Molecular Characteristics of First IMP-4-Producing Enterobacter cloacae Sequence Type 74 and 194 in Korea

Abstract

The worldwide dissemination of carbapenemase-producing <i>Enterobacteriaceae</i> (CPE) has become a major therapeutic concern in clinical settings. <i>Enterobacter cloacae</i> is a major pathogen that causes serious hospital-acquired infections. We investigated the clinical characteristics and molecular mechanisms of the first IMP-4-producing <i>E. cloacae</i> clinical isolates in Korea. Five carbapenemase-producing <i>E. cloacae</i> strains out of 792 <i>E. cloacae</i> 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 <i>E</i>-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 <i>bla</i>_IMP-4 carbapenemase gene, four isolates identified as predominant ST74, also contained <i>bla</i>_CMY-2. One strain, designated as rare ST194, carried <i>bla</i>_CMY-1. The <i>E. cloacae</i> strain, harboring both <i>bla</i>_IMP-4 and <i>bla</i>_CMY-1, was resistant to all three tested carbapenems. The <i>bla</i>_IMP-4 gene was located on a highly mobile class 1 integron, showing a new form of the <i>bla</i>_IMP-4-<i>qacG</i>-<i>aacA4</i> array. This is the first description of IMP-4-producing <i>E. cloacae</i> strains in Korea. This observation implicates the widespread of <i>bla</i>_IMP-4 in <i>Enterobacteriaceae</i> clinical isolates and provides insights into the epidemic potential and clinical therapeutic importance of IMP-4-producing <i>E. cloacae</i> for healthcare-associated infections.