Molecular and Epidemiological Characterization of IMP-Type Metallo-β-Lactamase-Producing Enterobacter cloacae in a Large Tertiary Care Hospital in Japan

Abstract

ABSTRACTIMP-type metallo-β-lactamase enzymes have been reported in different geographical areas and in various Gram-negative bacteria. However, the risk factors and epidemiology pertaining to IMP-type metallo-β-lactamase-producingEnterobacter cloacae(IMP-producingE. cloacae) have not been systematically evaluated. We conducted a retrospective, matched case-control study of patients from whom IMP-producingE. cloacaeisolates were obtained, in addition to performing thorough molecular analyses of the clinically obtained IMP-producingE. cloacaeisolates. Unique cases with IMP-producingE. cloacaeisolation were included. Patients with IMP-producingE. cloacaewere matched to uninfected controls at a ratio of 1 to 3. Fifteen IMP-producingE. cloacaecases were identified, with five of the isolates being obtained from blood, and they were matched to 45 uninfected controls. All (100%) patients from whom IMP-producingE. cloacaeisolates were obtained had indwelling devices at the time of isolation, compared with one (2.2%) uninfected control. Independent predictors for isolation of IMP-producingE. cloacaewere identified as cephalosporin exposure and invasive procedures within 3 months. Although in-hospital mortality rates were similar between cases and controls (14.3% versus 13.3%), the in-hospital mortality of patients with IMP-producingE. cloacae-caused bacteremia was significantly higher (40%) than the rate in controls. IMP-producingE. cloacaeisolates were frequently positive for other resistance determinants. The MICs of meropenem and imipenem were not elevated; 10 (67%) and 12 (80%) of the 15 IMP-producingE. cloacaeisolates had a MIC of ≤1 μg/ml. A phylogenetic tree showed a close relationship among the IMP-producingE. cloacaesamples. Indwelling devices, exposure to cephalosporin, and a history of invasive procedures were associated with isolation of IMP-producingE. cloacae. Screening for carbapenemase production is important in order to apply appropriate clinical management and infection control measures.