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

Clin Infect Dis. 2020 Dec 17;71(10):2553-2560. doi: 10.1093/cid/ciz1130.


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.

Keywords: Klebsiella oxytoca; Enterobacterales; GES-5 plasmid; outbreak.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins* / genetics
  • England
  • Humans
  • Klebsiella pneumoniae / genetics
  • Microbial Sensitivity Tests
  • Phylogeny
  • Plasmids / genetics
  • United Kingdom
  • beta-Lactamases* / genetics


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • beta-Lactamases
  • carbapenemase