Community-onset carbapenem-resistant Klebsiella pneumoniae urinary tract infections in infancy following NICU hospitalisation

doi:10.1016/j.jpurol.2017.02.008

Journal of Pediatric Urology

Volume 13, Issue 5, October 2017, Pages 495.e1-495.e6

https://doi.org/10.1016/j.jpurol.2017.02.008 Get rights and content

Summary

Introduction

Urinary tract infection (UTI) is a common bacterial infection in childhood with favourable outcome. However, the recent emergence of UTI caused by multidrug-resistant pathogens, such as carbapenem-resistant Enterobacteriaceae (CRE), has become a great concern worldwide. CRE are mainly responsible for nosocomial infections and community-onset CRE infections in healthy individuals are rare.

Objectives

In this study, we report a series of infants without substantial genitourinary abnormalities that were admitted with community-onset urinary tract infections (UTIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) and we discuss their aetiology.

Methods

We retrospectively reviewed the medical records of nine infants who presented from community to the paediatric ward with CRKP urinary tract infections, as well as all affected neonates of a concomitant CRKP outbreak that occurred in the neonatal intensive care unit (NICU) in a tertiary hospital (period from April 2009 to July 2012). We further retrieved all culture-proven CRKP infections of any site from 2007 to 2015 in our paediatric department.

Results

Over a 33-month period, nine infants, all males, aged 0.9–19.3 (median 4.0) months, were admitted to the Department of Paediatrics with UTI caused by CRKP. Three of them were diagnosed with urinary tract abnormalities but only one had vesicoureteral reflux (VUR), which was a UTI-associated one. History revealed that they had all been hospitalised in the same NICU during a concurrent long-lasting CRKP outbreak for a median of 17 (2–275) days and thereafter presented with CRKP UTI 15 to 207 (median 41) days after NICU discharge. The antibiotic susceptibility and phenotypic characteristics were identical among all isolates in NICU and the paediatric ward. The summary Figure shows a timeline of NICU hospitalisation indicative of its duration and subsequent CRKP UTI of study participants is presented.

Conclusions

These cases illustrate that UTI caused by multidrug-resistant pathogens does not necessarily imply an underlying urinary track anomaly. Hospital acquisition of CRKP may well provoke community-onset multidrug-resistant UTI in infants months later, and this highlights the value of detailed history in patients with unusual pathogens. Cautious use of broad-spectrum antibiotics in NICUs and infection control measures would minimise the spread of multidrug-resistant pathogens in infants in the community.

Introduction

Urinary tract infection (UTI) is a common bacterial infection in childhood and a common reason for hospitalisation [1]. The prognosis is usually favourable, but relies on timely administration of appropriate empirical antibiotics. Escherichia coli is the most frequent causative agent, followed by Klebsiella spp, Proteus spp, and other Enterobacteriaceae [2], [3].

The empirical treatment of community-onset UTI is based on the expected sensitivity profile of the most common UTI pathogens [3]. UTI caused by Enterobacteriaceae producing extended spectrum beta-lactamases (ESBL) has been substantially increased over the last decade, not just in hospital settings but also in the community [2], [4], [5]. Their emergence has mainly been attributed to underlying genitourinary anomalies, presence of urinary catheters, or previous hospitalisation and antibiotic use [4], [5]. Carbapenems have been the most effective agents against these organisms; however, the recent rise of carbapenem-resistant Enterobacteriaceae (CRE) has resulted in treatment failures [4], [6], [7], [8]. CRE colonise patients' gastrointestinal tracts and spread rapidly in healthcare settings by horizontal dissemination of antibiotic resistance genes [9]. Contrary to the well-established community dissemination of ESBL-producing Enterobacteriaceae, community-onset CRE UTI remains extremely rare in children.

We report a cluster of community-onset UTI caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) in infants without substantial genitourinary abnormalities and its association with a neonatal intensive care unit (NICU) CRKP outbreak.

Section snippets

Study period, study participants, and definitions

From October 2009 to July 2012, an unusually high frequency of community-onset UTI caused by CRKP in infants was observed in the Paediatric Department of Heraklion University Hospital (HUH), Greece, which is the referral one for the island of Crete. Based on this observation, we reviewed the medical records of all patients that presented from the community with CRKP UTI during this period, aiming to identify the potential source of this unusual pathogen. Clinical and epidemiological parameters

Community-onset CRKP UTIs in infancy

From October 2009 to July 2012, nine febrile infants were admitted with no apparent focus of fever. Patient characteristics are depicted in Table 1. The infants were all uncircumcised males and the median age at presentation was 4.0 months (range 0.9–19.3 months) (Table 1). Urine and blood cultures were received from all, together with cerebrospinal fluid cultures from those younger than 3 months and empirical antibiotic treatment was started with a third generation cephalosporin. K. pneumoniae

Discussion

In this study, we report nine infants presenting with community-onset UTI caused by CRKP. The infants were all uncircumcised males and although three of them had urinary tract abnormalities, only one had VUR. All shared a history of hospitalisation in the same NICU during a CRKP outbreak. Most of them presented with CRKP UTI within 6 months after NICU discharge. Our evidence points to CRKP acquisition during NICU hospitalisation.

