Thom H, Thompson J C, Scott D A, Halfpenny N, Sulham K, Corey G R
a a School of Social and Community Medicine, University of Bristol , Bristol , UK.
Curr Med Res Opin. 2015 Aug;31(8):1539-51. doi: 10.1185/03007995.2015.1058248. Epub 2015 Jun 30.
The objective was to conduct a systematic review and network meta-analysis (NMA) of existing treatments for ABSSSI focusing on the novel lipoglycopeptide oritavancin.
EMBASE, MEDLINE, MEDLINE in Process, CENTRAL (Cochrane), and select conferences were searched for randomized controlled trials investigating antimicrobial agents for the treatment of ABSSSI. NMA was used to estimate the odds ratios of the Test-Of-Cure (TOC) and Early Clinical Response (ECR) outcomes for treatments relative to vancomycin in the ITT populations. Sub-group analyses in MRSA and MSSA populations were conducted for TOC; sensitivity analyses investigated the use of the clinically evaluable (CE) populations and the restriction to trials following the recent FDA guidelines for clinical trials.
The systematic review identified 52 trials. The most commonly investigated treatments were vancomycin and linezolid; most trials reported TOC, but not ECR. The posterior mean and 95% credible intervals for odds ratios of TOC for antimicrobial agents relative to vancomycin were: linezolid (1.55; 0.91-2.57), daptomycin (2.18; 0.90-5.42), and oritavancin 1200 mg (1.06; 0.80-1.43). The odds ratio of ECR for oritavancin 1200 mg was 1.02 (0.23-4.33). In the MRSA sub-group the odds ratios relative to vancomycin for TOC were: linezolid (1.55; 0.96-2.46), daptomycin (0.74; 0.13-3.66), and oritavancin 1200 mg (0.94; 0.44-2.02). In the MSSA sub-group they were linezolid (1.36; 0.15-13.34) and oritavancin 1200 mg (0.82; 0.08-7.83). These results were robust to the sensitivity analyses.
This NMA provides a unified framework for the comparison of all available antimicrobial agents used in the treatment of ABSSSI and is the first to assess the ECR end-point. The results suggest equivalence of clinical efficacy between vancomycin, daptomycin, linezolid, and novel antimicrobial agents including oritavancin for the treatment of ABSSSI at TOC. The wide uncertainty margins indicate the heterogeneity of the available evidence and the need for further research.
进行一项系统评价和网状Meta分析（NMA），聚焦新型脂糖肽奥利万星，评估现有治疗急性细菌性皮肤和皮肤结构感染（ABSSSI）的方法。
检索EMBASE、MEDLINE、MEDLINE在研数据库、Cochrane中心对照试验注册库（CENTRAL）以及部分会议，查找关于抗菌药物治疗ABSSSI的随机对照试验。使用NMA估计ITT人群中各治疗方法相对于万古霉素的治疗结束时治愈率（TOC）和早期临床反应（ECR）结局的比值比。对MRSA和MSSA人群的TOC进行亚组分析；敏感性分析探讨了临床可评估（CE）人群的使用情况以及按照美国食品药品监督管理局（FDA）近期临床试验指南对试验进行限制的情况。
系统评价共纳入52项试验。研究最频繁的治疗方法是万古霉素和利奈唑胺；大多数试验报告了TOC，但未报告ECR。抗菌药物相对于万古霉素的TOC比值比的后验均值及95%可信区间为：利奈唑胺（1.55；0.91 - 2.57）、达托霉素（2.18；0.90 - 5.42）、1200mg奥利万星（1.06；0.80 - 1.43）。1200mg奥利万星的ECR比值比为1.02（0.23 - 4.33）。在MRSA亚组中，相对于万古霉素的TOC比值比为：利奈唑胺（1.55；0.96 - 2.46）、达托霉素（0.74；0.13 - 3.66）、1200mg奥利万星（0.94；0.44 - 2.02）。在MSSA亚组中，比值比为利奈唑胺（1.36；0.15 - 13.34）、1200mg奥利万星（0.82；0.08 - 7.83）。这些结果在敏感性分析中具有稳健性。
本NMA为比较所有用于治疗ABSSSI的现有抗菌药物提供了一个统一框架，且首次评估了ECR终点。结果表明，在治疗结束时治愈率方面，万古霉素、达托霉素、利奈唑胺以及包括奥利万星在内的新型抗菌药物在治疗ABSSSI时临床疗效相当。较宽的不确定性区间表明现有证据存在异质性，需要进一步研究。
