Molecular and epidemiological analysis of IMP-1 metallo-β-lactamase-producing Klebsiella pneumoniae in a tertiary care hospital in Japan

Abstract

This study investigated the molecular and phenotypic characteristics of carbapenemase-producing Klebsiella pneumoniae, and identified the risk factors underlying its acquisition. We evaluated K. pneumoniae isolated in Nagasaki University Hospital between January 2009 and June 2015. The presence of carbapenemase genes and plasmid characteristics were investigated. We performed multilocus sequence typing (MLST), and generated a dendrogram based on the results of pulsed-field gel electrophoresis (PFGE) for carbapenemase-producing strains. We also performed a case-control study of patients. Of the 88 K. pneumoniae strains that showed minimum inhibitory concentration 1 mg/mL for imipenem and/or meropenem, and that were available from our bacterial collection, 18 had the IMP-type carbapenemase gene, all of which were IMP-1 according to sequencing analysis. Strains included seven different sequence types (STs), of which the most common was ST1471. A dendrogram showed the significant similarity of some strains with relationships in PFGE patterns, STs, and the wards in which they were isolated. Plasmid incompatibility group was similar among the IMP-1 producers. Regarding risk factors, multivariate analysis showed that liver disease and previous uses of carbapenems and anti-fungal drugs were significant factors for the acquisition of IMP-1-producing strains. Our results demonstrate that IMP-1 is a major carbapenemase produced by K. pneumoniae. The PFGE results indicated the possibility of transmission in the hospital. The identified risk factors should be considered for appropriate antibiotic therapy and infection-control measures.

Efficacy of meropenem and amikacin combination therapy against carbapenemase-producing Klebsiella pneumoniae mouse model of pneumonia

“…We tried other clinical isolates, but the pathogenicity was weak, and it was difficult to create pneumonia stably. This KP2 strain possesses IMP-1 carbapenemase, which is the most dominant type in Japan [13]. It is known that different types of carbapenemase hydrolyze carbapenems to different degrees, thereby exhibiting variations in antimicrobial resistance [25].…”

“…It is known that different types of carbapenemase hydrolyze carbapenems to different degrees, thereby exhibiting variations in antimicrobial resistance [25]. For example, most of the strains harboring IMP-1 carbapenemase exhibit susceptibility to aminoglycosides [13], while NDM-1 carbapenemase possessing strains often show high levels of resistance against aminoglycosides [26]. Hence, careful attention is required in applying these results to clinical situations.…”

“…In preliminary experiments for developing the mouse model, a total of eighteen clinically isolated CR-Kp in Nagasaki University Hospital between January 2009 and June 2015 [13] were screened in four kinds of mice strains (BALB/c, C57/BL6, ddY, and ICR) by instilling saline-based inoculum into their tracheas. Among them, the strain named KP2 showed the strongest pathogenicity against BALB/c, though the infection was inconsistent and lacked reproducibility.…”

“…Therefore, we decided to inoculate using an agar-based inoculum method, using the KP2 strain. This strain has been confirmed to have IMP-1 gene and produce carbapenemase [13]. The bacteria were stored at À80 C in a Microbank® bead preservation system (Pro-Lab Diagnostics, Ontario, CA) until use.…”

Bactericidal Efficacy of Meropenem in Combination with Cefmetazole against IMP-producing Carbapenem-Resistant Enterobacteriaceae

“…Of these, NDM producers have rapidly spread worldwide since the first reports of their emergence in 2009 [1]. Despite their global dissemination, KPCs, OXAs, and NDMs are still not common in Japan, where IMP-1 and IMP-6 are the exclusively predominant carbapenemases [2,3].…”