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

Abstract Objectives The aim of this study was to determine the genetic and epidemiological properties of Pseudomonas aeruginosa strains producing VIM-type metallo-β-lactamases (MBLs) isolated from patients in Japan. Methods A total of 1,860 clinical isolates of carbapenem-resistant P. aeruginosa were obtained from patients hospitalized in Japan from 2012 to 2018. The blaVIMs-positive isolates were screened by polymerase chain reaction. Antimicrobial susceptibility was tested using the broth microdilution method. The whole genomes of these isolates were sequenced by a next generation sequencer, and the phylogenetic analysis was constructed from single nucleotide polymorphism concatemers. Multilocus sequence types were deduced and drug resistance genes were identified using whole genome sequence data. Results Of 1,860 isolates, 25 blaVIMs-positive isolates were screened in 9 medical settings in Japan. The population of VIM-producing P. aeruginosa was significantly increased between 2012 and 2018. All 25 blaVIMs-positive isolates were resistant to imipenem, meropenem and ciprofloxacin, but sensitive to colistin. These isolates harbored blaVIM-1, blaVIM-2, blaVIM-24, blaVIM-60 or the novel variant blaVIM-66, and belonged to 4 different sequence types (STs), including ST179, ST233, ST235 and ST1816. Of them, the 11 isolates harboring blaVIM-24, blaVIM-60 or blaVIM-66 were obtained from a single hospital, with all belonging to ST1816. The VIM-24, VIM-60 and VIM-66 had an amino acid substitutions (Arg228Leu) compared with VIM-2. Conclusions The numbers of P. aeruginosa strains producing VIM-type MBLs has increased in medical settings in Japan. P. aeruginosa ST1816 producing VIMs with Arg228Leu have emerged and evolved in a medical setting in Japan.