Abstract

The worldwide dissemination of carbapenemase-producing Enterobacteriaceae (CPE) has become a major therapeutic concern in clinical settings. Enterobacter cloacae is a major pathogen that causes serious hospital-acquired infections. We investigated the clinical characteristics and molecular mechanisms of the first IMP-4-producing E. cloacae clinical isolates in Korea. Five carbapenemase-producing E. cloacae strains out of 792 E. cloacae clinical isolates, which have been identified at a university hospital in Korea between March 2014 and February 2016, were included in this study. Antimicrobial susceptibilities to imipenem, meropenem, and ertapenem were tested using E-test. Carbapenemase determinant screening, genetic environment, and multilocus sequence typing were conducted using PCR and sequencing analysis. All isolates were not susceptible to at least one of the tested carbapenems and presented highly similar pulsed-field gel electrophoresis (PFGE) patterns, evidencing hospital-wide clonal dissemination. Among all isolates harboring the blaIMP-4 carbapenemase gene, four isolates identified as predominant ST74, also contained blaCMY−2. One strain, designated as rare ST194, carried blaCMY-1. The E. cloacae strain, harboring both blaIMP-4 and blaCMY-1, was resistant to all three tested carbapenems. The blaIMP-4 gene was located on a highly mobile class 1 integron, showing a new form of the blaIMP-4-qacG-aacA4 array. This is the first description of IMP-4-producing E. cloacae strains in Korea. This observation implicates the widespread of blaIMP-4 in Enterobacteriaceae clinical isolates and provides insights into the epidemic potential and clinical therapeutic importance of IMP-4-producing E. cloacae for healthcare-associated infections.

Highlights

  • The spread of carbapenemase-producing Enterobacteriaceae (CPE) has become a prominent health-care challenge worldwide in the treatment of infectious diseases

  • The carbapenemaseproducing E. cloacae strains were isolated from various departments and two of them were recovered from the open wounds in diabetic feet

  • The antimicrobial susceptibility profiles of five E. cloacae isolates with blaIMP-4 are presented in Supplementary Table 1

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Summary

Introduction

The spread of carbapenemase-producing Enterobacteriaceae (CPE) has become a prominent health-care challenge worldwide in the treatment of infectious diseases. IMP-type CPEs have been reported globally (Queenan and Bush, 2007; Tzouvelekis et al, 2012) and have become the IMP-4-Producing E. cloacae in Korea predominant form in Australia (Espedido et al, 2008; Leung et al, 2013; Sidjabat et al, 2015) since the first report of IMP-1 from Pseudomonas aeruginosa in Japan (Watanabe et al, 1991). IMP-4producing E. cloacae was reported in Australia and caused clinical outbreaks, which brought greater challenges to infection control (Leung et al, 2013; Chapuis et al, 2016; Pang et al, 2016). The highly mobile class 1 integron facilitates global spread of the blaIMP-4 gene (Espedido et al, 2008; Partridge et al, 2012)

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