A Multispecies Cluster of GES-5 Carbapenemase-Producing Enterobacterales Linked by a Geographically Disseminated Plasmid.


Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
17 12 2020
Historique:
received: 05 08 2019
accepted: 18 11 2019
pubmed: 21 11 2019
medline: 28 4 2021
entrez: 21 11 2019
Statut: ppublish

Résumé

Early and accurate treatment of infections due to carbapenem-resistant organisms is facilitated by rapid diagnostics, but rare resistance mechanisms can compromise detection. One year after a Guiana Extended-Spectrum (GES)-5 carbapenemase-positive Klebsiella oxytoca infection was identified by whole-genome sequencing (WGS; later found to be part of a cluster of 3 cases), a cluster of 11 patients with GES-5-positive K. oxytoca was identified over 18 weeks in the same hospital. Bacteria were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry, antimicrobial susceptibility testing followed European Committee on Antimicrobial Susceptibility Testing guidelines. Ertapenem-resistant isolates were referred to Public Health England for characterization using polymerase chain reaction (PCR) detection of GES, pulsed-field gel electrophoresis (PFGE), and WGS for the second cluster. The identification of the first GES-5 K. oxytoca isolate was delayed, being identified by WGS. Implementation of a GES-gene PCR informed the occurrence of the second cluster in real time. In contrast to PFGE, WGS phylogenetic analysis refuted an epidemiological link between the 2 clusters; it also suggested a cascade of patient-to-patient transmission in the later cluster. A novel GES-5-encoding plasmid was present in K. oxytoca, Escherichia coli, and Enterobacter cloacae isolates from unlinked patients within the same hospital group and in human and wastewater isolates from 3 hospitals elsewhere in the United Kingdom. Genomic sequencing revolutionized the epidemiological understanding of the clusters; it also underlined the risk of covert plasmid propagation in healthcare settings and revealed the national distribution of the resistance-encoding plasmid. Sequencing results also informed and led to the ongoing use of enhanced diagnostic tests for detecting carbapenemases locally and nationally.

Sections du résumé

BACKGROUND
Early and accurate treatment of infections due to carbapenem-resistant organisms is facilitated by rapid diagnostics, but rare resistance mechanisms can compromise detection. One year after a Guiana Extended-Spectrum (GES)-5 carbapenemase-positive Klebsiella oxytoca infection was identified by whole-genome sequencing (WGS; later found to be part of a cluster of 3 cases), a cluster of 11 patients with GES-5-positive K. oxytoca was identified over 18 weeks in the same hospital.
METHODS
Bacteria were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry, antimicrobial susceptibility testing followed European Committee on Antimicrobial Susceptibility Testing guidelines. Ertapenem-resistant isolates were referred to Public Health England for characterization using polymerase chain reaction (PCR) detection of GES, pulsed-field gel electrophoresis (PFGE), and WGS for the second cluster.
RESULTS
The identification of the first GES-5 K. oxytoca isolate was delayed, being identified by WGS. Implementation of a GES-gene PCR informed the occurrence of the second cluster in real time. In contrast to PFGE, WGS phylogenetic analysis refuted an epidemiological link between the 2 clusters; it also suggested a cascade of patient-to-patient transmission in the later cluster. A novel GES-5-encoding plasmid was present in K. oxytoca, Escherichia coli, and Enterobacter cloacae isolates from unlinked patients within the same hospital group and in human and wastewater isolates from 3 hospitals elsewhere in the United Kingdom.
CONCLUSIONS
Genomic sequencing revolutionized the epidemiological understanding of the clusters; it also underlined the risk of covert plasmid propagation in healthcare settings and revealed the national distribution of the resistance-encoding plasmid. Sequencing results also informed and led to the ongoing use of enhanced diagnostic tests for detecting carbapenemases locally and nationally.

Identifiants

pubmed: 31746994
pii: 5634258
doi: 10.1093/cid/ciz1130
pmc: PMC7744980
doi:

Substances chimiques

Anti-Bacterial Agents 0
Bacterial Proteins 0
beta-Lactamases EC 3.5.2.6
carbapenemase EC 3.5.2.6

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2553-2560

Subventions

Organisme : Medical Research Council
ID : MR/R015600/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T005254/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

Auteurs

Matthew J Ellington (MJ)

National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infections Service, Public Health England, London, United Kingdom.

Frances Davies (F)

Imperial College Healthcare National Health Service Trust, London, United Kingdom.

Elita Jauneikaite (E)

National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom.

Katie L Hopkins (KL)

National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infections Service, Public Health England, London, United Kingdom.

Jane F Turton (JF)

Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infections Service, Public Health England, London, United Kingdom.

George Adams (G)

Imperial College Healthcare National Health Service Trust, London, United Kingdom.

Jiri Pavlu (J)

Imperial College Healthcare National Health Service Trust, London, United Kingdom.

Andrew J Innes (AJ)

Imperial College Healthcare National Health Service Trust, London, United Kingdom.

Christopher Eades (C)

Imperial College Healthcare National Health Service Trust, London, United Kingdom.

Eimear T Brannigan (ET)

Imperial College Healthcare National Health Service Trust, London, United Kingdom.

Jacqueline Findlay (J)

Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infections Service, Public Health England, London, United Kingdom.

Leila White (L)

Microbiology, Royal Preston Hospital, Lancashire Teaching Hospitals National Health Service Foundation Trust, Preston, United Kingdom.

Frances Bolt (F)

Imperial College Healthcare National Health Service Trust, London, United Kingdom.

Tokozani Kadhani (T)

Imperial College Healthcare National Health Service Trust, London, United Kingdom.

Yimmy Chow (Y)

North West London Health Protection Team, Public Health England, London, United Kingdom.

Bharat Patel (B)

Public Health Laboratory London, National Infections Service, Public Health England, London, United Kingdom.

Siddharth Mookerjee (S)

Imperial College Healthcare National Health Service Trust, London, United Kingdom.

Jonathan A Otter (JA)

National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Imperial College Healthcare National Health Service Trust, London, United Kingdom.

Shiranee Sriskandan (S)

National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.

Neil Woodford (N)

National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infections Service, Public Health England, London, United Kingdom.

Alison Holmes (A)

National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Imperial College Healthcare National Health Service Trust, London, United Kingdom.

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Classifications MeSH