Molecular characterization and risk factors for carbapenem-resistant Gram-negative bacilli colonization in children: emergence of NDM-producing Acinetobacter baumannii in a newborn intensive care unit in Turkey

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Summary

Background

Multidrug-resistant Gram-negative bacilli are responsible for more than 50% of healthcare-associated infections. Colonization dynamics, characteristics, and risk factor data for CR-GNB are scarce in children.

Aim

To examine the molecular characteristics of, and risk factors for nosocomial colonization with, carbapenem-resistant Gram-negative bacilli (CR-GNB) in hospitalized paediatric patients in a tertiary university hospital's paediatric units in Turkey.

Methods

A prospective case–control study was performed at a university hospital in Istanbul, Turkey.

Findings

A total of 1840 rectal swab specimens were collected from all 762 hospitalized children between March 2013 and October 2013. Among them, 176 (23%) patients were colonized with CR-GNB. Of these, 72 (9%) patients were colonized with carbapenem-resistant Enterobacteriaceae, 138 (18%) with CR-non-fermenter Gram-negative bacilli (CR-NF) and 34 (4%) with both. The median CR-GNB colonization time was 10 days (range: 1–116). The median duration of rectal colonization with CR-GNB was 8 days (range: 1–160). NDM (31%) was the second most frequent carbapenemase identified in Acinetobacter baumannii isolates, and has not previously been detected in Turkey. All of the 17 patients colonized with NDM-producing A. baumannii were newborns in the neonatal intensive care unit. Independent risk factors for CR-GNB colonization were: age <1 year, nasogastric tube placement, presence of underlying chronic diseases, ampicillin usage, surgical intervention, and carbapenem use.

Conclusion

This is the first description of NDM in A. baumannii in newborn units in Turkey. Carbapenem usage is a common independent risk factor for both CRE and CR-NF colonization, which underscores the importance of antibiotic stewardship programmes.

Introduction

Multidrug-resistant Gram-negative bacilli (MDR-GNB), including the extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae family (Klebsiella pneumoniae, Escherichia coli and Enterobacter spp.), multidrug-resistant Pseudomonas aeruginosa and Acinetobacter spp., are the leading causative pathogenic micro-organisms responsible for more than 50% of healthcare-associated infections.1, 2 MDR-GNB infections are associated with longer hospital stay, higher hospitalization cost and mortality rates ranging from 30% to 70%.3, 4

It has been well documented that the major cause of the emergence of MDR pathogens is the imprudent use of antibiotics.2 Carbapenems are one of the most widely used antibiotics in the treatment of infections caused by ESBL- and Amp-C β-lactamase-producing micro-organisms. This has led to an increase in their usage. Thus, selective use of these agents has led to the development of resistance since the 1990s. Carbapenem-resistant Gram-negative bacilli (CR-GNB) may occur by various mechanisms, including the following: (i) reduced outer membrane permeability resulting from porin loss (such as OprD porin loss in P. aeruginosa) and activation of multidrug efflux pumps in response to antibiotic exposure; (ii) in combination with the production of an ESBL or of AmpC-type β-lactamase; (iii) production of carbapenem-hydrolysing enzymes (carbapenemases).5, 6 Carbapenemases have been classified as members of the Ambler molecular system, and include Class A, the serine-based penicillinases (e.g. KPC, GES, and SME types), Class B enzymes, which require the presence of zinc for activity and, hence, are referred to as metallo-β-lactamases (e.g. IMP, VIM, and NDM types), and Class D, the serine-based oxacillinases (e.g. OXA-23, -24, -48, and -58).7 Moreover, CR-GNB may have resistance to other classes of antibiotics, including aminoglycosides, fluoroquinolones, and cotrimoxazole, resulting in limited therapy options.8 For this reason, the crude mortality rate in CR-GNB bacteria is very high. Considering the high mortality rates, a description of the risk factors for developing CR-GNB infections in patients initially colonized with CR-GNB is important for controlling these infections in hospitals.9 Colonization dynamics, characteristics, and risk factors for CR-GNB are well established in adults, but data in children are scarce.

Therefore, we evaluated the risk factors for CR-GNB colonization and determined the resistance genes involved in children in a tertiary university hospital.

Section snippets

Institution and study population

The study was performed in a tertiary university hospital of Marmara University Pendik Research and Training Hospital in Istanbul, Turkey. The hospital has a 649-bed capacity, including all major paediatric and paediatric surgery departments and services, plus neonatal, paediatric, and paediatric surgery intensive care units (ICUs). After the first case of carbapenem-resistant Acinetobacter baumannii bloodstream infection, susceptible only to colomycin and tigecycline, was reported in March

Results

Between March 2013 and October 2013, a total of 762 children were followed up weekly for rectal colonization with CR-GNB. Of these, 176 (23%) were found to be colonized with any CR-GNB, including K. pneumoniae (N = 54, 13.6%), Pseudomonas spp. (N = 71, 17.8%) (P. aeruginosa, N = 65; Pseudomonas putida, N = 5; Pseudomonas florescens, N = 1), A. baumannii (N = 55, 13.8%), Stenotrophomonas maltophilia (N = 30, 7.5%), E. coli (N = 11, 2.8%) and Enterobacter spp. (N = 10, 2.5%). In total, 176

Discussion

In this study, we determined the presence of resistance genes by PCR in CR-GNB-colonized hospitalized children in a prospective surveillance study.

To the best of our knowledge, ours is the first report of the presence of NDM carbapenemases in A. baumannii isolates from Turkey. In our study, OXA-23 was the most frequent carbapenemase identified among the carbapenem-resistant A. baumannii isolates, which is similar to other reports. NDM was the second most frequent carbapenemase identified. In

Conflict of interest statement

None declared.

Funding source

This study is financially supported by Turkish Academy of Sciences.

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