Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying bothblaIMPandmcr-9genes

Background Carbapenemase-producing Enterobacterales (CPE) are challenging in the healthcare setting, with resistance to multiple classes of antibiotics and a high associated mortality. The incidence of CPE is rising globally, despite enhanced awareness and control efforts. 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. Methods We carried out a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE positive patients. Genomes of IMP-encoding CPE isolates were analysed and overlayed with patient contacts to imply potential transmission events. Results Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli ), of which 86% (72/84) harboured an IncHI2 plasmid, which carried both bla IMP and the mobile colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages which showed significant association with patient contact and movements between four hospital sites and across medical specialities, which had been missed on initial investigations. Conclusions Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of bla IMP CPE, which remained unidentified during standard microbiology and infection control investigations. With DNA sequencing technologies and multi-modal 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 targeted interventions to stop the transmission of resistance within hospital networks. Summary This study describes an investigation, using integrated pathway networks and genomics methods, of the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 in patients across a London regional hospital network, which was missed on routine investigations.