Convergence of carbapenem resistance and hypervirulence in Klebsiella pneumoniae in Europe: a systematic review

The convergence of hypervirulence and carbapenem resistance in Klebsiella pneumoniae (hv-CRKP) is an emerging public health threat. Although extensively reported in Asia, these strains are increasingly identified in Europe, where their epidemiology and underlying convergence mechanisms remain insufficiently characterized. We aimed to describe the circulation of hv-CRKP in Europe, their molecular characteristics, and the main mechanisms underlying the convergence of resistance and hypervirulence. We performed a systematic literature review using PubMed and identified studies published up to 31 October 2024 reporting hv-CRKP isolates from human samples in Europe. Hypervirulence was defined using genomic criteria (major virulence genes or Kleborate score ≥3) and/or a highly suggestive clinical presentation. A total of 419 isolates from 30 studies were analyzed. hv-CRKP isolates were identified in 14 European countries, with major epidemic clusters reported in Italy and Germany. In contrast to the Asian epidemiology dominated by ST11-KPC-producing clones, the European landscape showed marked clonal diversity, mainly involving ST147, ST23, ST307 and ST395. NDM was the predominant carbapenemase type (75.4%, 316/419) alone or in combination with other carbapenemases, followed by OXA-48-like enzymes (37.7%, 158/419). Hybrid plasmids derived from pNDM-MAR-like backbones emerged as key drivers of convergence by enabling co-transfer of virulence and resistance determinants. hv-CRKP are increasingly reported in Europe, mainly through multidrug-resistant hospital-adapted clones acquiring virulence determinants. Their epidemic potential, combined with imperfect genotype-phenotype correlation, complicates identification and challenges historical definitions of hypervirulence. Surveillance strategies should move beyond resistance alone and integrate virulence markers to enable earlier detection and prevent nosocomial spread.