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Treatment of Urinary Tract Infections Caused by ESBL-Producing

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Treatment of Urinary Tract Infections Caused by ESBL-Producing Jayachitra PIDJ ESPID REPORTS AND REVIEWS PIDJ-219-663 CONTENTS UTI Caused by E. Coli or Klebsiella pneumoniae UTI Caused by E. coli or Klebsiella EDITORIAL BOARD Editors: Shamez N. Ladhani and Emmanuel J. Roilides Bitsori and Galanakis Board Members David Burgner (Melbourne, Cristiana Nascimento-Carvalho (Larissa, Greece) XXX Australia) (Bahia, Brazil) Tobias Tenenbaum (Mannhein, Kow-Tong Chen (Tainan,Taiwan) Ville Peltola (Turku, Finland) Germany) 11/19/2019 on BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3TDbD+Y6NAIGu+rtg6z5XDLNf0MN8NgKi8U6WmRZ598BTdqYKNjB+OQ== by https://journals.lww.com/pidj from Downloaded Luisa Galli (Florence, Italy) Ira Shah (Mumbai, India) Marc Tebruegge (Southampton, UK) Downloaded Steve Graham (Melbourne, George Syrogiannopoulos Pediatr Infect Dis J Australia) from https://journals.lww.com/pidj Lippincott Williams & Wilkins Treatment of Urinary Tract Infections Caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae Hagerstown, MD by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3TDbD+Y6NAIGu+rtg6z5XDLNf0MN8NgKi8U6WmRZ598BTdqYKNjB+OQ== Maria Bitsori, MD, PhD, and Emmanouil Galanakis, MD, PhD rinary tract infections (UTIs) are usually and classifiedβ -lactamases into 4 classes, A, 5% among community-acquired UTIs and Ucaused by Gram-negative Enterobacte- C and D serine β-lactamases and B metallo- 12% among healthcare-associated ones.5 riaceae, the most common pathogens being β-lactamases.3 A functional classification Global trends for AmpC uropathogens Escherichia coli and Klebsiella pneumo- correlated the properties of a specific enzyme are not available but surveillance programs niae.1,2 Antimicrobial resistance is increasing with the resistance profile of a clinical iso- suggest high rates in regions with high ESBL among uropathogens and the production of late and included 3 major groups, 1, 2 and 3 prevalence.4 In a multicenter study from β-lactamases is a major resistance mecha- with subgroups.3 In Table 1, we summarize China, 2% of E. coli and 10% of K. pneu- nism.3 Extended spectrum β lactamases the clinically important β-lactamases pro- moniae strains isolated from children, mostly (ESBLs) producing pathogens exhibit resist- duced by resistant E. coli and K. pneumoniae from urine, were found to bear plasmid- ance not only to newer β-lactams, including uropathogens. mediated AmpC β-lactamases.8 third generation cephalosporins and monobac- Carbapenemase-producing Entero- tams, but also to other classes of antibiotics.3,4 bacteriaceae are less common than ESBL ESBL resistance genes are located on plas- EPIDEMIOLOGY OF ESBL E. or AmpC producers but their spread is of 2019 mids which are transferrable to other strains, COLI AND K. PNEUMONIAE particular concern. Global frequencies of thus posing considerable infection control UROPATHOGENS approximately 4% for K. pneumoniae and 3,4 issues. UTIs caused by ESBL-producing E. The first transferrableβ -lactamase <1% for E. coli isolated from children have coli and K. pneumoniae are the most common was named TEM, after the name of a patient been reported.9 5 ESBL infections in childhood. Herein, we in Greece in the early 1960s with an E. Risk factors for ESBL uropathogens summarize available data on these pathogens coli–positive blood culture.4 The first ESBL include recurrent UTIs, vesicoureteral reflux, with a focus on treatment choices. enzyme of sulphydryl variable type was iden- previous exposure to antibiotics, younger age e332 tified in a Klebsiella strain isolated in Ger- and Klebsiella species.5,6 Receipt of antibiot- BETA-LACTAMASES AND ESBL many in 1983.6 Until 2000, ESBL-producing ics during the previous 1–3 months, especially CLASSIFICATION Enterobacteriaceae caused mainly nosoco- as continuous prophylaxis, has been increas- e335 Beta-lactamases are classified either mial infections. However, with the gradual ingly recognized as a major risk factor for the 10–12 by their structure or by their functional prop- predominance of cefotaximase of Munich development of resistant uropathogens. on (CTX-M) producing strains and after intro- AmpC uropathogens have been associated 11/19/2019 erties. The structural way was based on pro- 0891-3668 tein sequence and active site of the enzymes duction of E. coli ST131 (a CTX-M-15 with previous exposure specifically to third strain), they quickly spread to the commu- generation cephalosporins as well as under- 4,6,7 10,11 Accepted for publication September 4, 2019. nity. Despite the international surveillance lying conditions requiring hospitalization. 