Unraveling the Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Global Epidemiological Landscape and Divergence in Genetic Evolutionary Mechanisms: A Narrative Review

The emergence of hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) poses a critical global health threat, combining extreme antibiotic resistance with increased virulence. This “superbug” evolves via three primary genetic pathways: (i) hypervirulent K. pneumoniae acquiring carbapenem resistance plasmids, (ii) carbapenem-resistant K. pneumoniae acquiring virulence plasmids, and (iii) classical K. pneumoniae integrating resistance and virulence genes through fusion plasmids. Globally, Hv-CRKP exhibits multiregional dissemination, with particular prevalence in Asia, where China serves as one of the major epicenters dominated by the sequence type (ST) 11 clone, in contrast to the predominance of the ST258 clone in Europe and the Americas. Its virulence is orchestrated by multiple factors, including capsule polysaccharides, siderophore systems, the colibactin genotoxin and the Peg-344 protein. Resistance mechanisms involve carbapenemase expression, outer membrane porin mutations and efflux pump overexpression. The synergistic evolution of virulence and resistance in Hv-CRKP poses significant challenges to clinical antimicrobial therapy, necessitating the development of novel intervention strategies and innovative antimicrobial approaches. This review focuses mainly on the genetic evolution, global epidemiological variations and underlying drivers, virulence determinants and resistance mechanisms of Hv-CRKP. Furthermore, this review explores the evolution and divergence of its biological characteristics, providing critical insights for future research and clinical practice to combat this escalating global public health crisis.