Abstract
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 blaIMP 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 blaIMPCPE, 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.
Competing Interest Statement
JT holds some shares in Oxford Nanopore Technologies. All other authors have nothing to declare.
Funding Statement
This work was supported in part by the faculty of medicine, Siriraj hospital, Mahidol university, Thailand (awarded to AB) and Medical Research Council Clinical Academic Research Fellowship scheme (awarded to FD, grant number MR/T005254/1).
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
This study was carried out in accordance with ethics reference 21/LO/0170 (279677), protocol 21HH6538 Investigation of epidemiological and pathogenic factors associated with infectious diseases.
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Footnotes
To update genomic analysis, patient network analysis. The main message and findings did not change.