Phylogenetic lineages and antimicrobial resistance determinants of clinical Klebsiella oxytoca spanning local to global scales

Klebsiella oxytoca is an opportunistic pathogen causing serious nosocomial infections. Knowledge about the population structure and diversity of healthcare-associated K. oxytoca from a genomic standpoint remains limited. Here, we characterized the phylogenetic relationships and genomic characteristics of 20 K. oxytoca sensu stricto isolates recovered from bloodstream infections at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA from 2017 to 2021. Results revealed a diverse population consisting of 15 sequence types (STs) that together harbored 10 variants of the intrinsic beta-lactamase gene bla (OXY-2), conferring resistance to penicillins. Similar sets of antimicrobial resistance (AMR) determinants reside in multiple distinct lineages, with no one lineage dominating the local population. To place the New Hampshire K. oxytoca in a broader context, we compared them to 304 publicly available genomes of clinical isolates from 18 countries. This global clinical K. oxytoca sensu stricto population is represented by over 65 STs that together harbored resistance genes against 14 antimicrobial classes, including eight bla (OXY-2) variants. Three dominant STs in the global population (ST2, ST176, ST199) circulate across multiple countries and were also present in the New Hampshire population. The global K. oxytoca population is genetically diverse, but there is evidence for broad dissemination of a few lineages carrying distinct set of AMR determinants. Our findings reveal the clinical diversity of K. oxytoca sensu stricto and its importance in surveillance efforts aimed at monitoring the evolution of this drug-resistant nosocomial pathogen. IMPORTANCE: The opportunistic pathogen Klebsiella oxytoca has been increasingly implicated in patient morbidity and mortality worldwide, including several outbreaks in healthcare settings. The emergence and spread of antimicrobial resistant strains exacerbate the disease burden caused by this species. Our study showed that clinical K. oxytoca sensu stricto is phylogenetically diverse, harboring various antimicrobial resistance determinants and bla (OXY-2) variants. Understanding the genomic and population structure of K. oxytoca is important for international initiatives and local epidemiological efforts for surveillance and control of drug-resistant K. oxytoca.