronephrosis. The most common site is the lower third of ureter. Rarely, a panureteric stricture takes the form of corkscrew or pipe stem ureter.

Bladder Bladder lesions are without exception secondary to renal TB. The earliest forms of infection start around one or another ureteral ori­ fice. It initially manifests as superficial inflammation with bullous edema and granulation. Fibrosis of the ureteral orifice can lead to stricture formation with hydronephrosis or scarring (i.e. golf-hole appearance) with vesicoureteral reflux. Severe cases involve the entire bladder wall, where deep layers of muscle are eventually replaced by fibrous tissue, thus producing a thick fibrous bladder with progressive reduction of bladder capac­ ity (thimble bladder).

Prostate Prostatic TB is also the result of hematogenous spread, but involve­ ment is rare. In many cases, pathologists diagnose it incidentally after transurethral resection of the prostate (TURP). On digital rectal examination, it feels like a firm granulomatous nodule, and needs to be differentiated from malignancy. Very rarely, in acute fulminating cases, it spreads rapidly and presents as perianal sinus.

Epididymis and Testis In children, it is hematological spread, while in adults it seems to direc­tly spread from the urinary tract through the retrograde route. The formation of a draining sinus is uncommon in developed countries, but epididymal induration and beading of the vas are common. Involvement of the testis is usually due to direct exten­ sion. Infertility may result from bilateral vasal obstruction. Nodular beading of the vas is a characteristic physical finding. Orchitis and the resulting testicular swelling can be difficult to differentiate from other mass lesions of the testes.

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Chapter 1: Genitourinary Tuberculosis

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DIAGNOSIS Symptoms The presentation is often vague, and physicians must have a high degree of awareness to make the diagnosis. Symptoms are generally chronic, intermittent, and nonspecific. The most common symptoms are urinary frequency, urgency, dysuria, suprapubic pain, blood or pus in the urine, and fever. Urinary urgency is unresponsive to all treatment when the bladder is extensively involved. Painless gross and microscopic hematuria occurs in approximately 10% and 5% of cases. Unexplained infertility in both men and women may be attributable to genitourinary tuberculosis (GUTB).

Examination Physical examination is typically unremarkable. Tender testicular or epididymal swelling, nodularity and beading of the spermatic cord and vas may be the most telltale physical signs of GUTB one can find. In late cases, epididymocutaneous sinus formations may develop. Nodularity over the surface of prostate may be felt on dig­ ital rectal examination.

INVESTIGATIONS The diagnosis of GUTB is established by demonstration of tuber­ cle bacilli in the urine; the constellation of dysuria, sterile pyuria, hematuria, and characteristic radiographic findings are highly sug­ gestive of the diagnosis.6 In the absence of alternative explanation for persistent sterile pyuria, 3–6 urine cultures for acid-fast bacilli (AFB) should be performed (regardless of perceived risk for TB) together with radiography.

Purified Protein Derivative Tuberculin As many as 88% of persons with GUTB have been documented to have a positive purified protein derivative (PPD);7 one study includ­ ing 100 women with laparoscopically confirmed infection noted a sensitivity and specificity of 55% and 80%, respectively.8

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Update on Urinary Tract Infections

Interferon-gamma Release Assays There are few data evaluating the utility of interferon-gamma release assays (IGRAs) for diagnosis of GUTB. In one study including 111 Chinese patients with extrapulmonary disease and 8 with GUTB, the sensitivity and specificity of the T-spot IGRA test was 100% and 67%, respectively.9

Urine Studies Acid-fast Bacillus Smear Tuberculous bacilli are shed into the urine intermittently, and AFB smear is often negative since the cutoff for a positive smear is 5,000 organisms per milliliter. Serial early-morning urine collection (at least 3) is a specific (89–96%) but less sensitive (approximately 52%) tool.

Acid-fast Bacillus Urine Cultures It is still considered the criterion standard for evidence of active disease, with sensitivity of 65% and specificity of 100%. Between 11% and 80% of single urine specimens are positive for AFB cul­ ture in patients with active disease, depending on the demographic group and stage of infection.10 Therefore, 3–6 first morning mid­ stream specimens should be obtained for AFB culture to maximize the likelihood of a positive result. Every effort should be made to process the samples immediately after collection. Sending cultures before starting antitubercular treatment and adjusting therapy according to sensitivity in case of resistance is always recommended. The following culture methods are available: • Solid media: The Lowenstein-Jensen medium yields results in more than 4 weeks. • Radiometric media: The BACTEC 460 medium yields results in 2–3 days. Identification of acid-fast organisms in the urine sediment via Ziehl-Neelsen stain or fluorescent dye techniques is not diagnos­ tic for TB, since nonpathogenic mycobacteria may be present.

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False-negative results may occur in the setting of concomitant anti­ tuberculous or antibacterial therapy capable of inhibiting mycobac­ terial growth (particularly fluoroquinolones).

Polymerase Chain Reaction The polymerase chain reaction (PCR) test has been extensively studied and has been proven highly sensitive, specific, and rapid. In various studies, data show sensitivity ranging from 87% to 100% (usually >90%) and specificity from 92 to 99.8% (usually >95%).11,12 Compare this with cultures (37%), bladder biopsies (47%), and intravenous urography (IVU) examinations (88%). Along with an accurate clinical assessment, PCR is the best tool available for avoi­ ding a treatment delay because results are available in only about 6 hours. The following PCR tests are available with near-equivalent quality: • Genus-specific 16S ribosomal ribonucleic acid (rRNA) PCR test • Species-specific IS6110 PCR test • Roche Amplicor M. tuberculosis PCR test • Amplified M. tuberculosis Direct Detection Test (AMDT) Tuberculous Peptide Nucleic Acid Fluorescence in situ Hybri­di­ zation Fluorescence in situ hybridization (FISH) using peptide nucleic acid (PNA) probes allows differentiation between tuberculous and nontuberculous mycobacteria in smears of mycobacterial cultures. PNA molecules are pseudo-peptides with deoxyribonucleic acid (DNA)-binding capacity in which the sugar phosphate backbone of DNA has been replaced by a polyamide backbone.

Nucleic Acid Amplification Nucleic acid amplification allows both detection and identification of M. tuberculosis through enzymatic amplification of bacterial DNA. The most widely used technique is PCR, but transcription mediated amplification (TMA) and strand displacement amplifica­ tion (SDA) are also commercially used. The sensitivity of this test is higher than that of smear microscopy but it is slightly lower than that of culture techniques. The main advantage of these tests is that they offer quick results, paired with a high level diagnostic accuracy.

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Update on Urinary Tract Infections

Some individual laboratories offer validated testing, although, thus far, there is no commercial nucleic acid amplification test approved by the US Food and Drug Administration (FDA) for detection of mycobacterial nucleic acid in urine.

Transcription-Mediated Amplification/ Amplified M. tuberculosis Direct Test Transcription-mediated amplification can identify the presence of genetic information unique to M. tuberculosis directly from preproc­ essed clinical specimens. Amplified M. tuberculosis Direct (MTD) test (Gen-Probe, Hologic) detects M. tuberculosis rRNA directly and rapidly, with sensitivity similar to that of culture techniques. The sensitivity of this test is of 96% and its specificity is 100% for M. tuberculosis on specimens that are smear-positive for acid-fast bacilli. One other disadvantage of the technique is that positive results are recorded for both viable and dead bacilli.

GeneXpert M. tuberculosis Direct/RIF Molecular System It detects DNA sequences specific for M. tuberculosis and rifam­ picin resistance by polymerase chain reaction. Data on use of the GeneXpert for diagnosis of extrapulmonary TB are limited. One study of 91 urine samples from patients with suspected TB or non­ tuberculous mycobacteria infections (including five culture positive samples) noted sensitivity and specificity of 100 and 98.6%, respec­ tively.13 It simultaneously detects TB and rifampin drug resistance. It provides accurate results within 2 hours. It has been strongly recom­ mended by World Health Organization (WHO) for use in diagnosis of TB since December 2010. TBXpert Project was launched in 2013 by WHO to provide equipment to 21 countries for rapid detection of TB and rifampin resistance.

Imaging Studies X-ray Chest and spine radiographs may show old or active lesions. However, chest radiographic findings are negative in 50% cases.

