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A multi-species cluster of GES-5 carbapenemase producing Enterobacterales linked by a geographically disseminated plasmid

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Title: A multi-species cluster of GES-5 carbapenemase producing Enterobacterales linked by a geographically disseminated plasmid
Authors: Ellington, MJ
Davies, F
Jauneikaite, E
Hopkins, KL
Turton, JF
Adams, G
Pavlu, J
Innes, AJ
Eades, C
Brannigan, ET
Findlay, J
White, L
Bolt, F
Kadhani, T
Chow, Y
Patel, B
Mookerjee, S
Otter, JA
Sriskandan, S
Woodford, N
Holmes, A
Item Type: Journal Article
Abstract: 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 GES-5 carbapenemase-positive Klebsiella oxytoca infection was identified by whole genome sequencing (WGS) (later found to be part of a cluster of three 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 MALDI-TOF, antimicrobial susceptibility testing followed EUCAST guidelines. Ertapenem-resistant isolates were referred to Public Health England for characterization using PCR detection of GES, pulse-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 on WGS. 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 two 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,E. coli and E. cloacae isolates from unlinked patients within the same hospital group and in human and wastewater isolates from three hospitals elsewhere in the UK. 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.
Issue Date: 15-Nov-2020
Date of Acceptance: 18-Nov-2019
URI: http://hdl.handle.net/10044/1/76018
DOI: 10.1093/cid/ciz1130
ISSN: 1058-4838
Publisher: Oxford University Press (OUP)
Start Page: 2553
End Page: 2560
Journal / Book Title: Clinical Infectious Diseases
Volume: 71
Issue: 10
Copyright Statement: © 2019 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: National Institute for Health Research
National Institute for Health Research
National Institute for Health Research
Medical Research Council (MRC)
Rosetrees Trust
Funder's Grant Number: NF-SI-0617-10176
Keywords: Klebsiella oxytoca
GES-5 plasmid
Klebsiella oxytoca
GES-5 plasmid
06 Biological Sciences
11 Medical and Health Sciences
Publication Status: Published
Conference Place: United States
Online Publication Date: 2019-11-20
Appears in Collections:Department of Immunology and Inflammation
Department of Infectious Diseases
Faculty of Medicine
School of Public Health