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

IMP carbapenemase carbapenem-resistant Enterobacterales horizontal gene transfer patient pathways spatiotemporal network

Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
20 Jan 2024
Historique:
received: 19 09 2023
revised: 02 01 2024
accepted: 19 01 2024
medline: 21 1 2024
pubmed: 21 1 2024
entrez: 21 1 2024
Statut: aheadofprint

Résumé

Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. 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 overlayed with patient contacts to imply potential transmission events. Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli); 86% (72/84) harboured an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages showing significant association with patient contacts and movements between four hospital sites and across medical specialities, which was missed on initial investigations. 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 multi-modal 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.

Sections du résumé

BACKGROUND BACKGROUND
Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network.
METHODS 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 overlayed with patient contacts to imply potential transmission events.
RESULTS RESULTS
Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli); 86% (72/84) harboured an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages showing significant association with patient contacts and movements between four hospital sites and across medical specialities, which was missed on initial investigations.
CONCLUSIONS 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 multi-modal 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.

Identifiants

pubmed: 38245822
pii: 7584711
doi: 10.1093/infdis/jiae019
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Auteurs

Yu Wan (Y)

NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.

Ashleigh C 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.

Adhiratha 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.

Frances Bolt (F)

NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.
Imperial College Healthcare NHS Trust, London, United Kingdom.
Centre for Antimicrobial Optimisation, Hammersmith Hospital, Imperial College London, Du Cane Road, London, United Kingdom.

Alice Ledda (A)

Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom.
HCAI, Fungal, AMR, AMU & Sepsis Division, UK Health Security Agency, London, United Kingdom.

Siddharth Mookerjee (S)

Imperial College Healthcare NHS Trust, London, United Kingdom.

Andrea Y Weiße (AY)

School of Biological Sciences, University of Edinburgh, Scotland, United Kingdom.
School of Informatics, University of Edinburgh, Scotland, United Kingdom.

Maria Getino (M)

NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.

Jane F Turton (JF)

HCAI, Fungal, AMR, AMU & Sepsis Division, UK Health Security Agency, London, United Kingdom.

Hala 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.

Ruta Prakapaite (R)

MRC Centre for Molecular Bacteriology and Infection, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom.

Akshay Sabnis (A)

MRC Centre for Molecular Bacteriology and Infection, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom.

Alireza Abdolrasouli (A)

Imperial College Healthcare NHS Trust, London, United Kingdom.

Kenny 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, United Kingdom.

Luca 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, United Kingdom.

Hugo Donaldson (H)

Department of Microbiology, North West London Pathology, London, United Kingdom.

Mark Gilchrist (M)

NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.
Imperial College Healthcare NHS Trust, London, United Kingdom.

Katie L 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 & Sepsis Division, UK Health Security Agency, London, United Kingdom.

Matthew J 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.

Jonathan A Otter (JA)

NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.

Gerald 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.

Andrew M Edwards (AM)

MRC Centre for Molecular Bacteriology and Infection, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom.

Jesus 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, Du Cane Road, London, United Kingdom.
Centre for Bio-Inspired Technology, Department of Electrical and Electronic Engineering, Faculty of Engineering, Imperial College London, United Kingdom.

Xavier Didelot (X)

School of Life Sciences and Department of Statistics, University of Warwick, United Kingdom.

Mauricio Barahona (M)

Department of Mathematics, Imperial College London, London, United Kingdom.

Alison H Holmes (AH)

NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.
Imperial College Healthcare NHS Trust, London, United Kingdom.
Centre for Antimicrobial Optimisation, Hammersmith Hospital, Imperial College London, Du Cane Road, London, United Kingdom.

Elita 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.

Frances Davies (F)

NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London, United Kingdom.
Imperial College Healthcare NHS Trust, London, United Kingdom.
Department of Microbiology, North West London Pathology, London, United Kingdom.

Classifications MeSH