Epidemiology of KPC-producing Enterobacterales isolated from 2019 to 2023 in France.

OBJECTIVES: The global spread of Klebsiella pneumoniae carbapenemase (KPC)-type carbapenemases has historically been driven by clonal group CG258, but increasing clonal diversification has recently been reported. We aimed to provide a comprehensive phenotypic and genomic characterization of KPC-producing Enterobacterales referred to French National Center (NRC) for Antimicrobial Resistance between 2019 and 2023. MATERIALS AND METHODS: A total of 419 KPC-producing Enterobacterales were referred to the French NRC for Antimicrobial Resistance. Antimicrobial susceptibility testing was performed by broth microdilution. Whole-genome sequencing was conducted for 404 isolates. AMR gene detection, MLST and SNP-based phylogeny were used to analyse resistance mechanisms, clonal structure and outbreak dynamics. RESULTS: KPC-producing Enterobacterales accounted for ∼2% of all carbapenemase-producing Enterobacterales. The K. pneumoniae species complex represented 86% (363/419) of isolates. KPC-3 predominated (328/419, 78%), followed by KPC-2 (87/419, 21%). Additional carbapenemases were detected in 11 isolates. Ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam showed high in vitro activity (97.8%, 95.8% and 97.9% susceptibility, respectively). MLST of 353 K. pneumoniae genomes identified 45 sequence types (STs); ST307 predominated (39.4%) and was associated with a major outbreak in northern France. ST147 (8.8%) and ST512 (7.6%) were also prevalent. Fifteen isolates from ST11, ST39, ST101, and ST395 had high virulence score of 4 (iuc-positive). CONCLUSIONS: KPC-producing K. pneumoniae referred to the French NRC show marked clonal diversification. The emergence of resistant isolates and convergent resistance-virulence profiles underscore the need for sustained genomic surveillance.