Long-read sequencing reveals genomic diversity and associated plasmid movement of carbapenemase-producing bacteria in a UK hospital over 6 years

Healthcare-associated infections (HCAIs) affect the most vulnerable people in society and are increasingly difficult to treat in the face of mounting antimicrobial resistance (AMR). Routine surveillance represents an effective way of understanding the circulation and burden of bacterial resistance and transmission in hospital settings. Here, we used whole-genome sequencing (WGS) to retrospectively analyse carbapenemase-producing Gram-negative bacteria from a single hospital in the UK over 6 years (n=165). We found that the vast majority of isolates were either hospital-onset (HAI) or HCAI. Most carbapenemase-producing organisms were carriage isolates, with 71 % isolated from screening (rectal) swabs. Using WGS, we identified 15 species, the most common being Escherichia coli and Klebsiella pneumoniae. Only one significant clonal outbreak occurred during the study period and involved a sequence type (ST)78 K. pneumoniae carrying bla_NDM-1 on an IncFIB/IncHI1B plasmid. Contextualization with public data revealed little evidence of this ST outside of the study hospital, warranting ongoing surveil-lance. Carbapenemase genes were found on plasmids in 86 % of isolates, the most common types being bla_NDM-and bla_OXA-type alleles. Using long-read sequencing, we determined that approximately 30 % of isolates with carbapenemase genes on plas-mids had acquired them via horizontal transmission. Overall, a national framework to collate more contextual genomic data, particularly for plasmids and resistant bacteria in the community, is needed to better understand how carbapenemase genes are transmitted in the UK.