McCool Rachael, Gould Ian M, Eales Jacqui, Barata Teresa, Arber Mick, Fleetwood Kelly, Glanville Julie, Kauf Teresa L
York Health Economics Consortium, Enterprise House, Innovation Way, University of York, Heslington, York, YO10 5NQ, UK.
Aberdeen Royal Infirmary, Foresterhill Road, Aberdeen, AB25 2ZN, UK.
BMC Infect Dis. 2017 Jan 7;17(1):39. doi: 10.1186/s12879-016-2100-3.
Tedizolid, the active moiety of tedizolid phosphate, is approved in the United States, the European Union, Canada and a number of other countries for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This network meta-analysis (NMA) evaluates the comparative effectiveness of tedizolid and other antibacterials indicated for the treatment of ABSSSI caused by MRSA.
Systematic review of 10 databases was undertaken to inform an NMA to estimate the relative effectiveness of tedizolid and established monotherapy comparators (ceftaroline, daptomycin, linezolid, teicoplanin, tigecycline, vancomycin) for treating MRSA-associated ABSSSI. Randomized controlled trials enrolling adults with ABSSSI or complicated skin and skin structure infections caused by suspected/documented MRSA were eligible for inclusion. Networks were developed based on similarity of study design, patient characteristics, outcome measures and available data. Outcomes of interest included clinical response at end of therapy (EOT), post-therapy evaluation (PTE) or test-of-cure assessment and treatment discontinuations resulting from adverse events (AEs). Bayesian NMA was conducted for each outcome using fixed-effects and random effects models.
Literature searches identified 3,618 records; 15 trials met the inclusion criteria and were considered suitable for NMA comparison. In fixed-effects models, tedizolid had higher odds of clinical response at EOT (odds ratio [OR], 1.7; credible interval, 1.0, 3.0) and PTE than vancomycin (OR, 1.6; credible interval, 1.1, 2.5). No differences in odds of clinical response at EOT or PTE were observed between tedizolid and other comparators. There was no evidence of a difference among treatments for discontinuation due to AEs. Results from random effects and fixed-effects models were generally consistent.
Tedizolid was superior to vancomycin for clinical response at EOT and PTE. There was no evidence of a difference between tedizolid and other comparators and no evidence of a difference between tedizolid and all comparators when evaluating discontinuation due to AEs. These findings suggest that tedizolid provides an alternative option for the management of serious skin infections caused by suspected or documented MRSA. This study is subject to the limitations inherent in all NMAs, and the results should be interpreted accordingly.
替加环素（tedizolid）是磷酸替加环素的活性部分，已在美国、欧盟、加拿大及其他一些国家获批，用于治疗由某些易感细菌引起的急性细菌性皮肤及皮肤结构感染（ABSSSI），包括耐甲氧西林金黄色葡萄球菌（MRSA）。这项网状Meta分析（NMA）评估了替加环素与其他用于治疗由MRSA引起的ABSSSI的抗菌药物的相对疗效。
对10个数据库进行系统综述，以告知一项NMA，估计替加环素与已确立的单药治疗对照药物（头孢洛林、达托霉素、利奈唑胺、替考拉宁、替加环素、万古霉素）治疗MRSA相关ABSSSI的相对疗效。纳入由疑似/确诊MRSA引起的ABSSSI或复杂性皮肤及皮肤结构感染的成年患者的随机对照试验。根据研究设计、患者特征、结局指标和可用数据的相似性构建网络。感兴趣的结局包括治疗结束时（EOT）的临床反应、治疗后评估（PTE）或治愈测试评估以及因不良事件（AE）导致的治疗中断。使用固定效应和随机效应模型对每个结局进行贝叶斯NMA。
文献检索共识别出3618条记录；15项试验符合纳入标准，被认为适合进行NMA比较。在固定效应模型中，替加环素在EOT时临床反应的优势比（OR，1.7；可信区间，1.0, 3.0）和PTE方面高于万古霉素（OR，1.6；可信区间，1.1, 2.5）。替加环素与其他对照药物在EOT或PTE时临床反应的优势比未观察到差异。没有证据表明因AE导致的治疗中断在各治疗组之间存在差异。随机效应模型和固定效应模型的结果总体一致。
替加环素在EOT和PTE时的临床反应优于万古霉素。在评估因AE导致的治疗中断时，没有证据表明替加环素与其他对照药物之间存在差异，也没有证据表明替加环素与所有对照药物之间存在差异。这些发现表明，替加环素为疑似或确诊MRSA引起的严重皮肤感染的管理提供了一种替代选择。本研究存在所有NMA固有的局限性，结果应相应地进行解释。
