London School of Hygiene & Tropical Medicine, Keppel Street, Bloomsbury, London, WC1E 7HT, UK.
Helse Nord Tuberculosis Initiative, University of Malawi College of Medicine, Blantyre, Malawi.
Syst Rev. 2018 Dec 23;7(1):246. doi: 10.1186/s13643-018-0917-0.
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.
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.
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.
PROSPERO CRD42018089275.
抗菌药物耐药性造成了巨大的健康和经济负担，并有潜力成为全球主要死因，但导致其产生的根本因素尚未得到充分描述。微生物暴露于抗菌药物后，随后产生或选择耐药性的情况，以及加剧微生物和人为因素的情况，都有明确的记录。然而，这种风险的性质和程度，以及它如何因抗菌药物类别和治疗持续时间而异，尚未得到明确界定。我们系统综述和网络荟萃分析的目标是确定抗菌药物暴露时间与耐药性选择之间的关系。我们将使用大环内酯类作为研究的抗菌药物类别，并以肺炎链球菌携带作为指示生物。我们的次要结局包括症状持续时间、治疗失败和复发风险以及耐药机制的描述。
我们将进行系统综述，如果研究报告了任何年龄组患者使用大环内酯类药物治疗任何适应证与耐药性肺炎链球菌发生率之间的关系，则选择发表的随机对照试验（RCT）纳入研究。我们将使用预先确定的搜索策略在 MEDLINE、Embase、全球卫生和 Cochrane 对照试验中心注册库中识别符合这些纳入标准的研究。两名作者将独立筛选标题和摘要、审查全文并进行数据提取。我们将使用 Cochrane 协作组织的工具评估纳入 RCT 的质量。如果可行，我们将进行两两荟萃分析模型，以确定大环内酯类药物治疗时间与大环内酯类耐药肺炎链球菌之间的关系。如果确定的研究符合网络荟萃分析（NMA）的假设，我们将使用间接比较进一步对该关系进行建模。我们的方案利用系统评价和荟萃分析（PRISMA）和方案扩展（PRISMA-P）以及网络荟萃分析（PRISMA 对 NMA）的首选报告项目的报告指南。我们的综述也将按照这些标准进行报告。
确定抗菌药物暴露时间与耐药性产生或选择之间的关系，将为抗菌药物处方设计、治疗指南以及医生和患者的行为提供信息。因此，这项工作将是对抗菌药物耐药性管理策略的全面实现的有力贡献。
PROSPERO CRD42018089275。
