Revisiting definitions of hypervirulent and classical Klebsiella pneumoniae through virulence factors and disease phenotype

BACKGROUND: Hypervirulent Klebsiella pneumoniae (hvKP) has been described as an invasive syndrome of liver abscess and metastatic infection in Asia, and this syndrome is emerging globally. METHODS: This study examined the association between disease phenotypes and genotypic markers of hypervirulence in 273 isolates of Klebsiella pneumoniae (KP) collected from invasive infections across three hospitals in Hong Kong between 2019 and 2023. Whole genome sequencing was analysed by Kleborate and Kaptive. Epidemiological background, disease phenotype, virulence genes, and antimicrobial susceptibility were analysed. Genotypically defined hvKP (g-hvKP) were defined as having iucA, iroB, rmpA, rmpA2, and peg-344. Others were defined as classical Klebsiella pneumoniae (cKP). Genome-wide association study (GWAS) was performed to identify additional genes associated with hvKP. RESULTS: The commonest K types are K2 (13.9%) and K1 (10.6%). The commonest ST is ST 23 (8.8%). g-hvKP represents 20.8% of all isolates. The ESBL phenotype is more likely in cKP than g-hvKP (22% vs 9%, p = 0.04). g-hvKP are more susceptible to cephalosporins (p = 0.02) and fluoroquinolones (p = 0.01). Among liver abscess cases, 49% of them are c-KP. g-hvKP is associated with neither mortality, disease severity, nor metastatic infection. g-hvKP has a sensitivity of 46% and a specificity of 86% in detecting liver abscesses or metastatic infections. By omitting rmpA2, F1 score improves from 0.46 to 0.51. GWAS reveals cysH3, pfeA2, and aidA as additional candidate genes linked to hvKP. CONCLUSION: Significant overlap in disease phenotype exists between cKP and g-hvKP. Additional candidate genes linked to hvKP are cysH3, pfeA2, and aidA.