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Chapter 1: Genitourinary Tuberculosis

7

KUB radiographs reveal calcifications in the kidney and ureter in approximately 50% of patients. Calcifications are intraluminal, as opposed to schistosomiasis, which produces intramural calcifica­ tions.

Intravenous Urography It remains the standard diagnostic imaging studies for renal TB and has 88–95% sensitivity. Approximately 10–15% of patients who present with active renal TB will have normal urographic findings.14 The earliest radiographically detectable changes are cavitary lesions that progress to the papilla and invade the collecting system, causing calyceal disruption. Findings of infundibular stenosis and multiple ureteral strictures are highly suggestive of renal TB. Later findings may include calcifications, scarring and stricture formation (Table 1).15

Ultrasonography High-resolution transrectal ultrasonography (TRUS) has become a very useful noninvasive technique. TRUS can reveal abnormalities in the seminal vesicles and ejaculatory duct and can help assess the status of the prostate.

Computed Tomography Scan This imaging test is increasingly being used as the primary modality of investigation in disorders of the genitourinary tract. It is a highly sensitive to detect disease in early stage. It is a useful adjunct to IVP and is helpful in late or advanced disease for assessing the extent of disease.16,17 Advantages over intravenous urography: Depicts the extent of extrarenal spread of infection.

Important Tool Retrograde Pyelography It is rarely indicated now except in patients with renal failure in whom the kidneys cannot excrete contrast and to evaluate stricture in the upper urinary tract. It also helps for sampling urine from individual kidneys for microbiology.

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Update on Urinary Tract Infections Table 1: Intravenous urography findings in urinary tuberculosis. • Kidney Ureter • Distorted calyces • Mucosal irregularities • Moth eaten appearance of calyces • “Pipe-stem” ureters • Papillary necrosis • Strictures • Decreased contrast enhancement • Dilated ureters -- Phantom calyx • Beaded appearance/“Cork screw” ureter -- Autonephrectomy Bladder • Dilated calyx or entire PCS • Mucosal irregularity, decreased capacity • Kerr’s kink • “Thimble” bladder

Cystoscopy and Bladder Biopsy • Rarely indicated: ▪▪ Assessing the extent of the disease ▪▪ Response to chemotherapy ▪▪ To rule out acute interstitial cystitis. • Cystoscopy: ▪▪ Bladder filling under direct vision ▪▪ Under general anesthesia with a muscle relaxant reduces the risk of hemorrhage. • Biopsy: ▪▪ Only to rule out malignancy ▪▪ Not prior to initiation of medical Rx.

Fine Needle Aspiration Fine needle aspiration (FNA) as a minimally invasive technique plays a prime role in the diagnosis of tubercular epididymitis and epididymo-orchitis. AFB may be detected on FNA smears in up to 60% of these patients.

TREATMENT “End TB strategy” was adopted by the World Health Assembly in May 2014. It outlines global impact targets to reduce TB deaths by 90%, to cut new cases by 80% between 2015 and 2030.

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MEDICAL CARE Treatment with standard antituberculous agents for 6 months is generally successful in eradicating active renal infection due to drug-susceptible TB.18 The treatment regimen varies with whether or not the patient has HIV infection or drug-resistant TB. GUTB responds better to a short course of treatment than pulmonary TB because GUTB carries a lower mycobacterial load. Also, ison­ icotinic acid hydrazide (INH) and rifampin penetrate well into the cavi­tary lesions associated with GUTB. A high concentration of INH, rifampin, and pyrazinamide are maintained in urine. The primary aims of treatment are to preserve renal parenchyma and function, to make the patient noninfectious, and to manage comor­ bid conditions. Urine sterilization generally occurs within 2 weeks of initiating therapy. In one study including seven patients with culture-confirmed urinary tract disease treated with standard therapy, no relapse was observed.19 Relapse rates among patients who require nephrec­ tomy appear to be relatively low; one large study noted a relapse rate 3 g/L) in 79%, 13% and 21% patients, respectively.3

Gas Analysis Huang and Tseng3 performed radiology guided needle aspiration of the gases released by EPN tissues. They found carbon dioxide and hydrogen to be the main constituents. Nitrogen and oxygen have also been found along with traces of ammonia, methane, and carbon monoxide. The gas samples did not contain oxygen containing hydrocarbons (e.g. alcohol, aldehydes and organic acids) or sulfur containing compounds.

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Chapter 3: Emphysematous Pyelonephritis

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HISTOPATHOLOGY FINDINGS Histopathology showed a varying combination of following findings:3 Impairment of tissue circulation (infarction, vascular thrombosis, arteriosclerosis, and glomerulosclerosis), acute inflammatory cell infiltration with focal necrosis and abscess formation, interstitial hemorrhage, chronic pyelonephritis, empty spaces (because of gas formation), diabetic nephropathy (glomerulosclerosis, several Kimmelstiel-Wilson nodules, and hyalinized arteriosclerosis).

DIAGNOSTIC CRITERIA Huang Tseng3 used following diagnostic criterion for EPN: • Symptoms and signs of upper UTI, or fever with a positive urine culture or pyuria without other identified infectious foci • Radiological evidence by CT scan of gas accumulation in the collecting system, renal parenchyma, or perinephric or pararenal space • No fistula between the urinary tract and bowel • No recent history of trauma, urinary catheter insertion, or drainage.

Radiology Emphysematous pyelonephritis is primarily a radiological diagnosis. Most of the clinical findings and laboratory parameters are nonspecific and are indicative of sepsis of renal origin. It is the presence of gas seen on radiology which clinches the diagnosis of EPN.

Conventional Radiology (Plain X-ray, Kidney Ureter and Bladder and Intravenous Pyelogram) Langston and Pfister22 described three main radiographic patterns. The earliest sign is diffuse mottling of the renal parenchyma. Bubbly renal parenchyma (Fig. 5) surrounded by a crescent of gas [peri­ nephric space (Fig. 6)] is suggestive of further deterioration suggesting renal necrosis. Extension through Gerota’s fascia is seen as gas in retroperitoneal space and even extending up to posterior thoracic wall. However mottled gas and crescent formation are not frequently found, seen in 22% and 15% of cases only respectively.10

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Fig. 5: KUB X-ray showing bubbly renal parenchyma. Courtesy: Dr Vivek Birla.

Fig. 6: KUB X-ray showing bubbly renal parenchyma surrounded by crescent of gas.

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The most common radiological finding is gas collection in renal parenchyma and perirenal tissues. An IVP would demonstrate nonfunctioning affected kidney in 45% of cases.10 IVP may also show persistent nephrogram on affected side due to delayed excretion of contrast material.23 However in view of known hazardous complications of IVP especially in these sick diabetic sick patients, these investigations are not routinely carried out.

Ultrasonography23,24 Ultrasonography (USG) cannot accurately measure depth of gas collection. Ultrasonography findings are: an enlarged kidney containing high-amplitude echoes within the renal parenchyma, low-level posterior dirty acoustic shadowing. The depth of parenchymal involvement may be underestimated at USG. Multiple renal stones may also manifest as echogenic foci without clean acoustic shadowing.23

Computed Tomography Scan Computed tomography is the best modality to detect gas and to assess the extent of the disease. It is more sensitive. CT scan is necessary for early diagnosis and further management of EPN. It is helpful in identifying and localizing gas in the renal parenchyma; the subcapsular, perinephric, or pararenal space; the collecting system; or occasionally the vascular system.25 Both the classification systems currently in vogue are based on CT scan only.

Magnetic Resonance Imaging Computed tomography with contrast agents cannot be performed in patients with renal failure. Diffusion-weighted magnetic resonance imaging (DW-MRI) has the potential to overcome this disadvantage. However, CT is more useful for the diagnosis of renal calculi and EPN.26

MANAGEMENT If any patient with pyelonephritis, whether diabetic or not, fails to respond to standard line of pyelonephritis treatment, should undergo urgent CT scan to confirm EPN.

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Basic Resuscitation • Intravenous fluids to maintain systolic blood pressure above 100 mm Hg systolic, and if required inotropic support • Oxygen • Acid-base balance correction • Good glycemic control • Appropriate antibiotics.

