Abstract
An outbreak of an ertapenem-resistant Klebsiella pneumoniae clone occurred in a specialist children's hospital in Liverpool, United Kingdom (UK), from April 2022 to February 2023. Carbapenem-resistant K. pneumoniae is unusual in the UK, and identification of two isolates exhibiting ertapenem resistance in the same ward in December 2022 raised concerns and triggered an outbreak investigation. Potential transmission through shared equipment was identified; a total of 11 patients were colonised and/or infected by phenotypically similar isolates. Multilocus sequence typing supported hospital transmission, and short-read whole genome sequencing (WGS) was performed on all isolates; long-read sequencing was conducted for three isolates to confidently resolve the plasmid structure. WGS confirmed a clonal outbreak and strongly supported the suspected nosocomial transmission. Detailed analysis of the resistance determinants indicated that ertapenem resistance was driven by a combination of different beta-lactamases, which would not alone convey this resistance profile, along with modifications in porin structure that suggested a synergistic interaction. These findings highlight how highly resistant strains could be mislabelled as predicted sensitive when considering genetic determinants in isolation and underscore the need to study beta-lactam resistances beyond the presence or absence of specific genes but also to consider co-occurrence.