Integrated Analysis of Patient Networks and Plasmid Genomes to Investigate a Regional, Multispecies Outbreak of Carbapenemase-Producing Enterobacterales Carrying Both blaIMP and mcr-9 Genes.

Autor:	Wan Y; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom., Myall AC; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; Department of Mathematics, Imperial College London, London, United Kingdom., Boonyasiri A; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand., Bolt F; Department of Infectious Diseases, Imperial College Healthcare NHS Trust, London, United Kingdom.; Centre for Antimicrobial Optimisation, Hammersmith Hospital, Imperial College London, London, United Kingdom.; Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom., Ledda A; Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom.; HCAI, Fungal, AMR, AMU and Sepsis Division, UK Health Security Agency, London, United Kingdom., Mookerjee S; Department of Infectious Diseases, Imperial College Healthcare NHS Trust, London, United Kingdom., Weiße AY; School of Biological Sciences, University of Edinburgh, Scotland, United Kingdom.; School of Informatics, University of Edinburgh, Scotland, United Kingdom., Getino M; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom., Turton JF; HCAI, Fungal, AMR, AMU and Sepsis Division, UK Health Security Agency, London, United Kingdom., Abbas H; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; Department of Microbiology, North West London Pathology, London, United Kingdom., Prakapaite R; MRC Centre for Molecular Bacteriology and Infection, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom., Sabnis A; MRC Centre for Molecular Bacteriology and Infection, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom., Abdolrasouli A; Department of Infectious Diseases, Imperial College Healthcare NHS Trust, London, United Kingdom., Malpartida-Cardenas K; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; Centre for Bio-Inspired Technology, Department of Electrical and Electronic Engineering, Faculty of Engineering, Imperial College London, London, United Kingdom., Miglietta L; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; Centre for Bio-Inspired Technology, Department of Electrical and Electronic Engineering, Faculty of Engineering, Imperial College London, London, United Kingdom., Donaldson H; Department of Microbiology, North West London Pathology, London, United Kingdom., Gilchrist M; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; Department of Infectious Diseases, Imperial College Healthcare NHS Trust, London, United Kingdom., Hopkins KL; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; HCAI, Fungal, AMR, AMU and Sepsis Division, UK Health Security Agency, London, United Kingdom., Ellington MJ; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; Reference Services Division, UK Health Security Agency, London, United Kingdom., Otter JA; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom., Larrouy-Maumus G; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, United Kingdom., Edwards AM; MRC Centre for Molecular Bacteriology and Infection, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom., Rodriguez-Manzano J; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; Centre for Antimicrobial Optimisation, Hammersmith Hospital, Imperial College London, London, United Kingdom.; Centre for Bio-Inspired Technology, Department of Electrical and Electronic Engineering, Faculty of Engineering, Imperial College London, London, United Kingdom., Didelot X; School of Life Sciences and Department of Statistics, University of Warwick, Coventry, United Kingdom., Barahona M; Department of Mathematics, Imperial College London, London, United Kingdom., Holmes AH; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; Department of Infectious Diseases, Imperial College Healthcare NHS Trust, London, United Kingdom.; Centre for Antimicrobial Optimisation, Hammersmith Hospital, Imperial College London, London, United Kingdom., Jauneikaite E; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom., Davies F; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.; Department of Infectious Diseases, Imperial College Healthcare NHS Trust, London, United Kingdom.; Department of Microbiology, North West London Pathology, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2024 Jul 25; Vol. 230 (1), pp. e159-e170.
DOI:	10.1093/infdis/jiae019
Abstrakt:	Background: Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of imipenemase (IMP)-encoding CPE among diverse Enterobacterales species between 2016 and 2019 across a London regional network. Methods: We performed 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 overlaid with patient contacts to imply potential transmission events. Results: Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, and Escherichia coli); 86% (72 of 84) harbored an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68 of 72). Phylogenetic analysis of IncHI2 plasmids identified 3 lineages showing significant association with patient contacts and movements between 4 hospital sites and across medical specialties, which was missed in initial investigations. Conclusions: Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multimodal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.SummaryThis was an investigation, using integrated pathway networks and genomics methods, of the emergence of imipenemase-encoding carbapenemase-producing Enterobacterales among diverse Enterobacterales species between 2016 and 2019 in patients across a London regional hospital network, which was missed on routine investigations. Competing Interests: Potential conflicts of interest. A. C. M. is a majority shareholder in a NEXT Q company that is developing technology support systems for IPC. M. Gi. has received honoraria from Pfizer and Menarini Pharmaceuticals. J. F. T. holds shares in Oxford Nanopore Technologies. K. L. H. has received grant money from Shionogi and consulting fees from Cepheid. J. A. O. has received consulting fees from Gama Healthcare, Biointerations, Spectrum X, and Ondine. All other authors report no potential conflicts. Funding to pay the Open Access publication charges for this article was provided by Imperial College London. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze:	MEDLINE
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