Empirical Initial Antimicrobial Therapy27 Although EPN is a surgical emergency, empirical antibiotic therapy plays a vital role in the initial management. In majority of the patients the culture reports are not available and one has to rely on first-line empirical antibiotic therapy. Preferred single-agent options for treating EPN, effective against the highest percentage of bacterial isolates, are third- or fourth-generation cephalosporins (e.g. ceftazidime) and carbapenems. Alternate empiric regimens include a combination of amikacin and third-generation cephalosporin, given the very low overall resistance rates among E. coli, Klebsiella pneumoniae, and P. mirabilis. In patients who have been hospitalized and treated with antibio­ tics within the past year, who need emergency hemodialysis, or who have developed disseminated intravascular coagulation (DIC), it is likely that a third-generation cephalosporin-resistant pathogen is invol­ved. Hence, empiric carbapenem treatment should be considered. Resistance of uropathogens to fluoroquinolones is increasing.27 Risk factors for fluoroquinolone-resistant E. coli infection include recent hospitalization prior fluoroquinolone use, and urinary catheter placement. Consequently, fluoroquinolones should be avoided as empiric treatment of EPN, given any of the risk factors above. Indiscriminate use of fluoroquinolones for complicated or catheterrelated UTI may even undermine the susceptibility of respiratory pathogens to these agents. However, this does not mean that quinolones should not be used. The most common causative organisms are gram-negative bac­teria. Initial therapy should target them. Aminoglycosides, beta-lactamase inhibitors, cephalosporins, and quinolones can be used. This is usually guided by local hospital policy.16 Once the culture report is available, the antibiotics can be chan­ged.

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MEDICAL MANAGEMENT Medical management (MM) alone is rarely used in EPN, because it is associated with high failure rates. Mortality rates with MM alone have been reported as 40%3 and 50%.5 Nowadays EPN gets picked up early on CT scan showing very small air pockets. Such patients are more likely to respond to MM alone. In class 1 and class 2 EPN (based on Huang and Tseng classification) MM alone or combined with PCD can be used. There have been reports of successful management of EPN by MM alone. Chauhan28 reported a case of Class 3A EPN managed with MM alone as patient was not willing for operative intervention. However, in this case, the patient had a small renal calculus and minimal perinephric gas. Kolla29 reported a series of eight patients with EPN, four of these were managed with MM alone. These patients were in Class 1, 2, 3A and 4 each. Two of these received imipenem and two cefoperazone + sulbactam. Flores30 reported a case of class 4 (bilateral) EPN managed by MM alone.

Percutaneous Drainage Percutaneous drainage (PCD) should be the part of initial management strategy for EPN.5 Fluoroscopy guided drainage of EPN was first described by Hudson et al. in 1986.31 The technique of the CT guided PCD is described by Chen.32 PCD enables a mini­ mally invasive therapy allowing maximum nephron sparing. In a meta-analysis reported by Somani5 ten retrospective studies on 210 EPN patients have been reported. Mortality was significantly less in patients undergoing PCD in comparison to other treatments like MM alone and MM combined by emergency nephrectomy. The combined nephron sparing rate in some studies was 70%. This is especially advantageous in bilateral EPN. Some patients may need more than one catheter. Repeat CT after 4–7 days may be needed in some patients to look for other non-communicating air/fluid collections. If some patients have prolonged fever and sepsis, they would need elective nephrectomy. Widespread adoption of PCD has been the important factor leading to decline in the mortality due to EPN.

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Thrombocytopenia, disturbance of consciousness, acute renal function impairment and shock at initial presentation are the four risk factors predicting poor response to PCD plus antibiotics. Class 3 or class 4 EPN patients with two or more of these risk factors would have significantly higher failure rate of PCD than those with no or only one risk factor.3

Double J Stent Patients developing EPN due to ureteric obstruction either because of calculi or sloughed papilla can be managed by Double J (DJ) stent. DJ stenting can be done under local anesthesia and has less morbidity as compared to PCD. However, literature about DJ stenting is scant. Kolla29 reported a series of eight patients with EPN, four of these were managed with DJ stenting alone. Das33 reported a series of 15 patients, wherein seven patients underwent DJ stenting and four underwent PCD. There was no mortality.

Emergency Nephrectomy and Delayed Nephrectomy Until 1980, emergency nephrectomy and/or open surgical drainage (and antibiotics) was the most accepted treatment of EPN with a reported mortality rate of 40–50%. It was the gold standard treatment in past. Nephrectomy is still the favored treatment for extensive disease. Nephrectomy can be the best management option in extensive EPN with fulminant course.3 In Huang3 series, nephrectomy had overall success rate of 90%. Nine out of 10 patients survived. Of these two were emergency nephrectomy (EN); both survived. Eight were delayed nephrectomy (DN) for PCD failures and seven survived. Recently this therapy has been questioned because of high mortality. EN might not be the first-line of treatment even in severe cases.34 The author goes to the extent that there is no place for immediate nephrectomy. However, the poor outcome in nephrectomy group may not be because of that treatment option but to late detection and multiple comorbidities these patients had.35 Laparoscopic nephrectomy for EPN has also been reported.36,37

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Risk Factors Affecting Mortality Falagas38 in a meta-analysis of seven studies from 1965 to 2006 reported the factors associated with mortality in EPN. Overall mortality in this meta-analysis was 25% (range from 11 to 42%). The significant risk factors associated with mortality were: conservative mode of treatment alone, bilateral EPN, type I EPN (Wan classification) and thrombocytopenia. Conservative mode of treatment included fluid resuscitation, antibiotics and diabetes control. It did not include PCD. In addition, systolic blood pressure less than 90 mm Hg, serum creatinine greater than 2.5 mg/dL, disturbance of consciousness, as well as increase in serum creatinine (>0.5 mg/dL or >1 mg/dL, if baseline serum creatinine level of the patient was 3 mg/dL, respectively) were found to be associated with higher mortality.3 In another review18 patients without obstructive uropathy, patients undergoing nephrectomy were at increased risk of mortality. On the other hand following factors were not associated with mortality: diabetes, nephrolithiasis, E. coli or K. pneumoniae etio­logy, age more than 50, female sex, side of the EPN, diabetes not controlled, blood pressure less than 100 mm Hg, history of UTIs, alcoho­ lism, proteinuria, bacteremia, retinopathy and macrohematuria.38

SPECIAL CONDITIONS Emphysematous Pyelonephritis and Pregnancy Pregnancy is not considered a risk factor for EPN although UTIs are common during pregnancy. A case of bilateral EPN in postpartum period has been described.39

Bilateral Emphysematous Pyelonephritis Bilateral EPN accounts for around 10% cases of EPN. It is associated with significant mortality. Bilateral nephrectomy is usually avoided because this would render the patient anephric requiring lifelong renal replacement therapy. Successful management of bilateral EPN with40 PCD, or without41 PCD antibiotics and medical therapy has been described.42

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Emphysematous Pyelonephritis with Xanthogranulomatous Pyelonephritis Xanthogranulomatous pyelonephritis (XGPN) accounts for less than 1% cases of histologically proven chronic pyelonephritis. EPN complicating XGPN is very rare. All the reported patients were female. These patients need nephrectomy.43

Emphysematous Pyelonephritis in Transplanted Kidney Emphysematous pyelonephritis is an infrequent infection in renal allograft. Al-Geizawi44 has proposed a new classification for the same. Patients with gas in collecting system only would need aggressive medical therapy with relief of obstruction, if any. In a patient with gas replacing less than 50% of renal parenchyma, minimum spread to the surrounding tissues and rapidly controlled sepsis would need aggressive MM, PCD and follow-up imaging. Whereas a patient with gas replacing more than 50% of renal parenchyma; or extensive spread of infection in the perinephric area; or patient with evidence of multiple organ failure, uncontrolled sepsis, or shock not responding to medical treatment would be best served by allograft nephrectomy.45

Emphysematous Cystitis Emphysematous cystitis46 is less common than EPN. It is most often found in diabetic females in sixth and seventh decade. Escherichia coli is the most common pathogen. Concurrent emphysematous infec­ tion of other organs is seen in 15.4% cases in this series. Of these concurrent infections EPN is the most common. Most cases are managed conservatively. Only the more advanced cases needing surgical treatment. It is less life-threatening than EPN.

