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-β-lactamases isolated from patients in Japan.

METHODS

A total 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 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 bla-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 bla-positive isolates were resistant to imipenem, meropenem and ciprofloxacin but were susceptible to colistin. The isolates harboured bla, bla, bla, bla or the novel variant bla and belonged to four different sequence types (STs), including ST179, ST233, ST235 and ST1816. The 11 isolates harbouring bla, bla or bla 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.