Carbapenemase-producing Kluyvera spp.: epidemiology of an evolving species.

BACKGROUND: Kluyvera spp. are increasingly recognised as significant pathogens in humans. Recent reports of carbapenemase-producing (CP) Kluyvera spp. raise a concern that they may be disseminating carbapenemases to other species undetected. Research on CP-Kluyvera spp. is scarce, and little is known about their characteristics. METHODS: We aimed to investigate the epidemiology of CP-Kluyvera spp. in Israel, characterise their antimicrobial resistance and examine mechanisms of transmission of carbapenemase genes. We performed a retrospective epidemiological analysis of all cases of CP-Kluyvera spp. reported to Israel's national surveillance system of carbapenem-resistant Enterobacterales from 2008 to 2023. Hospital-acquired cases were categorized as sporadic or part of an outbreak. Microbiological characterisation of 22 available isolates included antimicrobial susceptibility testing and whole genome sequencing. RESULTS: There were 146 cases of CP-Kluyvera spp. in 2008-2023. 145 were detected in rectal screening samples, and one in a blood culture. The dominant reported species was K. ascorbata (60.3%), followed by K. cryocrescens (24%). The common carbapenemases were KPC (67.1%) and NDM (26.7%). 41.1% of hospital-acquired cases were classified as part of an outbreak.All characterised isolates were multidrug-resistant and produced at least one carbapenemase. Spread of carbapenemase genes in Kluyvera spp. was plasmid-driven by IncC and by Rep-A type plasmids. CONCLUSIONS: Cases of CP-Kluyvera spp. increased annually. Spread of CP-Kluyvera was partially clonal, with both outbreaks and sporadic cases detected. We illustrated that Kluyvera spp. produce a variety of plasmid-borne ARGs, including carbapenemases, which could be horizontally transferred to additional bacterial species, revealing the increasing clinical significance of Kluyvera genus.