REFERENCES 1. Kelly HA, MacCallum WG. Pneumaturia. JAMA. 1898;31:375-81. 2. Schultz EH Jr, Klorfein EH. Emphysematous pyelonephritis. J Urol. 1962;87:762-6. 3. Huang JJ, Tseng CC. Emphysematous pyelonephritis: clinical radiological classification, management, prognosis, and pathogenesis. Arch Intern Med. 2000;60:797-805.

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4. Wan YL, Lee TY, Bullard MJ, et al. Acute gas-producing bacterial renal infection: correlation between imaging findings and clinical outcome. Radiology. 1996;198:433-8. 5. Somani BK, Nabi G, Thorpe P, et al. Is percutaneous drainage the new gold standard in the management of emphysematous pyelonephritis? Evidence from a systematic review. J Urol. 2008;179:1844-9. 6. Huang JJ, Chen KW, Ruaan MK. Mixed acid fermentation of glucose as a mechanism of emphysematous urinary tract infection. J Urol. 1991;146:148-51. 7. Shokeir AA, El-Azab M, Mohsen T, et al. Emphysematous pyelonephritis: a 15-year experience with 20 cases. Urology. 1997;49(3):343-6. 8. Dubey IB, Agrawal V, Jain BK, et al. Emphysematous pyelonephritis in a non-diabetic patient with non-obstructed kidney: an unknown entity. Saudi J Kidney Dis Transpl. 2013;24(1):97-9 9. Ravikumar YS, KM Srinath, Adarsh LS, et al. Emphysematous pyelonephritis in a non-diabetic young woman: A Rare association. JIACM. 2012;13:328-9. 10. Michaeli J, Mogle S, Perlberg S, et al. Emphysematous pyelonephritis. J Urol. 1984;131:203-7. 11. Mohamed Ashif PA, Sandeep P, Sasidharan PK. Emphysematous pyelonephritis in a patient infected with the human immunodeficiency virus. Saudi J Kidney Dis Transpl. 2012;23:1046-50. 12. Bansal RK, Lambe S, Kapoor A. Emphysematous pyelonephritis in failed renal allograft: Case report and review of literature. Urol Ann. 2016;8:111-3. 13. Godec CJ, Cass AS, Berkseth R. Emphysematous pyelonephritis in a solitary kidney. J Urol. 1980;124:119-21. 14. Lin CH, Huang JJ, Liu HL, et al. Lin, Renal cell carcinoma complicated by emphysematous pyelonephritis in a non-diabetic patient with renal failure. Nephron. 2002;92:227-9. 15. Kumar N, Singh NP, Mittal A, et al. An uncommon cause of postpartum renal failure—bilateral emphysematous pyelonephritis. Ren Fail. 2009;31:171-4. 16. Ubee SS, McGlynn L, Fordham M. Emphysematous pyelonephritis. BJU Int. 2010;107:1474-8. 17. Tang HJ, Li CM, Yen MY, et al. Clinical characteristics of emphysematous pyelonephritis. J Microbiol Immunol Infect. 2001;34:125-30. 18. Aboumarzouk OM, Hughes O, Narahari K, et al. Emphysematous pye­l­o­nephritis: Time for a management plan with an evidence-based approach. Arab J Urol. 2014;12:106-15. 19. Hong MY, Chan TY, Chi CH, et al. Scrotum balloon: an unusual presentation of emphysematous pyelonephritis. QJM. 2011;104:447-8. 20. Narlawar RS, Raut AA, Nagar A, et al. Imaging features and guided drain­age in emphysematous pyelonephritis: a study of 11 cases. Clin Radiol. 2004;59:192-7.

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Update on Urinary Tract Infections 21. Modi P, Goel R, Dodia S. Scrotal extension of emphysematous pyelonephritis. Int Urol Nephrol. 2007;39:405-7. 22. Langston CS, Pfister RC. Renal emphysema. A case report and review of the literature. Am J Roentgenol Radium Ther Nucl Med. 1970;110:778-86. 23. Grayson DE, Abbott RM, Levy AD, et al. Emphysematous infections of the abdomen and pelvis: a pictorial review. Radiographics. 2002; 22:543-61. 24. Best CD, Terris MK, Tacker JR, et al. Clinical and radiological findings in patients with gas forming renal abscess treated conservatively. J Urol. 1999;1273-6. 25. Kawashima A, Sandler CM, Goldman SM, et al. CT of renal inflammatory disease. Radiographics. 1997;17:851-66. 26. Rathod SB, Kumbhar SS, Nanivadekar A, et al. Role of diffusion-weigh­ ted MRI in acute pyelonephritis: a prospective study. Acta Radiol. 2015;56:244-9. 27. Lu YC, Hong JH, Chiang BJ, et al. Recommended Initial Antimicrobial Therapy for Emphysematous Pyelonephritis: 51 Cases and 14-YearExperience of a Tertiary Referral Center. Medicine (Baltimore). 2016; 95:e3573. 28. Chauhan V, Sharma R. Emphysematous pyelonephritis (class IIIa) managed with antibiotics alone. Hong Kong Med J. 2015;21:363-5. 29. Kolla PK, Madhav D, Reddy S, et al. Clinical profile and outcome of conser­vatively managed emphysematous pyelonephritis. ISRN Urol. 2012;­2012:931982. doi: 10.5402/2012/931982. 30. Flores G, Nellen H, Magaña F, et al. Acute bilateral emphysematous pyelonephritis successfully managed by medical therapy alone: a case report and review of the literature. BMC Nephrol. 2002;3:4. 31. Hudson WA, Weyman PJ, van der Vliet AH, et al. Emphydematous pyelonephritis: successful management by percutaneous drainage. J Urol. 1986;136:884-6. 32. Chen MT, Huang CN, Chou YH, et al. Chen, Percutaneous drainage in the treatment of emphysematous pyelonephritis: 10-year experience. J Urol. 1997;157:1569-73. 33. Das D, Pal DK. Double J stenting: A rewarding option in the management of emphysematous pyelonephritis. Urol Ann. 2016;8:261-4. 34. Alsharif M, Mohammedkhalil A, Alsaywid B, et al. Emphysematous pyelonephritis: Is nephrectomy warranted? Urol Ann. 2015;7:494-8. 35. Kamarulzaman MN, Mohamed SK. RE: Emphysematous pyelonephritis: Is nephrectomy warranted? Urol Ann. 2016;8:258-9. 36. Bauman N, Sabbagh R, Hanmiah R, et al. Laparoscopic nephrectomy for emphysematous pyelonephritis. Can J Urol. 2005;12:2764-8 37. Justine Royle, Williamson R, Strachan M, et al. Emphysematous pyelonephritis successfully treated with laparoscopic nephrectomy. Br J Med Surg Urol. 2009;2:204-7.

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38. Falagas ME, Alexiou VG, Giannopoulou KP, et al. Risk factors for morta­ lity in patients with emphysematous pyelonephritis: a meta-analysis. J Urol. 2007;178:880-5. 39. Kumar N, Singh NP, Mittal A, et al. An uncommon cause of postpartum renal failure—bilateral emphysematous pyelonephritis. Ren Fail. 2009;31:171-4. 40. Misgar RA, Wani AI, Bashir MI, et al. Successful medical management of severe bilateral emphysematous pyelonephritis: case studies. Clin Diabetes. 2015;33:76-9. 41. Cheng ML, Nording H, Lim CH. Bilateral Emphysematous Pyelo­ nephritis with Hepatic Portal Venous Gas: Case Report. M-+alays J Med Sci. 2015;22:71-4. 42. Dutta D, Shivaprasad KS, Kumar M, et al. Conservative management of severe bilateral emphysematous pyelonephritis: Case series and review of literature. Indian J Endocrinol Metab. 2013;17:S329-32. 43. Wen YK, Chen ML. Xanthogranulomatous pyelonephritis complicated by emphysematous pyelonephritis in a hemodialysis patient. Clin Nephrol. 2007;68(6):422-7. 44. Al-Geizawi SM, Farney AC, Rogers J, et al. Renal allograft failure due to emphysematous pyelonephritis: successful non-operative management and proposed new classification scheme based on literature review. Transpl Infect Dis. 2010;12:543-50. 45. Bansal RK, Lambe S, Kapoor A. Emphysematous pyelonephritis in failed renal allograft: Case report and review of literature. Urol Ann. 2016;8:111-3. 46. Schicho A, Stroszczynski C, Wiggermann P. Emphysematous Cystitis: Mortality, Risk Factors, and Pathogens of a Rare Disease. Clin Pract. 2017;7(2):930.

