Dissecting the host-plasmid interplay to unravel the spread of ESBL-producing K. pneumoniae

ABSTRACT Multidrug-resistant Klebsiella pneumoniae (Kp) infections, especially carbapenem resistant (CR-Kp) and extended spectrum β-lactamase (ESBL-Kp) producing strains, have become successful global pathogens that are recalcitrant to most effective antibiotics and are associated with high rates of morbidity and mortality. Extensive molecular epidemiological studies over the last 20 years described the successful global spread of CR-Kp ST258, but improved diagnostics and treatment have calmed this epidemic. In this background, we have investigated the increase and national spread of ESBL-Kp isolates, especially in the community, by partnering with Quest Diagnostics who captured 1,338 ceftriaxone resistant from 10 regional sites for whole genome sequencing. The collected population, primarily from community patients (>85%), were cultured from elderly (mean age 70) women (68%) with urinary tract infections (92%). These isolates showed 53% resistance to cefepime, 33% resistance to piperacillin/tazobactam and of clinical significance, 89% were resistant to fluroquinolones, 85% were resistant to trimethoprim/sulfamethoxazole, and 86% were resistant to nitrofurantoin; oral agents commonly used to treat UTIs. In contrast to the CR-Kp ST258 epidemic, 1,338 ESBL-Kp isolates revealed remarkable genetic diversity, 199 sequence types (STs) and 104 capsule polysaccharides (CPS) were identified, and 81% harbored multidrug resistant IncF transferable plasmids. Most significantly, genomic and plasmid dissection of the major STs and CPS types identified transmissible clusters with highly conserved genomes (