Understanding carbapenem-resistant hypervirulent Klebsiella pneumoniae: Key virulence factors and evolutionary convergence

The emergence of hypervirulence (hv) and carbapenem resistance (CR) as distinct evolutionary directions for Klebsiella pneumoniae presents a significant threat in clinical settings. However, in recent years, there has been a growing identification of K. pneumoniae strains that integrate both phenotypes, resulting in severe clinical outcomes. Carbapenem-resistant hypervirulent K. pneumoniae (CRhvKP) typically emerges through the acquisition of plasmids carrying either virulence or CR-encoded genes by carbapenem-resistant K. pneumoniae or hypervirulent K. pneumoniae. Furthermore, the acquisition of a hybrid plasmid can confer a combination of CR and hv. CRhvKP can cause a variety of infections, including pneumonia, urinary tract infections, bloodstream infections, liver abscesses, and other related conditions. While the sequence type 11 (ST11) dominates the majority of CRhvKP strains in China, the molecular factors responsible for the success of ST11 CRhvKP largely remain unknown. Here, we provide an overview of the current understanding of the variation and distribution of crucial virulence determinants, the mechanisms driving the merging of hv and CR, and the potential molecular factors influencing the epidemiological success of ST11 CRhvKP. This research aims to contribute to a comprehensive understanding of the complexities surrounding CRhvKP. It is imperative to underscore the development of combination therapies, precision medicine, and vaccine strategies as pivotal approaches in effectively combating CRhvKP. Considering the widespread prevalence of CRhvKP, a prioritized, multifaceted approach encompassing infection control, active surveillance, and the development of innovative therapeutics is essential.