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

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 bla_IMP-4 carbapenemase gene, four isolates identified as predominant ST74, also contained bla_CMY-2. One strain, designated as rare ST194, carried bla_CMY-1. The E. cloacae strain, harboring both bla_IMP-4 and bla_CMY-1, was resistant to all three tested carbapenems. The bla_IMP-4 gene was located on a highly mobile class 1 integron, showing a new form of the bla_IMP-4-qacG-aacA4 array. This is the first description of IMP-4-producing E. cloacae strains in Korea. This observation implicates the widespread of bla_IMP-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.