Genomic dissection of the bacterial population underlying Klebsiella pneumoniae infections in hospital patients: insights into an opportunistic pathogen

Abstract

AbstractKlebsiella pneumoniae is a major cause of opportunistic healthcare-associated infections, which are increasingly complicated by the presence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance. We conducted a year-long prospective surveillance study of K. pneumoniae clinical isolates identified in a hospital microbiological diagnostic laboratory. Disease burden was two-thirds urinary tract infections (UTI; associated with female sex and age), followed by pneumonia (15%), wound (10%) and disseminated infections/sepsis (10%). Whole-genome sequencing (WGS) revealed a diverse pathogen population, including other species within the K. pneumoniae complex (18%). Several infections were caused by K. variicola/K. pneumoniae species hybrids, one of which showed evidence of nosocomial transmission, indicating fitness to transmit and cause disease despite a lack of acquired antimicrobial resistance (AMR). A wide range of AMR phenotypes were observed and, in most cases, corresponding mechanisms were identified in the genomes, mainly in the form of plasmid-borne genes. ESBLs were correlated with presence of other acquired AMR genes (median 10). Bacterial genomic features associated with nosocomial onset of disease were ESBL genes (OR 2.34, p=0.015) and rhamnose-positive capsules (OR 3.12, p<0.001). Virulence plasmid-encoded features (aerobactin, hypermucoidy) were rare (<3%), and mostly present in community-onset cases. WGS-confirmed nosocomial transmission was rare (10% of cases) but strongly associated with ESBLs (OR 21, p<1×10-11). We estimate 28% risk of onward nosocomial transmission for ESBL-positive strains vs 1.7% for ESBL-negative strains. These data indicate the underlying burden of K. pneumoniae disease in hospitalised patients is due largely to opportunistic infections with diverse strains. However, we also identified several successful lineages that were overrepresented but not due to nosocomial transmission. These lineages were associated with ESBL, yersiniabactin, mannose+ K loci and rhamnose- K loci; most are also common in public clinical genome collections, suggesting enhanced propensity for colonisation and spread in the human population.