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Emergence and clonal spread of colistin resistance due to multiple mutational mechanisms in carbapenemase-producing Klebsiella pneumoniae in London

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Title: Emergence and clonal spread of colistin resistance due to multiple mutational mechanisms in carbapenemase-producing Klebsiella pneumoniae in London
Authors: Otter, JA
Doumith, M
Davies, F
Mookerjee, S
Dyakova, E
Gilchrist, M
Brannigan, E
Bamford, K
Galletly, T
Donaldson, H
Aanensen, D
Ellington, M
Hill, R
Turton, J
Hopkins, K
Woodford, N
Holmes, AH
Item Type: Journal Article
Abstract: Carbapenemase-producing Enterobacteriaceae (CPE) are emerging worldwide, limiting therapeutic options. Mutational and plasmid-mediated mechanisms of colistin resistance have both been reported. The emergence and clonal spread of colistin resistance was analysed in 40 epidemiologically-related NDM-1 carbapenemase producing Klebsiella pneumoniae isolates identified during an outbreak in a group of London hospitals. Isolates from July 2014 to October 2015 were tested for colistin susceptibility using agar dilution, and characterised by whole genome sequencing (WGS). Colistin resistance was detected in 25/38 (65.8%) cases for which colistin susceptibility was tested. WGS found that three potential mechanisms of colistin resistance had emerged separately, two due to different mutations in mgrB, and one due to a mutation in phoQ, with onward transmission of two distinct colistin-resistant variants, resulting in two sub-clones associated with transmission at separate hospitals. A high rate of colistin resistance (66%) emerged over a 10 month period. WGS demonstrated that mutational colistin resistance emerged three times during the outbreak, with transmission of two colistin-resistant variants.
Issue Date: 5-Oct-2017
Date of Acceptance: 13-Sep-2017
URI: http://hdl.handle.net/10044/1/50770
DOI: https://dx.doi.org/10.1038/s41598-017-12637-4
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 7
Copyright Statement: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2017
Sponsor/Funder: National Institute for Health Research
National Institute for Health Research
Funder's Grant Number: HPRU-2012-10047
Publication Status: Published
Article Number: 12711
Appears in Collections:Department of Medicine (up to 2019)