Emergence and spread of VIM-type metallo-β-lactamase-producing Pseudomonas aeruginosa clinical isolates in Japan

Objectives: The aim of this study was to determine the genetic and epidemiological properties of Pseudomonas aeruginosa strains producing VIM-type metallo-p-lactamases isolated from patients in Japan. Methods: Atotal of 1860 clinical isolates of carbapenem-resistant P. aeruginosa were obtained from patients hospitalised in Japan from 2012-2018. Carbapenem-resistant P. aeruginosa isolates were screened for bla(VIM) genes by PCR. Antimicrobial susceptibility was determined by the broth microdilution method. The whole genomes of these isolates were sequenced using a next-generation sequencer, and phylogenetic analysis was performed using single nucleotide polymorphism concatemers. Multilocus sequence typing (MLST) was performed and drug resistance genes were identified using whole-genome sequence data. Results: Of 1860 isolates, 25 blavim-positive isolates were screened in nine medical settings in Japan. The population of VIM-producing P. aeruginosa significantly increased between 2012 and 2018. All 25 blavimpositive isolates were resistant to imipenem, meropenem and ciprofloxacin but were susceptible to colistin. The isolates harboured bla(VIM-1), blav(VIM-1), bla(VIM-24), bla(VIM-60) or the novel variant bla(VIM-66) and belonged to four different sequence types (STs), including ST179, ST233, ST235 and ST1816. The 11 isolates harbouring bla(VIM-24), bla(VIM-60) or bla(VIM-66) were obtained from a single hospital, all belonging to ST1816. VIM-24, VIM-60 and VIM-66 had an amino acid substitution (Arg228Leu) compared with VIM-2. Conclusions: The number of P. aeruginosa strains producing VIM-type MBLs has increased in medical settings in Japan. Pseudomonas aeruginosa ST1816 producing VIM enzymes with Arg228Leu substitution have emerged and evolved in a medical setting in Japan. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.