CRKP was first detected in 1996 in the USA and it was spread

Conflict of interest

None.

Funding

None.

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Klebsiella pneumoniae is the most common pathogen causing neonatal infections, leading to high mortality worldwide. Along with increasing antimicrobial use in neonates, carbapenem-resistant K. pneumoniae (CRKP) has emerged as a severe challenge for infection control and treatment. However, no comprehensive systematic review is available to describe the global epidemiology of neonatal CRKP infections. We therefore performed a systematic review of available data worldwide and combined a genome-based analysis to address the prevalence, clonal diversity, and carbapenem resistance genes of CRKP causing neonatal infections.
We performed a systematic review of studies reporting population-based neonatal infections caused by CRKP in combination with a genome-based analysis of all publicly available CRKP genomes with neonatal origins. We searched multiple databases (PubMed, Web of Science, Embase, Ovid MEDLINE, Cochrane, bioRxiv, and medRxiv) to identify studies that have reported data of neonatal CRKP infections up to June 30, 2022. We included studies addressing the prevalence of CRKP infections and colonization in neonates but excluded studies lacking the numbers of neonates, the geographical location, or independent data on Klebsiella or CRKP isolates. We used narrative synthesis for pooling data with JMP statistical software. We identified 8,558 articles and excluding those that did not meet inclusion criteria. We included 128 studies, none of which were preprints, comprising 127,583 neonates in 30 countries including 21 low- and middle-income countries (LMICs) for analysis. We found that bloodstream infection is the most common infection type in reported data. We estimated that the pooled global prevalence of CRKP infections in hospitalized neonates was 0.3% (95% confidence interval [CI], 0.2% to 0.3%). Based on 21 studies reporting patient outcomes, we found that the pooled mortality of neonatal CRKP infections was 22.9% (95% CI, 13.0% to 32.9%). A total of 535 neonatal CRKP genomes were identified from GenBank including Sequence Read Archive, of which 204 were not linked to any publications. We incorporated the 204 genomes with a literature review for understanding the species distribution, clonal diversity, and carbapenemase types. We identified 146 sequence types (STs) for neonatal CRKP strains and found that ST17, ST11, and ST15 were the 3 most common lineages. In particular, ST17 CRKP has been seen in neonates in 8 countries across 4 continents. The vast majority (75.3%) of the 1,592 neonatal CRKP strains available for analyzing carbapenemase have genes encoding metallo-β-lactamases and NDM (New Delhi metallo-β-lactamase) appeared to be the most common carbapenemase (64.3%). The main limitation of this study is the absence or scarcity of data from North America, South America, and Oceania.
CRKP contributes to a considerable number of neonatal infections and leads to significant neonatal mortality. Neonatal CRKP strains are highly diverse, while ST17 is globally prevalent and merits early detection for treatment and prevention. The dominance of bla_NDM carbapenemase genes imposes challenges on therapeutic options in neonates and supports the continued inhibitor-related drug discovery.
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View full text

Community-onset carbapenem-resistant Klebsiella pneumoniae urinary tract infections in infancy following NICU hospitalisation

Summary

Introduction

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

Study period, study participants, and definitions

Community-onset CRKP UTIs in infancy

Discussion

Conflict of interest

Funding

Clin Microbiol Infect

J Infect

Lancet Infect Dis

J Hosp Infect

Am J Infect Control

J Hosp Infect

Pediatric urinary tract infections: diagnosis and treatment

Expert Rev Anti Infect Ther

Long-term resistance trends of uropathogens and association with antimicrobial prophylaxis

Pediatr Nephrol

Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months

Pediatrics

Non-Escherichia coli versus Escherichia coli community-acquired urinary tract infections in children hospitalized in a tertiary center: relative frequency, risk factors, antimicrobial resistance and outcome

Pediatr Infect Dis J

Risk factors in community-acquired urinary tract infections caused by ESBL-producing bacteria in children

Pediatr Nephrol

Global spread of carbapenemase-producing Enterobacteriaceae

Emerg Infect Dis

Carbapenem-resistant Enterobacteriaceae infections in children: an Italian retrospective multicenter study

Pediatr Infect Dis J

Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance

Antimicrob Agents Chemother

Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions

Clin Microbiol Rev