Definitional ambiguity and the dual threat of Hypervirulent Klebsiella pneumoniae infections: a systematic review and meta-analysis

Background: Hypervirulent Klebsiella pneumoniae (HvKp) causes severe invasive infections, but the lack of a standardized definition complicates surveillance. The emergence of carbapenem-resistant HvKp (CR-HvKp) poses a “dual-risk” threat whose impact is poorly quantified. This meta-analysis aimed to determine pooled proportions of severe outcomes stratified by diagnostic criteria and quantify the mortality risk associated with CR-HvKp. Methods: Following PRISMA guidelines, we systematically searched five databases for studies published up to July 2025 reporting clinical outcomes of HvKp infection. A random-effects model was used to calculate pooled proportions of liver abscess, metastatic spread, septic shock, microbiological failure and mortality, with subgroup analyses by HvKp definition (phenotypic, molecular, combined, or clinical). Odds ratios (OR) for mortality in CR-HvKp versus carbapenem-susceptible (CS)-HvKp were pooled. Results: From 4413 records, 79 studies involving 4240 patients were included. The pooled proportion of liver abscess was 24% (95% CI 17–32%) and metastatic spread was 22% (95% CI 12–32%), both significantly influenced by the diagnostic criteria used (p < 0.0001). Pooled mortality for HvKp was 21% (95% CI 15–27%). In stark contrast, pooled mortality for CR-HvKp was 57% (95% CI 35–78%). The frequency of microbiological failure among HvKp infected patients was reported to be 39%. A meta-analysis of six studies revealed CR-HvKp infection was associated with over 12-fold higher odds of death compared to CS-HvKp infection. Conclusion: HvKp continues to cause severe invasive infections, though outcome estimates vary due to inconsistent definitions. Mortality increases markedly when carbapenem resistance co-exists with virulence, indicating that poor outcomes are driven by both pathogenic and resistance mechanisms. Standardized diagnostic criteria and expanded genomic surveillance are essential to improve epidemiological comparability and guide early detection and containment of high-risk HvKp strains.