Martin, J;
Phan, HTT;
Findlay, J;
Stoesser, N;
Pankhurst, L;
Navickaite, I;
De Maio, N;
... Wilcox, MH; + view all
(2017)
Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission.
Journal of Antimicrobial Chemotherapy
, 72
(11)
pp. 3025-3034.
10.1093/jac/dkx264.
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Abstract
Background: Carbapenemase-producing Enterobacteriaceae (CPE), including KPC-producing Klebsiella pneumoniae (KPC -Kpn ), are an increasing threat to patient safety. Objectives: To use WGS to investigate the extent and complexity of carbapenemase gene dissemination in a controlled KPC outbreak. Materials and methods: Enterobacteriaceae with reduced ertapenem susceptibility recovered from rectal screening swabs/clinical samples, during a 3 month KPC outbreak (2013-14), were investigated for carbapenemase production, antimicrobial susceptibility, variable-number-tandem-repeat profile and WGS [short-read (Illumina), long-read (MinION)]. Short-read sequences were used for MLST and plasmid/Tn 4401 fingerprinting, and long-read sequence assemblies for plasmid identification. Phylogenetic analysis used IQTree followed by ClonalFrameML, and outbreak transmission dynamics were inferred using SCOTTI. Results: Twenty patients harboured KPC-positive isolates (6 infected, 14 colonized), and 23 distinct KPC-producing Enterobacteriaceae were identified. Four distinct KPC plasmids were characterized but of 20 KPC -Kpn (from six STs), 17 isolates shared a single pKpQIL-D2 KPC plasmid. All isolates had an identical transposon (Tn 4401 a), except one KPC -Kpn (ST661) with a single nucleotide variant. A sporadic case of KPC -Kpn (ST491) with Tn 4401 a-carrying pKpQIL-D2 plasmid was identified 10 months before the outbreak. This plasmid was later seen in two other species and other KPC -Kpn (ST14,ST661) including clonal spread of KPC- Kpn (ST661) from a symptomatic case to nine ward contacts. Conclusions: WGS of outbreak KPC isolates demonstrated bla KPC dissemination via horizontal transposition (Tn 4401 a), plasmid spread (pKpQIL-D2) and clonal spread ( K. pneumoniae ST661). Despite rapid outbreak control, considerable dissemination of bla KPC still occurred among K. pneumoniae and other Enterobacteriaceae, emphasizing its high transmission potential and the need for enhanced control efforts.
| Type: | Article |
|---|---|
| Title: | Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/jac/dkx264 |
| Publisher version: | http://doi.org/10.1093/jac/dkx264 |
| Language: | English |
| Additional information: | Copyright © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | plasmids, disease outbreaks, enterobacteriaceae, genome, klebsiella pneumoniae, genetics, microbial colonization, bacterial carbapenemase resistance (bla(kpc)) gene |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1561520 |
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