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

Abstract

d IMP-type metallo-␤-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-␤-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 g/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.

Emerging Carbapenem-Resistant &lt;i&gt;Enterobacter cloacae&lt;/i&gt; Producing OXA-48-, VIM- and IMP-Type-&lt;i&gt;β&lt;/i&gt;-Lactamases in Eastern Cape Hospitals in South Africa

“…Susceptibility to antimicrobial agents is presented in Table 1.The minimal inhibitory concentration (MIC) breakpoints for imipenem and meropenem were not elevated and was in the susceptible range < 1 for these isolates. Similar findings were observed in the study by Hayakawa et al, in 2014 underscoring the difficulties in identifying metallo-β-carbapenemase-producing organisms primarily based on MIC results [8]. This could also be used as a possible explanation for the one bla VIM -positive isolate that was fully susceptible to the carbapenem group of antibiotics in our study.…”

“…IMP-type-producing E. cloacae have been documented globally, for example in the United Kingdom, the Far East and Australia [8] [11] [29]. To the best of our knowledge, the occurrence of bla IMP genes in E. cloacae isolates is an unusual finding in South Africa.…”

“…MLST data for three isolates was not obtained due to sequencing technicalities, four belonged to ST124, four belonged to ST90, two belonged to a new sequence type and displayed identical allelic profiles and, the remaining two belonged to ST93 and ST108. Relatively little is known about IMP-type MBL-producing E. cloacae with regards to prevalence, risk factors and clinical effects [8] and although our clinical and epidemiological data is scarce some information can be utilised. The specimen types for these infections were fluid/aspirate (n = 5; 33%), pus swab (n = 5; 33%), urine (n = 3; 20%) and catheter tip and sputum (n = 1; 7% each).…”

Dominance of IMP-4-Producing Enterobacter cloacae among Carbapenemase-Producing Enterobacteriaceae in Australia

“…In Australia, IMP-producing Enterobacteriaceae, particularly Enterobacter cloacae, have been reported to be the predominant form of CPE (9)(10)(11). Antibiotic-resistant E. cloacae not only is a common nosocomial pathogen but also has been reported to cause bloodstream infections (10,12). The mortality rate for infections by IMP-producing E. cloacae causing bacteremia can be as high as 40% (12).…”

“…Antibiotic-resistant E. cloacae not only is a common nosocomial pathogen but also has been reported to cause bloodstream infections (10,12). The mortality rate for infections by IMP-producing E. cloacae causing bacteremia can be as high as 40% (12).…”