O2a O-antigen type and sepsis in invasive Klebsiella pneumoniae: evidence of association and clustering with an ST11-K64/CRKP background in a retrospective cohort

Background Invasive Klebsiella pneumoniae (KP) infections complicated by sepsis are often associated with substantial mortality, which may partly result from dysregulated host immune–inflammatory responses to bacterial components, including lipopolysaccharide. KP O-antigen types have gained increasing attention in epidemiological surveillance and vaccine development, yet their relationship with sepsis risk in invasive KP infection remains insufficiently evaluated, particularly given potential confounding by clonal background and antimicrobial resistance. Here, we integrated clinical data with pathogen genomic and phenotypic characteristics to identify factors associated with sepsis in invasive KP infection and to characterize the underlying clonal and resistance context. Methods This retrospective cohort study screened all consecutive patients with culture-confirmed KP infection at Qingdao Municipal Hospital (November 2016–October 2023) and identified invasive cases based on isolation from normally sterile sites; only the first invasive episode per patient was included. Sepsis was defined according to Sepsis-3 criteria. Antimicrobial susceptibility testing was performed routinely, and resistance phenotypes (CRKP/ESBL/MDR) were derived from susceptibility results. All isolates underwent whole-genome sequencing (paired-end 150 bp) on the MGI Tech MGISEQ-2000 platform; serotypes, sequence types, and virulence determinants were inferred using Kleborate. Core-genome SNP phylogenies were reconstructed using Snippy with recombination filtered by Gubbins and maximum-likelihood inference by IQ-TREE. Multivariable logistic regression was used to identify factors associated with sepsis. Results Among 127 patients with invasive KP infection, the incidence of sepsis was 55.1% (70/127). In prespecified multivariable logistic regression models, bloodstream infection, higher PCT levels, and lymphocyte counts