Genomic dissection of the bacterial population underlyingKlebsiella pneumoniaeinfections in hospital patients: insights into an opportunistic pathogen

Klebsiella pneumoniaeis 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 ofK. pneumoniaeclinical 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 theK. pneumoniaecomplex (18%). Several infections were caused byK. variicola/K. pneumoniaespecies 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-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 ofK. pneumoniaedisease 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.