Rapid emergence, transmission, and evolution of KPC and NDM coproducing carbapenem-resistant Klebsiella pneumoniae

Due to the limited treatment options, the widespread of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a serious clinical challenge. The emergence of Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM) coproducing CRKP (KPC-NDM-CRKP) further aggravates this issue. In this study, we identified 15 KPC-2-NDM-5-CRKPs as being responsible for an outbreak that involved 10 patients from October 2020 to May 2021. The outbreak was sustained by ST11-KL47-OL101 KPC-2-NDM-5-CRKPs, which exhibited non-susceptible to all antimicrobials available in mainland China. Of these strains, we characterized a conjugative hybrid plasmid co-harboring bla_KPC-2 and bla_NDM-5 with high stability. Plasmid comparison and phylogenetic analysis were performed to investigate the origin of the hybrid plasmid and its fusion mechanism. It was speculated that the hybrid plasmid might originate from Klebsiella pneumoniae subsp. pneumoniae strain kpn-hnqyy plasmids unnamed1 (encoding NDM-5) and unnamed2 (encoding KPC-2). The fusion of these two plasmids was presumably mediated by IS26. Global genomic surveillance raised an alarm about the increased prevalence of KPC-NDM-CRKPs. Phylogenetic evaluation was carried out with a total of 327 KPC-NDM-CRKP genomes to provide a global perspective on such strains, and potential transmission events in other global regions were also observed during the COVID-19 period. The outbreak of such strains in the real world and the co-transfer of bla_KPC and bla_NDM would exacerbate the dispersal of KPC-NDM-CRKPs, which poses a severe threat to public health.