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

• Published in: Clinical infectious diseases Vol. 71; no. 10; pp. 2553 - 2560
• Main 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
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 17.12.2020
• Subjects: Anti-Bacterial Agents - pharmacology; Bacterial Proteins - genetics; beta-Lactamases - genetics; England; Humans; Klebsiella pneumoniae - genetics; Major and Commentaries; Microbial Sensitivity Tests; Phylogeny; Plasmids - genetics; United Kingdom; England; United Kingdom; outbreak; GES-5 plasmid; Enterobacterales; Klebsiella oxytoca
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciz1130

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. 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.