Abstract

On 31 May 2011, after notification of Klebsiella pneumoniae (KP)(OXA-48;CTX-M-15) in two patients, nosocomial transmission was suspected in a Dutch hospital. Hospital-wide infection control measures and an outbreak investigation were initiated. A total of 72,147 patients were categorised into groups based on risk of OXA-48 colonisation or infection, and 7,527 were screened for Enterobacteriaceae(OXA-48) by polymerase chain reaction (PCR). Stored KP isolates (n=408) were retrospectively tested for OXA-48 and CTX-M-1 group extended-spectrum beta-lactamases (ESBL). 285 KP isolates from retrospective and prospective patient screening were genotyped by amplified fragment length polymorphism (AFLP). 41 isolates harbouring different Enterobacteriaceae species were analysed by plasmid multilocus sequence typing (pMLST). No nosocomial transmission of Enterobacteriaceae(OXA-48) was detected after 18 July 2011. Enterobacteriaceae(OXA-48) were found in 118 patients (KP (n=99), Escherichia coli (n=56), ≥1 Enterobacteriaceae(OXA-48) species (n=52)), of whom 21 had clinical infections. 39/41 (95%) of OXA-48 containing plasmids were identical in pMLST. Minimum inhibitory concentrations (MICs) of KP(OXA-48) and E. coli(OXA-48) for imipenem and meropenem ranged from ≤1 to ≥16 mg/L, and 153/157 (97%) had MIC >0.25 mg/L for ertapenem. AFLP identified a cluster of 203 genetically linked isolates (62 KP(OXA-48;CTX-M15); 107 KP(CTX-M-15); 34 KP(OXA-48)). The ‘oldest’ KP(CTX-M-15) and KP(OXA-48) clonal types originated from February 2009 and September 2010, respectively. The last presumed outbreak-related KP(OXA-48) was detected in April 2012. Uncontrolled transmission of KP(CTX-M-15) evolved into a nosocomial outbreak of KP(OXA-48;CTX-M15) with large phenotypical heterogeneity. Although the outbreak was successfully controlled, the contribution of individual containment measures and of the hospital relocating into a new building just before outbreak notification was impossible to quantify.

Highlights

  • The number of infections caused by Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBL), such as for example those with CTX-M-1 group ESBL and/or carbapenemases is rapidly increasing worldwide [1,2,3]

  • After notification in May 2011 of K. pneumoniaeCTX-M-15 simultaneously positive for OXA-48, in clinical cultures of two patients who had been recently discharged from hospital A, an outbreak team was assembled on 1 June

  • Retrospective screening The identification of two patients with K. pneumoniaeCTX-M-15;OXA-48 by other laboratories in March and April 2011 alerted to the outbreak upon notification on 31 May 2011

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Summary

Introduction

The number of infections caused by Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBL), such as for example those with CTX-M-1 group ESBL and/or carbapenemases is rapidly increasing worldwide [1,2,3]. Carbapenem resistance in Enterobacteriaceae is mainly caused by production of one of three groups of carbapenemases: Ambler class A (Klebsiella pneumoniae carbapenemase (KPC)), B (metallo-beta-lactamases, e.g. Verona integron-encoded metallo-beta-lactamase (VIM), New Delhi metallo-betalactamase (NDM)), and D (oxacillinases, e.g. OXA-48), usually in combination with ESBL-production. OXA-48 oxacillinase was identified for the first time in a K. pneumoniae isolate from Istanbul, Turkey in 2001 [4], and patients infected or carrying such bacteria have been reported from Asia [5], north Africa [6,7,8], South Africa [9], Europe [10,11,12] and north America [13]. PneumoniaeCTX-M-15 isolates were identified and the occurrence of this clonal type gradually increased since, despite implementation of several control measures to interrupt transmission In February 2009 two clonal type K. pneumoniaeCTX-M-15 isolates were identified and the occurrence of this clonal type gradually increased since, despite implementation of several control measures to interrupt transmission

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