10.1097/INF.0000000000002487 From the Department of Paediatrics, Heraklion Uni- programs, data on ESBL uropathogens in Moreover, children with an index UTI by an versity Hospital, Crete, Greece. children remain limited. In a meta-analysis, ESBL or AmpC E. coli or Klebsiella patho- The authors have no funding or conflicts of interest to disclose. an ESBL prevalence of 14% was found gen are at increased risk for a subsequent The Pediatric Infectious Disease Journal Address for correspondence: Emmanouil Galanakis, among 7374 urine isolates, with E. coli and UTI by the same or different organism with MD, PhD, Department of Paediatrics, University of Klebsiella spp. being the most common.5 high resistance properties.12 Risk factors for Crete, Crete, Greece. E-mail: [email protected]. Rates were high in Africa (76%) and South- carbapenemase-producing uropathogens, in Copyright © 2019 Wolters Kluwer Health, Inc. All 38 rights reserved. East Asia (37%), intermediate in Europe particular K. pneumoniae, include prolonged ISSN: 0891-3668/19/3812-e332 (12%) and Eastern Mediterranean (5%) and hospitalization, especially in intensive-care DOI: 10.1097/INF.0000000000002487 lowest (2%) in the Americas. ESBL rate was settings, invasive medical devices and travel 12 TheThe ESPID ESPID Reports Reports and and Reviews Reviews of of Pediatric Pediatric Infectious Infectious Diseases Disease series Journal topics, series authors topics, andauthors contents and contents are chosen are andchosen approved and approvedindependently independently by the by Editorial the Editorial Board Board of ESPID. of ESPID. December e332 | www.pidj.com The Pediatric Infectious Disease Journal • Volume 38, Number 12, December 2019 2019 Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. The Pediatric Infectious Disease Journal • Volume 38, Number 12, December 2019 UTI Caused by E. coli or Klebsiella have retained their activity against ESBL E. TABLE 1. Clinically Important β-lactamases Produced by Resistant coli and K. pneumoniae and re-emerged as Escherichia coli and Klebsiella pneumoniae Uropathogens options for UTIs.3,4,16 Data for children are limited, but these agents seem worth of con- Ambler Bush-Jacoby-Medei- Mechanism of Representative Classification ros Classification Resistance enzymes sideration especially for non–life-threatening infections.3,4 The oral formulation of fosfo- Class A 2be, 2br, 2ber ESBLs TEM, SHV, CTX-M mycin is particularly appealing for treatment 2f Carbapenemases K. pneumoniae carbapen- continuation after initial improvement. Nitro- emase (KPC) Class B 3a, 3b Carbapenemases (metallo-β VIM, IMP, NDM furantoin could only be an option for cysti- lactamases) tis, given its insufficient serum levels and Class C 1 Plasmid-mediated cephalo- CMY, FOX, ACT minimal parenchymal penetration.16 There sporinases (AmpC) are efficacy data for extended spectrum peni- Class D 2df Penicillinases and carbapen- OXA cillin derivatives, such as pivmecillinam or emases temocillin in uncomplicated UTIs in chil- dren, but these agents are not widely avail- to endemic areas.4,6,9 Neonates seem to be a ANTIMICROBIAL AGENTS FOR able.3,4 Carbapenemase-producing pathogens particularly high risk population and these ESBL E. COLI AND K. PNEUMONIAE have drawn attention to colistin.9 Colistin strains often cause outbreaks in neonatal UTIS is well tolerated in children and remains a wards, resulting in high rates of morbidity The usual first-line therapeutic second line option, but is associated with and mortality, and in colonization and UTIs choices, that is, penicillins and cephalospor- nephrotoxicity and is prone to emergence of by unusual pathogens months later.13 Rates of resistance, making the addition of another ins are in vitro ineffective against ESBL- 9 ESBL/AmpC-carriers healthy toddlers have producing E. coli and K. pneumoniae strains, antibiotic necessary. been reported to range from 4% to 6.5% in and coresistance to other agents narrows 4,6 Carbapenems Europe to 23% in Asia. Apart from health- further the therapeutic armamentarium. Car- care-associated factors, an important role of bapenems are the most reliable, and in severe Carbapenems with their excellent in vitro activity are reserved for children with widespread broad spectrum antibiotics in cases, the only, treatment option; however, 4,6 severe clinical presentation or nosocomial farming practices has been suggested. their judicious use is needed to avoid devel- infection. Most of the experience in pedi- opment of carbapenemase-producing patho- atrics is with imipenem or meropenem,9,16 gens. Given the limited development of novel LABORATORY IDENTIFICATION OF but recent reports have highlighted the use agents for resistant Gram-negative patho- ESBL E. COLI AND K. PNEUMONIAE of ertapenem particularly in UTIs.4 Car- gens, alternatives have been sought among Every Enterobacteriaceae uropathogen bapenemase production does not necessar-
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