Molecular and epidemiological characterization of IMP-type metallo-β-lactamase-producing Enterobacter cloacae in a Large tertiary care hospital in Japan

Abstract

IMP-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-producing Enterobacter cloacae (IMP-producing E. cloacae) have not been systematically evaluated. We conducted a retrospective, matched case-control study of patients from whom IMP-producing E. cloacae isolates were obtained, in addition to performing thorough molecular analyses of the clinically obtained IMP-producing E. cloacae isolates. Unique cases with IMP-producing E. cloacae isolation were included. Patients with IMP-producing E. cloacae were matched to uninfected controls at a ratio of 1 to 3. Fifteen IMP-producing E. cloacae cases 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-producing E. cloacae isolates were obtained had indwelling devices at the time of isolation, compared with one (2.2%) uninfected control. Independent predictors for isolation of IMP-producing E. cloacae were 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-producing E. cloacae-caused bacteremia was significantly higher (40%) than the rate in controls. IMP-producing E. cloacae isolates 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-producing E. cloacae isolates had a MIC of ≤ 1 μg/ml. A phylogenetic tree showed a close relationship among the IMP-producing E. cloacae samples. Indwelling devices, exposure to cephalosporin, and a history of invasive procedures were associated with isolation of IMP-producing E. cloacae. Screening for carbapenemase production is important in order to apply appropriate clinical management and infection control measures.

FIG 1

Phylogenetic tree of IMP-metallo-β-lactamase-producing Enterobacter cloacae isolates. The group of isolates included EC4, EC5, EC7, EC10, EC12, EC13, EC14, EC16, EC17, EC18, EC19, EC20, EC21, EC22, EC23, EC24, and the reference. Outliers included EC2, EC3, EC8, EC9, and EC15. EC2 and EC3 were E. cloacae isolates from NCGM in 2007. EC8 and EC9 were IMP-producing E. cloacae isolates from other facilities in Japan. EC15 was obtained from a patient who had been transferred from another hospital. EC10 (blood) and EC12 (wound) were IMP-producing E. cloacae isolates from the same patient (patient 4). EC15 (blood) and EC23 (urine) were IMP-producing E. cloacae isolates from the same patient (patient 15). Reference, de novo assembled contigs of all E. cloacae isolates used in this study were used as the reference.