Genomic analyses identify nosocomial transmission of ST23 carbapenem-resistant hypervirulent Klebsiella pneumoniae mediated by a conjugative IncFII K2 NDM-1 plasmid

The World Health Organization has identified ST23 carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) as a critical public health threat. Through China’s national surveillance system (BRICS), we identified and characterized ST23 CR-hvKP bloodstream isolates from 2019–2023. Among 1069 CRKP bloodstream isolates, four ST23-K1 strains (0.37%) were detected across two hospitals, including a nosocomial transmission pair (differing by only 2 core SNPs). Clinical outcomes revealed that three of the four patients achieved recovery following appropriate antibiotic therapy, with one mortality case attributed to underlying comorbidities. All four ST23 isolates demonstrated resistance to multiple antibiotics, indicating a pattern of multidrug resistance. Genomic analysis uncovered diverse resistance mechanisms: the nosocomial transmission pair possessed conjugative IncFIIK2 NDM-1 plasmids, while the others harbored conjugative IncFIIK34 KPC-2 plasmids, which exhibited reduced carbapenem resistance attributed to the downregulation of blaKPC-2 expression. Conjugation assays revealed high transferability (10−5 for IncFIIK2 NDM-1; 10−4 for IncFIIK34 KPC-2). Whole-plasmid comparative genomics analysis suggested that the IncFIIK2 NDM-1 plasmids shared > 99% identity with historical IncFIIK2 plasmid backbones from Chinese K. pneumoniae isolates (2014–2022), suggesting local evolution. Notably, only 4.4% (26/590) of global IncFIIK2 plasmids carried blaNDM-1 and all IncFIIK2 NDM-1 plasmids maintain conjugative potential. All strains harbored conserved virulence plasmids and maintained hypervirulence, as indicated by a mouse infection model, with the exception of one strain that exhibited cps mutations. This study reports the first genomic evidence of a high-frequency conjugative IncFIIK2 NDM-1 plasmid in a hospital-transmitted ST23 CR-hvKP clone, highlighting the need for plasmid-focused surveillance to control this potential threat.