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4

Urinary Tract Infection in Intensive Care Unit Chitra Mehta

INTRODUCTION Urinary tract infection (UTI) has been found to account for 25% of all cases of sepsis. It may be either community or hospital acquired. In intensive care unit (ICU), one may encounter both severe community acquired and/or a hospital acquired UTI. In a study in US, UTI accounted for 40% of patients presenting with septic shock to the emergency department (ED). It was found to be responsible for 25% of septic shocks due to hospital-acquired infections. Similarly, an Australian study found UTI to account for 30.2% of patients with septic shock being admitted in the ED. Urinary tract infection forms about 20–50% of all intensive care acquired infections. This is related to rampant use of indwelling catheters in these settings. Presence of indwelling catheter increases the risk of acquiring bacteriuria by 3–10% every day. Out of these about 10–25% patients develop UTI. The incidence of catheterassociated UTI (CAUTI) ranges from 2% to 6% in the first 10 days of catheterization. It is nearly 100% at 30 days of catheterization. Incidence of UTI in ICU has been observed to be approximately 7%. Catheter-associated UTI has been found to result in increased mortality, length of stay and healthcare costs. CAUTI prevention is an important patient safety goal, and is of vivid interest among ICU community. It is estimated that about 65–70% of CAUTIs are preventable. Indwelling catheter is considered as short-term if it remains in situ for less than 30 days. If the catheter indwelling time is more than 30 days, it is considered as long-term. In ICU, the catheter use is generally short-term.1-4

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DEFINITIONS Urinary tract infection is regarded as an inflammatory response to bacterial or fungal colonization of the urinary tract. Urinary tract infections can exhibit clinically in the form of uncomplicated urinary infection, complicated urinary infections, bacterial prostatitis and asymptomatic bacteriuria (ASB). The severity of infection depends upon the host response. Asymptomatic bacteriuria is said to be present if a specific amount of bacteria is isolated from an adequately collected urine sample in an asymptomatic patient. The prevalence of ASB has been found to range from 1% to 100% in general population. Data regarding prevalence of ASB in hospitalized patients is somehow lacking. Catheter-associated UTI needs to be defined with caution. It is difficult to differentiate between contamination, colonization, and true infection. More so in critically sick patients who are usually sedated, delirious or are unable to communicate. They may also not show typical signs and symptoms of UTI. Catheter-associated bacteriuria is defined as presence of significant bacteriuria (defined as bacterial counts of more than or equal to 105 CFU/mL in urine specimen obtained from catheter) irres­ pective of symptoms. CAUTI has been defined by presence of signi­ ficant bacteriuria from urine of a catheterized patient with signs and symptoms indicative of urinary infection. An ICU acquired UTI is defined by the presence of a positive urine culture on or later than Day 3 of ICU admission. Patients who develop positive urine culture within 48 hours of ICU discharge should also be considered as having ICU acquired UTI. Catheter-associated UTI has been defined by Infectious Diseases Society of America (IDSA) as the presence of symptoms and signs of urinary infection with no other attributable source, plus more than or equal to 103 CFU/mL of one or more bacterial species in a single catheter urine specimen. It is also said to be present if similar counts are obtained in midstream urine specimen of a patient who has got his catheter removed in previous 48 hours. Catheterassociated ASB (CA-ASB) is said to be present if more than or

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equal to 105 CFU/mL of one or more bacterial species is grown in a single catheter urine specimen in an asymptomatic patient. Catheter-associated funguria is defined by presence of fungus in a catheterized or recently catheterized patient. Fungal colony counts have not been found to have meaningful interpretation.5-7 However, some consider more than or equal to 104 CFU/mL an appropriate quantitative count for candiduria. So far it has been difficult to accurately establish relationship between CA-ASB and CAUTI. Majority of patients with CA-ASB do not develop CAUTI, and factors influencing this progression have not been identified. Investigators have been targeting CA-ASB prevention in the hope of bringing down the incidence of CAUTI.

RISK FACTORS Several factors have been found to be associated with bacteriuria. Many of them are important for critically sick patients especially CAUTI. Factors associated with risk of developing severe UTI have also been identified. These are enlisted in Table 1 and Box 1.4,8

Table 1: Risk factors for urinary tract infection. Modifiable

Nonmodifiable

Prolonged catheterization

Diabetes mellitus

Antibiotics before or upon admission

Elevated creatinine

Other active sites of infection

Female gender

Nonadherence to aseptic catheter care

Rapidly fatal underlying illness

Catheterization outside operation room

Old age

Nonadherence to closed drainage system

Prolonged estrogen deficiency

Instrumentation of urinary tract

Hemodialysis

Ureteric stents

Admission due to acute disorder

Rigorous monitoring of urine output

Immune alterations

Urology services Urinary retention Prolonged intensive care unit stay

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Box 1: Risk factors for severe urinary tract infection. • Healthcare associated infection • Female gender • Infection with multidrug-resistant organisms • Urinary obstruction • Prolonged urologic surgery • Mucosal trauma during catheterization • Cirrhosis • Prolonged intensive care unit length of stay • Immunosuppression • Structural urologic abnormalities • Old age

Intensive care unit acquired CAUTI has not been found to impact mortality, but is associated with significant morbidity. Risk factors for developing bacteremia secondary to UTI in ICU have been found to be renal disease, male sex and neutropenia. Suprapubic catheterization has similar rates of UTI when compared to urethral catheterization. Intermittent catheterization reduces the risk but does not eliminate it.

PATHOGENESIS In noncatheterized patients UTI occurs due to contamination with own fecal microflora. The flora colonizes the periurethral region and ascends up the urinary system. On the other hand, urinary catheterization is the most important predisposing factor for nosocomial UTI. It bypasses the host defense mechanisms and provides rapid access of organisms to the bladder. CAUTI may also result due to contamination from the hands of attending personnel during catheterization, or due to poor handling of the collection system. Extraluminally, microorganisms invade the bladder by moving upward in the mucus film coating the external surface of catheter. The biofilm formation, comprising of Tamm-Horsfall protein,

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organic molecules and electrolytes, protects uropathogens from antibiotics, urine flow and host defenses. Biofilm formation starts right after the catheter insertion, involving both interior and exterior surfaces. Biofilm formation has not been observed with synthetic materials. Intraluminal infection occurs secondary to contamination of the collecting bag, or failure to maintain closed drainage system. Both extraluminal and intraluminal routes of infection are important.9,10

MICROBIOLOGY Nosocomial UTIs have a wide range of infecting organisms, comm­ only antibiotic resistant when compared to community acquired uncomplicated UTI. Most of the catheter related infections are monobacterial (commonly, gram-negative bacilli, and enteroco­cci). Escherichia coli is the most common organism especially in community acquired UTI. Coagulase-negative Staphylococcus, ente­rococci, Candida species and non-fermenters like pseudomonas are frequently encountered in patients with indwelling catheter. Although multidrug-resistant organisms are more common in nosocomial UTI, extended spectrum B lactamases (ESBL) Enterobacteriaceae, and carbapenemases producing E. coli have been isolated in community acquired UTI as well. A study from Taiwan reported an incidence of 72% of ESBL producing E. coli and Klebsiella pneumoniae bacteremia due to urinary infection in patients admitted to ED. In ICU about 5–12% are polymicrobial UTIs. This usually occurs in presence of prolonged catheterization, neoplasm, stone, or in presence of fistula between vagina or bowel and the urinary tract. Incidence of gram-positive infections in ICU acquired UTI has been found to be 27.1%. There has been a recent increase in fungal UTIs with candiduria accounting for about one-third of ICU acquired UTI. Proteus mirabilis, Morganella morganii and Providentia species are common organisms in patients with chronic indwelling catheters. Isolation of Staphylococcus aureus in urine usually indicates a disseminated infection.11-13

