A multispecies cluster of GES-5 carbapenemase–producing enterobacterales linked by a geographically disseminated plasmid

Matthew Ellington*, Frances Davies, Elita Jauneikaite, Katie L. Hopkins, Jane Turton, George Adams, Jiri Pavlu, Andrew J. Innes, Christopher Eades, Eimear T. Brannigan, Jacqueline Findlay, Leila White, Frances Bolt, Tokozani Kadhani, Yimmy Chow, Bharat Patel, Siddharth Mookerjee, Jonathan A. Otter, Shiranee Sriskandan, Neil WoodfordAlison Holmes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)2553-2560
Number of pages8
JournalClinical Infectious Diseases
Volume71
Issue number10
DOIs
Publication statusPublished - 15 Nov 2020

Bibliographical note

Publisher Copyright:
© The Author(s) 2019.

Keywords

  • Enterobacterales
  • GES-5 plasmid
  • Klebsiella oxytoca
  • Outbreak

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