Abstract The global spread of hypervirulent Klebsiella pneumoniae (hvKp) poses a serious public health threat. In this study, we conducted genomic epidemiology analysis on 2097 global hvKp isolates, including our 900 isolates sequenced through the Illumina platform (177 of them fully sequenced through PacBio platform), representing the most comprehensive genomic analysis of hvKp to date. Our results identified six dominant clonal groups (CGs), particularly including CG23 and CG258, and 17 major virulence determinant combinations (VDCs) comprising 10 virulence gene profiles (VGPs), four types of virulence plasmids, four ICEKp variants, Tn7399, and all_island. Each CG harbored distinct advantageous VDCs, indicating strong genomic correlation and co‐evolution. Additionally, the phylogeny and evolutionary history of CG23 and CG258 were characterized in depth. Notably, 41.58% of the 2097 isolates were multidrug‐resistant and 33.29% were carbapenem‐resistant, indicating serious antimicrobial resistance. Overall, our study provides a global genomic landscape of hvKp, emphasizing the genetic basis for their global dissemination and the need for precise prevention and control.