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CLINICAL PRESENTATION Urinary tract infections have wide range of presentations starting from bacteriuria with minimal symptoms to florid sepsis and septic shock. A typical UTI presents with high-grade fever, suprapubic pain, renal angle tenderness and burning micturition. These symptoms are lacking in majority of patients with CAUTI. It becomes even more difficult in ICU due to ongoing concurrent antibiotics, sedatives, analgesics, and mechanical ventilation. Patients with CAUTI may present with new onset fever, altered mentation, pelvic discomfort, urinary incontinence, cloudy urine, and flank pain. Patients with spinal cord injury, in addition to these symptoms, may have autonomic dysreflexia and increased spasticity. In ICU, even in presence of indwelling catheter, fever, leukocytosis, it is difficult to make a diagnosis of CAUTI. It is basically a diagnosis of exclusion. Nevertheless, if a catheterized patient has signs and symptoms of UTI not explainable by another condition warrants treatment. And when the same organism is isolated simultaneously in urine and blood cultures, CAUTI should be thought responsible for bacteremia.14,15

DIAGNOSIS As discussed earlier, IDSA has defined ASB and CAUTI based on the colony counts. In catheterized patients, pyuria is generally not indicative of CA-bacteriuria or CAUTI. In a large study the specificity of pyuria for CA-bacteriuria in catheterized patients was 90% but sensitivity was just 47%. So just on the basis of pyuria it is difficult to differentiate between CA-bacteriuria and CAUTI. Absence of pyuria in a symptomatic patient, however, usually points toward an alternative diagnosis. Urine culture is considered the gold standard for diagnosing UTI. It can be quantified based on colony counts in patients with or without indwelling catheter (quantitative urine culture). It is imperative to collect urine sample with due precautions to make the accurate diagnosis. Ideally the urine specimen should be obtained from a freshly placed catheter, or from a voided midstream specimen in noncatheterized patients or in whom the catheter has been

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discontinued. Urine specimen should be collected directly from the catheter collection port or through needle puncture of tubing in order to maintain a closed drainage system. In a US based study the sensitivity of urine testing in combination with urine culture was detected to be 100% with a specificity of 24.1% in diagnosing CAUTI.

BLOOD CULTURES A positive blood culture along with a positive urine culture is highly suggestive of urosepsis. But it is found to be positive in only 18% of total patients. It is essential that similar organisms are grown in both urine and blood cultures. In presence of multiple organisms on urine culture, positive blood culture may help in identifying clini­ cally most important organism leading to optimization of antimicrobial therapy.16,17 Polymerase chain reaction is increasingly being utilized for early diagnosis of UTI. However, it is not readily available, is costly and may not be able to differentiate between ASB and UTI.

INFLAMMATORY MARKERS Elevated procalcitonin is predictive of bacteremia in patients with symptomatic urinary infection. It needs to be evaluated further for its utility in predicting the outcomes in UTI. Its role also needs to be better defined in the management of life-threatening urinary infection.

DIAGNOSTIC IMAGING In patients presenting with severe sepsis to ICU and suspected to have urinary cause should undergo early imaging. Imaging helps in identification of abnormalities requiring source control. It may also establish a unilateral or bilateral pathology, pyelonephritis, renal abscess, emphysematous pyelonephritis and any obstruction in the urinary tract. A contrast enhanced computed tomographic exami­ nation is considered appropriate. Magnetic resonance imaging is

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not sensitive for identifying stones or gas in tissues and thus not recommended. Renal and pelvic ultrasounds are also less sensitive, though these can be performed easily bedside.7,18-20

COMPLICATIONS Urinary tract infections account for 15% of nosocomial bacteremias. About one-fourth patients with CA-ASB develop CAUTI. Four percent patients with CA-bacteriuria develop bacteremia. CA-bacteriuria has been found to be the most common source of gram-negative bacteremia in hospitalized population. CA-bacteriuria is felt to contribute significantly to problem of antibiotic resistance in healthcare facilities. Firstly, it comprises of a large pool of antibiotic resistant organisms that can easily be transmitted to other patients who have invasive devices. Secondly, CA-bacteriuria is frequently treated inapp­ ropriately resulting in emergence of multidrug-resistant organisms. Inappropriate antimicrobial therapy also contributes toward app­ earance of nosocomial clostridium difficile colitis.21,22 Patients with prolonged ICU stay with extended indwelling catheter time are at an increased risk of developing polymicrobial bacteriuria, catheter obstruction, bacteremia, incontinence, fistula formation and local genitourinary infections. Proteus mirabilis is most commonly isolated organism during prolonged catheterization. It hydrolyses urea to ammonia resulting in formation of apatite and struvite crystals within the catheter lumen resulting in obstruction.

MANAGEMENT Antimicrobial therapy should be initiated as early as possible in a patient presenting with suspected urinary source of sepsis or septic shock, community or hospital acquired. In critically sick patients it may be worthwhile ensuring antimicrobial coverage for UTI, even when another potential source has been identified. It must be kept in mind that antibiotics alone may not be sufficient. It should be accompanied with source control (when indicated), correction of anatomical or functional defects and discontinuation of catheter at earliest feasible.

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URINE CULTURE AND CATHETER REPLACEMENT BEFORE TREATMENT Urine specimen for culture should be collected before the initiation of antibiotic therapy, especially if the patient is catheterized. If however the indwelling catheter duration is more than 2 weeks, and if there is a continuous need for catheterization, then the catheter should be replaced. In this situation, the urine specimen for culture should be obtained from a freshly placed catheter. And if catheter can be discontinued, voided midstream urine specimen should be sent for culture after its removal.

ANTIMICROBIAL THERAPY Once the microbiological sampling of urine and blood are done, antibiotics should be administered within the first hour, especially in septic patients. Antibiotics that have renal excretion achieve high drug levels in kidneys and urine, and therefore are considered appropriate. Antibiotics not excreted through the renal route may be able to treat bacteriuria effectively but fail to eradicate organisms from the urinary tract. There is also a possibility of relapse upon discontinuation of these antibiotics. High levels of antibiotics in urinary system may also not be achieved in presence of renal failure, urinary obstruction and unilateral nonfunctioning kidney. This may warrant a prolonged antimicrobial therapy. Appropriate empirical antibiotic therapy in right dosages is of utmost importance. Inappropriate therapy has been associated with high mortality. Decision of empirical antibiotics should be based upon the urine gram stain results, expected bacterial spectrum, institutional resistance profile, previous urine culture results, and individual patient’s requirement. Different empirical treatment regimens are shown in Box 2.23-25 Antibiotics should be appropriately targeted once the culture results are available. The optimal duration of antimicrobial therapy in CAUTI is unknown. But latest IDSA guidelines recommended duration is mentioned in Box 2.26-28

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Box 2: Empirical antimicrobial choices for catheter-associated urinary tract infection (CAUTI). • Mild-to-moderate infection ± fever -- Urinary fluoroquinolones: Levofloxacin and ciprofloxacin (PO) • Severe infection ± fever -- Ceftriaxone, cefepime, and ceftazidime -- Piperacillin-tazobactam combination -- Carbapenems: Meropenem, Imipenem-cilastatin, ertapenem, and doripenem -- Aztreonam -- Gentamicin ± ampicillin, tobramycin ± ampicillin, and amikacin ± ampicillin -- IV levofloxacin -- Fosfomycin • Pyelonephritis/urosepsis -- Piperacillin-tazobactam or carbapenems • Gram-positive cocci on Gram stain -- + vancomycin • Extended spectrum B lactamases (ESBL) strain suspected -- Carbapenems • Vancomycin-resistant enterococci (VRE) -- Linezolid • Carbapenemase-producing organisms -- Colistimethate • Previous exposure to antibiotics within 3–6 months -- Alternative class to be chosen • Duration of treatment -- 5 days if not severely ill -- 7 days if there is resolution of symptoms in sick patients -- 10–14 days if there is a delayed response -- 3 days in women more than 65 years, having no urinary symptoms, and catheter already removed

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ASYMPTOMATIC BACTERIURIA In a febrile ICU patient it is very common to overdiagnose and over­treat patients with ASB. Treatment of ASB is generally not indicated except in high-risk individuals like patients undergoing genitourinary surgery, and pregnant women. These patients are at high-risk of developing pyelonephritis or bloodstream infections. ASB persisting beyond 48 hours of removal of catheter should also be treated, as there is an increased risk of developing symptomatic UTI. Nonpregnant women, elderly patients living in community, catheterized patients, diabetics and persons with spinal cord injury should not receive treatment for ASB. In ICU, ASB has been found to be associated with increased hospital stay. There is limited data whether ASB in patients undergoing major surgical procedures should be treated or not.29,30

