A Multispecies Cluster of GES-5 Carbapenemase–Producing Enterobacterales Linked by a Geographically Disseminated Plasmid. (20th November 2019)

• Record Type: Journal Article
• Authors: Ellington, Matthew J; Davies, Frances; Jauneikaite, Elita; Hopkins, Katie L; Turton, Jane F; Adams, George; Pavlu, Jiri; Innes, Andrew J; Eades, Christopher; Brannigan, Eimear T; Findlay, Jacqueline; White, Leila; Bolt, Frances; Kadhani, Tokozani; Chow, Yimmy; Patel, Bharat; Mookerjee, Siddharth; Otter, Jonathan A; Sriskandan, Shiranee; Woodford, Neil; Holmes, Alison
• Is Part Of: Clinical infectious diseases. Volume 71:Number 10(2020)
• Page Start: 2553
• Page End: 2560
• Publication Date: 2019-11-20
• Subjects: GES-5 plasmid -- Enterobacterales -- outbreak -- Klebsiella oxytoca; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciz1130
• Languages: English
• ISSNs: 1058-4838

Abstract

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. Abstract : Whole-genome sequencing informed the detection of active and previously missed hospital clusters of Klebsiella oxytoca with GES-5; modes of spread were reinterpreted and GES-5 plasmid was found to be widely disseminated in other species of bacteria at remote locations.