Journal
CLINICAL INFECTIOUS DISEASES
Volume 71, Issue 10, Pages 2553-2560Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciz1130
Keywords
GES-5 plasmid; Enterobacterales; outbreak; Klebsiella oxytoca
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Funding
- NIHR HPRU in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London
- PHE
- Sanger Institute
- University of Cambridge Veterinary School
- Imperial College Health Partners
- NIHR Imperial Biomedical Research Centre
- Rosetrees Trust [M683]
- Stoneygate Trust [M683]
- MRC [MR/T005254/1, MR/R015600/1] Funding Source: UKRI
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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 colt, 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.
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