FUNGAL URINARY TRACT INFECTION Fungal infection, mainly Candida species, account for about 10–15% of nosocomial UTI. Their incidence in burns ICU is the highest, about three times of that observed in medical/surgical ICUs. There has been a recent emergence of Candida glabrata as the dominant yeast in urinary tract. This is secondary to rampant use of fluconazole. Nosocomial funguria is most common in presence of diabetes, previous antibiotic exposure, concomitant nonfungal infection, urinary tract abnormalities and underlying malignancy. Candiduria may either represent contamination of voided urine, colonized stents or catheters, bladder infection or true renal infection with candidemia. Asymptomatic nosocomial candiduria does not require treatment. However, possibility of disseminated candidiasis should be kept in mind in all hospitalized patients with candiduria, especially if candiduria is common in that particular facility. Candiduria warrants treatment in a symptomatic patient, and blood cultures and appropriate imaging to detect disseminated infection should accompany it. Fluconazole and amphotericin B deoxycholate are antifungals of choice. These drugs have a good renal excretion and thus appropriate drug levels are achieved locally. Echinocandins,

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lipid formulations of amphotericin B and other azoles (voriconazole, itraconazole, and posaconazole) are not excreted in urine, and therefore not recommended. There have been some case reports regarding effectiveness of caspofungin and micafungin in C. glabrata related UTI. Relapse rates remain high in candiduria despite apparently successful systemic or local antifungal therapy. 5-fluorocytosine may be used for some strains but requires close hematological monitoring. There is no consensus regarding the exact duration of treatment for candiduria.31,32

PREVENTION Several guidelines are available for prevention of CAUTIs. Most important determinants are judicious catheterization and strict adherence to hand hygiene practices. Use of multidimensional infection control programs for prevention of CAUTI has shown impressive results. Preventive strategies have been summarized in Box 3.33-35 The single most important preventive factor is rationale use of indwelling catheters. Catheterization should be performed for following indications: • Urinary incontinence in presence of open perineal or sacral wounds • Acute anatomic or functional urinary obstruction or retention • Perioperative use in selective surgical procedures • Improving comfort for terminally sick or end of life care patients • If accurate monitoring of urine output is required • Pressure ulcer healing for incontinent patients • Patient preference. Recently various bundles of interventions have been proposed for prevention of healthcare associated infections. Many researchers have also exhibited their successful implementation and out­ comes. This aspect seems to have a huge potential that needs to be explored.

SUMMARY Urinary tract infections are one of the major cause of nosocomial infections in critical care units. CAUTI is costly, and associated

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Update on Urinary Tract Infections Box 3: Preventive strategies for catheter-associated urinary tract infection (CAUTI). • Preventive strategies that should be routine -- Robust institutional infection control programs -- Surveillance programs in high-risk groups or units -- Rationale catheterization -- Early removal of catheter -- Aseptic technique during insertion of catheter -- Intermittent or condom catheterization where appropriate -- Use of closed drainage systems -- Placement of collection system below the level of bladder at all times -- Aseptic technique for cleaning the urethral meatus -- Avoidance of disconnection of catheter and drainage tubes -- Maintain unobstructed urine flow -- Adherence to hand hygiene practices -- Education of health care personnel about techniques of CAUTI prevention • Preventive strategies with possible benefit -- Use of antimicrobial coated catheters in patients requiring shortterm catheterization -- Suprapubic catheterization for short-term catheterization -- Use of methenamine salts in patients requiring catheterization for more than 7 days after gynecologic surgery • Preventive strategies not routinely recommended -- Use of prophylactic antimicrobials -- Use of complex closed drainage systems -- Use of hydrophilic catheters -- Use of cranberry products -- Catheter irrigation with antimicrobials or normal saline -- Routine addition of antimicrobials or antiseptics to the drainage bag -- Screening for catheter-associated asymptomatic bacteriuria (CA-ASB) -- Daily meatal cleaning with povidone-iodine solution, polyantibiotic ointment or cream, soap and water in catheterized patients -- Routine catheter change -- Prophylactic antibiotic therapy on catheter replacement or removal

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with significant patient morbidity. Wise use of catheterization has an immense capacity to reduce the incidence of CAUTI. Timely removal of catheter is another strategy to this effect. Diagnosing CAUTI in ICU is not straightforward. It is essential to differentiate between ASB and true infection. Appropriate antibiotics should be initiated at the earliest once there is a clinical suspicion. Antimicrobial resistance is increasingly becoming common in CAUTI. It is thus essential to keep local susceptibility patterns in mind while deciding the empirical regimen. Prevention of CAUTI is an important patient safety goal.

REFERENCES 1. Cohen J, Cristofaro P, Carlet J, et al. New method of classifying infection in critically ill patients. Crit Care Med. 2004;32:1510-26. 2. Saint S, Savel RH, Matthay MA. Enhancing the safety of critically ill patients by reducing urinary and central venous catheter-related infection. Am J Respir Crit Care Med. 2002;165:1475-79. 3. Haley RW, Hooten TM, Culuer DH, et al. Nosocomial infections in U.S. hospitals, 1975-1976: estimated frequency by selected characteristics of patients. Am J Med. 1981;70:947-59. 4. Nicolle LE. Urinary tract infection. Crit Care Clin. 2013;29:699-715. 5. Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:625-63. 6. Parida S, Mishra SK. Urinary tract infections in the critical care unit: A brief review. Indian J Crit Care Med. 2013;17:370-4. 7. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36:309-32. 8. Laupland KB, Zygun DA, Davies HD, et al. Incidence and risk factors for acquiring nosocomial urinary tract infection in the critically ill. J Crit Care. 2002;17:50-7. 9. Tambyah PA, Halvorson KT, Maki DG. A prospective study of the pathogenesis of catheter-associated urinary tract infections. Mayo Clin Proc. 1999;74:131-6. 10. Saint S, Chenowith CE. Biofilm and catheter-associated urinary tract infections. Infect Dis Clin North Am. 2003;17:411-32. 11. Bagshaw SM, Laupland KB. Epidemiology of intensive care unit-acquired infections. Curr Opin Infect Dis. 2006;19:67-71.

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Update on Urinary Tract Infections 12. Chang R, Greene MT, Chenoweth CE, et al. Epidemiology of hospital-acquired urinary tract-related bloodstream infection at a university hospital. Infect Control Hosp Epidemiol. 2011;32:1127-9. 13. Tambyah PA, Maki DG. Catheter-associated urinary tract infection is rarely symptomatic: a prospective study of 1,497 catheterized patients. Ann Intern Med. 2000;160:678-82. 14. Nicolle LE. Urinary catheter-associated infections. Infect Dis Clin North Am. 2012;26:13-27. 15. Warren JW, Damron D, Tenney JH, et al. Fever, bacteremia, and death as complications of bacteriuria in women with long-term urethral catheters. J Infect Dis. 1987:155;1151-8. 16. Calendra T, Cohen J, International Sepsis Forum Definition of Infection in the ICU Consensus Conference. The international sepsis forum consensus conference on definition in the intensive care unit. Crit Care Med. 2005;33:1538-48. 17. McMurray BR, Wrenn KD, Wright SW. Usefulness of blood cultures in pyelonephritis. Am J Emerg Med. 1997;15:137-40. 18. van Nieuwkoop C, Bonten TN, van’t Wout JW, et al. Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observational study. Crit Care. 2010;14:R206. 19. O’Donoghue PM, McSweeney SE, Jhaveri K. Genitourinary imaging: current and emerging applications. J Postgrad Med. 2010;56:131-9. 20. Lehmann LE, Hauser S, Malinka T, et al. Real-time polymerase chain-reaction detection of pathogens is feasible to supplement the diagnostic sequence for urinary tract infections. BJU Int. 2010;106:114-20. 21. Dallen DM, Zvonar RK, Jessamine PG, et al. An evaluation of the management of asymptomatic catheter-associated bacteriuria and candiduria at The Ottawa Hospital. Can J Infect Dis Med Microbial. 2005;16:166-70. 22. Krieger JN, Kaiser DL, Wenzel RP. Urinary tract etiology of bloodstream infections in hospitalized patients. J Infect Dis. 1983;148:57-62. 23. Kumar A, Zarychanski R, Light B, et al. Early combination antibiotics therapy yields improved survival compared with monotherapy in septic shock: a propensity matched analysis. Crit Care Med. 2010;38:1773-85. 24. Stamm WE, Hooton TM. Management of urinary tract infections in adults. N Engl J Med. 1993;329:1328-34. 25. Nicolle LE. Catheter-related urinary tract infection. Drugs Aging. 2005; 22:627-39. 26. Hooton TM. Clinical practice. Uncomplicated urinary tract infection. N Engl J Med. 2012;366:1028-37. 27. Dow G, Rao P, Harding G, et al. A prospective, randomized trial of 3 or 14 days of ciprofloxacin treatment for acute urinary tract infection in patients with spinal cord injury. Clin Infect Dis. 2004;39:658-64.

