Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections.Report as inadecuate




Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections. - Download this document for free, or read online. Document in PDF available to download.

Reference: Thompson, CN, Thieu, NT, Vinh, PV et al., (2015). Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections. The Journal of Antimicrobial Chemotherapy, 71 (3), 807-815.Citable link to this page:

 

Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections.

Abstract: ObjectivesWe aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally.MethodsClinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis. Time–kill experiments were performed to evaluate the impact of MIC on thein vitro growth of Shigella and Cox regression modelling was used to compare clinical outcome between treatments and Shigella species. ResultsShigella flexneri patients treated with gatifloxacin had significantly worse outcomes than those treated with ciprofloxacin. However, the MICs of fluoroquinolones were not significantly associated with poorer outcome. The presence of S83L and A87T mutations in thegyrAgene significantly increased MICs of fluoroquinolones. Finally, elevated MICs and the presence of theqnrSgene allowedShigellato replicate efficiently in vitro in high concentrations of ciprofloxacin.ConclusionsWe found that below the CLSI breakpoint, there was no association between MIC and clinical outcome in paediatric shigellosis infections. However, S. flexneri patients had worse clinical outcomes when treated with gatifloxacin in this study regardless of MIC. Additionally, Shigella harbouring the qnrS gene are able to replicate efficiently in high concentrations of ciprofloxacin and we hypothesize that such strains possess a competitive advantage against fluoroquinolone-susceptible strains due to enhanced shedding and transmission.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Wellcome Trust   Funder: Royal Society   Notes:© The Authors 2015. 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

Bibliographic Details

Publisher: Oxford University Press

Publisher Website: http://www.oxfordjournals.org/

Journal: The Journal of Antimicrobial Chemotherapysee more from them

Publication Website: http://jac.oxfordjournals.org/

Issue Date: 2015-12

pages:807-815Identifiers

Urn: uuid:4b845c4a-21af-4fe1-84f5-5488d02b6a37

Source identifier: 588181

Eissn: 1460-2091

Doi: https://doi.org/10.1093/jac/dkv400

Issn: 0305-7453 Item Description

Type: Journal article;

Language: eng

Version: Publisher's version Tiny URL: pubs:588181

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Author: Thompson, CN - institutionUniversity of Oxford Oxford, MSD, NDM, Tropical Medicine - - - Thieu, NT - - - Vinh, PV - - - Duc, AN -

Source: https://ora.ox.ac.uk/objects/uuid:4b845c4a-21af-4fe1-84f5-5488d02b6a37



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