Outbreak of IncX8 Plasmid-Mediated KPC-3-Producing Enterobacterales Infection, China

Carbapenem-resistant Enterobacterales (CRE) infection is highly endemic in China; Klebsiella pneumoniae carbapenemase (KPC) 2-producing CRE is the most common, whereas KPC-3-producing CRE is rare. We report an outbreak of KPC-3-producing Enterobacterales infection in China. During August 2020-June 2021, 25 bla_KPC-3-positive Enterobacteriale isolates were detected from 24 patients in China. Whole-genome sequencing analysis revealed that the bla_KPC-3 genes were harbored by IncX8 plasmids. The outbreak involved clonal expansion of KPC-3-producing Serratia marcescens and transmission of bla_KPC-3 plasmids across different species. The bla_KPC-3 plasmids demonstrated high conjugation frequencies (10^-3 to 10^-4). A Galleria mellonella infection model showed that 2 sequence type 65 K2 K. pneumoniae strains containing bla_KPC-3 plasmids were highly virulent. A ceftazidime/avibactam in vitro selection assay indicated that the KPC-3-producing strains can readily develop resistance. The spread of bla_KPC-3-harboring IncX8 plasmids and these KPC-3 strains should be closely monitored in China and globally.