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

Abstract 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.