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dc.contributor.authorDivala, Titus H.
dc.contributor.authorCorbett, Elizabeth L.
dc.contributor.authorStagg, Helen R.
dc.contributor.authorNliwasa, Marriott
dc.contributor.authorSloan, Derek J.
dc.contributor.authorFrench, Neil
dc.contributor.authorFielding, Katherine L.
dc.identifier.citationDivala , T H , Corbett , E L , Stagg , H R , Nliwasa , M , Sloan , D J , French , N & Fielding , K L 2018 , ' Effect of the duration of antimicrobial exposure on the development of antimicrobial resistance (AMR) for macrolide antibiotics : protocol for a systematic review with a network meta-analysis ' , Systematic Reviews , vol. 7 , 246 .
dc.identifier.otherPURE: 257273149
dc.identifier.otherPURE UUID: 5a3a5ccd-e7a6-4692-9c34-d6b36d4b2907
dc.identifier.otherRIS: urn:3DBC4DA88446D1A9E6D90209C5B86666
dc.identifier.otherScopus: 85058911560
dc.identifier.otherWOS: 000454269000004
dc.descriptionTHD is funded by the Commonwealth Scholarship Commission and the Helse Nord RHF. This review is part of his PhD work at LSHTM. ELC is funded by a Wellcome Trust Senior Research Fellowship in Clinical Science: WT200901. HRS is supported by the Medical Research Council [MR/R008345/1].en
dc.description.abstractBackground: Antimicrobial resistance generates a huge health and economic burden and has the potential to become the leading cause of death globally, but its underlying drivers are yet to be fully described. The association between a microbe’s exposure to antimicrobials and subsequent development of, or selection for, resistance is well documented, as are the exacerbating microbial and human factors. However, the nature and extent of this risk, and how it varies by antimicrobial class and duration of treatment, is poorly defined. The goal of our systematic review and network meta-analysis is to determine the relationship between the duration of antimicrobial exposure and selection for resistance. We will use macrolides as the antimicrobial class of interest and Streptococcus pneumoniae carriage as an indicator organism. Our secondary outcomes include duration of symptoms, risk of treatment failure and recurrence, and descriptions of resistance mechanisms. Methods:  We will conduct a systematic review, selecting studies if they are published randomised controlled trials (RCTs) which report the relationship between taking a macrolide for any indication and incidence of resistant Streptococcus pneumoniae in patients of any age group. We will use a predefined search strategy to identify studies meeting these eligibility criteria in MEDLINE, Embase, Global Health and the Cochrane Central Register of RCTs. Two authors will independently screen titles and abstracts, review the full texts and undertake data extraction. We will use the Cochrane Collaboration’s tool to assess the quality of included RCTs. If feasible, we will perform pair-wise meta-analysis modelling to determine the relationship between the duration of macrolide treatment and development of macrolide resistant Streptococcus pneumoniae. If the identified studies meet the assumptions for a network meta-analysis (NMA), we will additionally model this relationship using indirect comparisons. Our protocol utilises reporting guidance by Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the extensions for protocols (PRISMA-P) and network meta-analyses (PRISMA for NMA). Our review will also report to these standards. Discussion:  Establishing the relationship between the duration of antimicrobial exposure and development of, or selection for, resistance will inform the design of antimicrobial prescriptions, treatment guidelines and the behaviour of both physicians and patients. This work will therefore be a strong contribution towards the full realisation of current antimicrobial resistance stewardship strategies.
dc.relation.ispartofSystematic Reviewsen
dc.rights© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.en
dc.subjectAntimicrobial resistanceen
dc.subjectNetwork meta-analysisen
dc.subjectStreptococcus pneumoniaeen
dc.subjectTreatment durationen
dc.subjectTreatment failureen
dc.subjectDisease recurrenceen
dc.subjectResistance mechanismsen
dc.subjectRA0421 Public health. Hygiene. Preventive Medicineen
dc.titleEffect of the duration of antimicrobial exposure on the development of antimicrobial resistance (AMR) for macrolide antibiotics : protocol for a systematic review with a network meta-analysisen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Infection and Global Health Divisionen
dc.description.statusPeer revieweden

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