Emerging hypervirulent Klebsiella pneumoniae: Myth, reality, and clinical relevance

The global emergence of hypervirulent Klebsiella pneumoniae (hvKp) has raised concern because of its association with invasive infections and reports of increased mortality. However, recent systematic reviews and meta-analyses reveal a critical paradox: genotypically defined convergent clones and strains carrying fewer virulence-associated markers exhibit mortality rates comparable to, rather than exceeding, those of multidrug-resistant (MDR) K. pneumoniae. In contrast, traditional phenotypic identification preferentially enriches for the classical hypervirulent lineages that remain uniquely associated with metastatic complications. Genome-wide association studies (GWAS) and phenotypic analyses further confirm capsular polysaccharide as a pivotal, plasmid-independent virulence driver in carbapenem-resistant hvKp cohorts, with only 37.3% (22/59) demonstrating true hypervirulence despite universal plasmid marker presence, reinforcing lineage-specific risk over gene carriage alone. The definitional crisis, wherein virulence gene carriage alone fails to predict clinical outcomes, highlights the importance of lineage-specific risk. This is best exemplified by K1/K2 sequence type (ST)23, including clonal group (CG)23-like shadow lineages such as ST65, ST86, ST412 and ST268, which are consistently associated with metastatic disease and adverse outcomes in otherwise healthy hosts. Synthesizing clinical, genomic, and epidemiological evidence, this perspective proposes an updated K. pneumoniae pathotype framework that integrates clonality, antimicrobial resistance (AMR), and epidemiological context; advocates tiered laboratory diagnostics; and cautions against indiscriminate hvKp labelling to safeguard antimicrobial stewardship and informed clinical decision-making.