William C. Shropshire

Despite the notable clinical impact, recent molecular epidemiology regarding third-generation-cephalosporin-resistant (3GC-R) Klebsiella pneumoniae in the USA remains limited. We performed whole-genome sequencing of 3GC-R K. pneumoniae bacteraemia isolates collected from March 2016 to May 2022 at a tertiary care cancer centre in Houston, TX, USA, using Illumina and Oxford Nanopore Technologies platforms. A comprehensive comparative genomic analysis was performed to dissect population structure, transmission dynamics and pan-genomic signatures of our 3GC-R K . pneumoniae population. Of the 178 3GC-R K. pneumoniae bacteraemias that occurred during our study time frame, we were able to analyse 153 (86 %) bacteraemia isolates, 126 initial and 27 recurrent isolates. While isolates belonging to the widely prevalent clonal group (CG) 258 were rarely observed, the predominant CG, 307, accounted for 37 (29 %) index isolates and displayed a significant correlation (Pearson correlation test P value=0.03) with the annual frequency of 3GC-R K . pneumoniae bacteraemia. Interestingly, only 11 % (4/37) of CG307 isolates belonged to the commonly detected ‘Texas-specific’ clade that has been observed in previous Texas-based K. pneumoniae antimicrobial-resistance surveillance studies. We identified nearly half of our CG307 isolates ( n =18) belonged to a novel, monophyletic CG307 sub-clade characterized by the chromosomally encoded bla SHV-205 and unique accessory genome content. This CG307 sub-clade was detected in various regions of the USA, with genome sequences from 24 additional strains becoming recently available in the National Center for Biotechnology Information (NCBI) SRA database. Collectively, this study underscores the emergence and dissemination of a distinct CG307 sub-clade that is a prevalent cause of 3GC-R K . pneumoniae bacteraemia among cancer patients seen in Houston, TX, and has recently been isolated throughout the USA.