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28. Wagenlehner FM, Weidner W, Naber KG. Pharmacokinetics characteristics of antimicrobials and optimal treatment of urosepsis. Clin Pharmacokinet. 2007;46:291-305. 29. Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40:643-54. 30. Cope M, Cevallos M, Cadle RM, et al. Inappropriate treatment of catheter-associated asymptomatic bacteriuria in a tertiary care hospital. Clin Infect Dis. 2009;48:1182-8. 31. Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society Of America. Clin Infect Dis. 2009;48:503-35. 32. Sobel JD, Fisher JE, Kauffman CA, et al. Candida urinary tract infections—Epidemiology. Clin Infect Dis. 2011;52:S433-6. 33. Tambyah PA, Oon J. Catheter-associated urinary tract infection. Curr Opin Infect Dis. 2012;25:365-70. 34. Chenoweth C, Saint S. Preventing catheter-associated urinary tract infections in the intensive care unit. Crit Care Clin. 2013;29:19-32. 35. Gould CV, Umscheid CA, Agarwal RK, et al. Guideline for prevention of catheter-associated urinary tract infections 2009. Infect Control Hosp Epidemiol. 2010;31:319-26.

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5

Recurrent Urinary Tract Infection in Elderly Female Anup Kumar, Niraj Kumar

INTRODUCTION Urinary tract infection (UTI) is the most common bacterial infection in elderly women. A recurrent UTI is the infection that occurs after documented, successful resolution of an antecedent infection. It is defined as more than or equal to 3 UTIs in 12 months, or more than or equal to 2 infections in 6 months. It can be of two different types: 1. Reinfection: Reintroduction of bacteria into the urinary tract from outside. 2. Bacterial persistence: A recurrent UTI by the same bacteria re-emerging from a focus within the urinary tract, such as an infectious stone or the prostate. Incidence of bacteriuria, presence of bacteria in urine is between 15 and 20% in 65–70-year-old women and 20–50% in women more than 80 years old.1,2

RISK FACTORS It includes functional bladder abnormalities including incontinence, incomplete bladder emptying with postvoid residual urinary volume exceeding 150 mL, structural abnormalities (e.g. cystocele), type 1 or type 2 diabetes mellitus, a history of UTI (risk of UTI proportional to the number of previous UTIs and inversely proportional to the duration between the two UTIs), sexual intercourse, urinary catheterization, history of urogenital surgery among others. Activities that increase intra-abdominal pressure may aggravate incontinence, cystocele, or postvoid residual urine, and may predispose women who engage in these activities to UTIs.1,3-6 Here­ditary factors, though nonmodifiable, may have a role in recurrent UTI.4

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The lack of estrogen and resultant lower urogenital mucosal atrophy alters the vaginal, periurethral, and lower urethral environ­ ments. Estrogen plays a critical role in modulating the mucosal barrier to infection in the lower urogenital tract, including promoting healthy microbial colonies, consisting predominantly of lactoba­cilli that help to maintain a low pH environment. After menopause, the microbial colonies change and lactobacilli get replaced by Enter­obacteriaceae, such as uropathogenic Escherichia coli, which cause about 85% of UTIs.7,8 Though E. coli remains the most common uropathogen, responsible for 75% of these infections, a significant number of cases are caused by Proteus, Klebsiella, Enterobacter, Serratia, and Pseudomonas species, as well as enterococci in elderly patients (Boxes 1 and 2).2

DIAGNOSIS It can be difficult to diagnose an UTI in elderly patients as its symp­ toms may be absent or concomitant disease may mask the symptoms. So, high index of suspicion is warranted and diagnosis usually

Box 1: Risk factors for recurrent urinary tract infection (UTI) in elderly. • Functional bladder abnormalities: -- Urinary incontinence -- Incomplete bladder emptying with postvoid residual urinary volume exceeding 150 mL • Structural abnormalities (e.g. cystocele) • Infection stones • Foreign bodies • Type 1 or type 2 diabetes mellitus • A history of UTI • Sexual intercourse • Urinary catheterization • History of urogenital surgery among others • Hereditary factors • Lack of estrogen

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Update on Urinary Tract Infections Box 2: Common species of pathogen in urinary tract infection (UTI) • Escherichia coli • Proteus • Klebsiella • Enterobacter • Serratia • Pseudomonas • Enterococci

requires urinalysis and culture. The presence of pyuria alone does not warrant antimicrobial treatment as it was reported that pyuria of 10 WBCs/mm3 in midstream urine sample might not have asso­­ ciated bacteriuria in about 60% of elderly females. However, absence of pyuria is good predictor of the absence of bacteriuria.2,9 The count of more than 105 CFUs/mL of urine remains the standard diagnosis cut-off, the bacterial count of 102 CFUs/mL or more is clinically significant in catheterized patients.10 Since functional and structural abnormalities of lower genito­ u­rinary tract are responsible for recurrent UTI in elderly females, thorough evaluation of lower genitourinary tract is warranted. It includes physical examination of genitourinary tract for uterine and/ or vault prolapse, cystocele, stress urinary incontinence, urinary and fecal soiling of perineum among others. Also, investigations including serum creatinine, blood sugar, ultrasonography of kidneys, ureters, and urinary bladder (KUB) region and pelvis, excretory urography, urodynamic study, CT urography and cystoscopy are required in different combination and sequence to assess the causative functional and structural abnormalities of lower genitourinary tract.2,11

TREATMENT For acute uncomplicated symptomatic UTI, antimicrobial therapy remains the same as younger women. A 5 days’ course of nitrofurantoin 100 mg twice daily or single dose of fosfomycin 3 g or 3 days’ course of trimethoprim-sulfamethoxazole 160–800 mg twice

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daily, or 5 days’ course of trimethoprim 200 mg is usually sufficient. Fluoroquinolones should be reserved for cases other than acute uncomplicated UTI. No antibiotic treatment is required for asymptomatic bacteriuria in elderly female except for the patients with risk factors for severe diseases, e.g. indwelling catheter, institutionalized, diabetes, etc.1-3

PREVENTION OF RECURRENT URINARY TRACT INFECTION It • • •

includes the following: Counseling and behavioral modifications Nonantimicrobial measures Antimicrobial prophylaxis.

Counseling and Behavioral Modifications Patients need to be counseled about the behavioral risk factors, inc­luding low fluid intake, habitual and post-coitial delayed urination, wiping and/or washing from back to front after defecation, douching and wearing occlusive underwear, that need to be corrected. However, these factors’ association with recurrent UTI is not proven.11

Nonantimicrobial Measures Vaginal Estrogen Vaginal estrogen replacement and not oral estrogen showed imp­ rovement in local vaginal microenvironment and a trend towards preventing UTI recurrences. In addition, oral estrogen is associated with risk of coronary heart disease, venous thromboembolism, stroke, and breast cancer.11,12 In a placebo-controlled study, where intravaginal estrogens were used in postmenopausal women with recurrent UTIs with no intravaginal lactobacilli at baseline. After 1 month of treatment, 61% women in the intravaginal estrogen group had lactobacilli in vagina compared with 0% in the placebo group. The vaginal pH decreased from 5.5 to 3.8 (p