Objective There is poor evidence to determine the superiority of combination regimens versus monotherapy against infections due to carbapenem-resistant (CR) Gram-negative bacteria. In vivo models can simulate the pathophysiology of infections in humans and assess antibiotic efficacy. We aim to investigate in vivo effects of antibiotic combination on mortality and disease burden for infections due to CR Acinetobacter baumannii , Pseudomonas aeruginosa and Enterobacteriaceae and provide an unbiased overview of existing knowledge. The results of the study can help prioritising future research on the most promising therapies against CR bacteria. Methods and analysis This protocol was formulated using the Systematic Review Protocol for Animal Intervention Studies (SYRCLE) Checklist. Publications will be collected from PubMed, Scopus, Embase and Web of Science. Quality checklists adapted by Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies and SYRCLE’s risk of bias tool will be used. If the meta-analysis seems feasible, the ES and the 95% CI will be analysed. The heterogeneity between studies will be assessed by I2 test. Subgroup meta-analysis will be performed when possible to assess the impact of the studies on efficacy of the treatments. Funnel plotting will be used to evaluate the risk of publication bias. Dissemination This systematic review and meta-analysis is part of a wider research collaboration project, the COmbination tHErapy to treat sepsis due to carbapenem-Resistant bacteria in adult and paediatric population: EvideNCE and common practice (COHERENCE) study that includes also the analyses of in vitro and human studies. Data will be presented at international conferences and the results will be published in peer-reviewed journals. PROSPERO registration number CRD42019128104(available at: ).

中文翻译：

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抗生素组合治疗耐碳青霉烯类革兰氏阴性菌的体内研究：系统评价和荟萃分析方案

目的 缺乏证据来确定联合方案与单一疗法相比对碳青霉烯类耐药 (CR) 革兰氏阴性菌感染的优越性。体内模型可以模拟人类感染的病理生理学并评估抗生素疗效。我们旨在研究抗生素组合对 CR 鲍曼不动杆菌、铜绿假单胞菌和肠杆菌科感染的死亡率和疾病负担的体内影响，并提供对现有知识的公正概述。该研究的结果可以帮助优先考虑未来对最有希望的针对 CR 细菌的疗法的研究。方法和分析 该协议是使用动物干预研究系统审查协议 (SYRCLE) 清单制定的。出版物将从 PubMed、Scopus、Embase 和 Web of Science。将使用通过协作方法对来自实验研究的动物数据进行荟萃分析和审查以及 SYRCLE 的偏倚风险工具改编的质量清单。如果荟萃分析似乎可行，将分析 ES 和 95% CI。研究之间的异质性将通过 I2 检验进行评估。将尽可能进行亚组荟萃分析，以评估研究对治疗效果的影响。漏斗图将用于评估发表偏倚的风险。传播 本系统评价和荟萃分析是更广泛的研究合作项目的一部分，即治疗成人和儿童人群中耐碳青霉烯类细菌引起的败血症的联合疗法：证据和常见做法 (COHERENCE) 研究，其中还包括对体外和人体研究。数据将在国际会议上公布，结果将在同行评审期刊上发表。PROSPERO 注册号 CRD42019128104（可在：）。