Integrated patient network and genomic plasmid analysis reveal a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes

The incidence of carbapenemase-producing Enterobacterales (CPE) is rising globally, yet Imipenemase (IMP) carbapenemases remain relatively rare. This study describes an investigation of the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 in patients across a London regional hospital network. A network analysis approach to patient pathways, using routinely collected electronic health records, identified previously unrecognised contacts between patients who were IMP CPE positive on screening, implying potential bacterial transmission events. Whole genome sequencing of 85 Enterobacterales isolates from these patients revealed that 86% (73/85) were diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli) and harboured an IncHI2 plasmid, which carried both blaIMP and the putative mobile colistin resistance gene mcr-9. Detailed phylogenetic analysis identified two distinct IncHI2 plasmid lineages, A and B, both of which showed significant association with patient movements between four hospital sites and across medical specialities. Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard microbiology and infection control investigations. With whole genome sequencing (WGS) technologies and large-data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Analysing outbreaks at the plasmid level reveals that resistance may be wider spread than suspected, allowing more targetted interventions to stop the transmission of resistance within hospital networks.