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

Jonathan A. Otter, Michel Doumith, Frances Davies, Siddharth Mookerjee, Eleonora Dyakova, Mark Gilchrist, Eimear T. Brannigan, Kathleen Bamford, Tracey Galletly, Hugo Donaldson, David M. Aanensen, Matthew Ellington, Robert Hill, Jane Turton, Katie L. Hopkins, Neil Woodford, Alison Holmes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


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.

Original languageEnglish
Article number12711
JournalScientific Reports
Issue number1
Publication statusPublished - 1 Dec 2017

Bibliographical note

Funding Information:
We wish to acknowledge several colleagues from Imperial College Healthcare NHS Trust for their input (Darren Parsons, Manfred Almeida, Sweenie Goonesekera and Monica Rebec), and colleagues from Public Health England (Yimmy Chow, Isidro Carrion, Bharat Patel) and the AMRHAI Reference Unit for their support. The research was partially funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London in partnership with Public Health England (PHE). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England. We also acknowledge the support of the Imperial College Healthcare Trust NIHR Biomedical Research Centre (BRC). The researchers are independent from the funders. The funders had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

Publisher Copyright:
© 2017 The Author(s).


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