利奈唑胺和万古霉素对皮肤及软组织感染治疗效果的Meta分析

Linezolid versus vancomycin in the treatment of skin and soft tissue infections:meta-analysis of randomised controlled trials

目的采用Meta分析方法对现已发表的利奈唑胺和万古霉素治疗革兰阳性球菌皮肤及软组织感染的文献进行综合分析,评价利奈唑胺的疗效及安全性是否优于万古霉素。方法计算机检索Medline数据库、Embase数据库、Ovid数据库、Cochrane图书馆及中文生物医学期刊数据库等网络资源,并查阅所有纳入文献的参考文献,进行Meta分析。纳入用英文或中文发表的比较利奈唑胺和万古霉素治疗革兰阳性球菌皮肤及软组织感染疗效的随机对照试验。由两名评价员独立筛查文献,评价质量和提取资料。采用Jadad量表及随机分配方案隐藏方法评估纳入试验的方法学质量。采用2检验鉴定研究间异质性,使用随机效应或固定效应模型合并研究。采用敏感性分析方法探讨试验结果的影响因素。结果共纳入6个随机对照试验,包括1656例革兰阳性球菌皮肤及软组织感染患者。Meta分析结果显示,在临床可评估患者中,利奈唑胺组治疗结束后[OR 3.78,95%CI(1.18,12.08),P=0.02]及随访结束后[OR 2.15,95%CI(1.46,3.17),P=0.0001]的临床治愈率优于万古霉素组,而在意向性治疗患者中,利奈唑胺组随访结束后[OR 1.37,95%CI(0.98,1.92),P=0.07]的临床治愈率相当于万古霉素;同时,在微生物学可评估患者中,其随访结束后的微生物学总治愈率[OR 2.32,95%CI(1.42,3.79),P=0.0008]、金葡菌清除率[OR=2.73,95%CI(1.82,4.09),P<0.00001]、MRSA清除率[OR=4.00,95%CI(2.31,6.93),P<0.00001]方面,利奈唑胺组亦优于万古霉素组,而在链球菌清除率[OR=1.17,95%CI(0.23,5.97),P=0.85]及肠球菌清除率[OR=6.43,95%CI(0.23,181.82),P=0.28]方面,利奈唑胺相当于万古霉素。结论在治疗革兰阳性球菌皮肤及软组织感染中,利奈唑胺疗效优于或相当于万古霉素。但还需要更严格设计的、大样本的随机双盲对照试验来进一步验证和支持。

Objective A meta-analysis of randomized controlled trials on the efficacy and safety in patients with skin and soft tissue infections caused by Gram-positive infections treated with linezolid versus with vancomycin.Methods The data were collected from the Medline database,Embase database,Ovid database,the Cochrane library,and Chinese Biomedical Database,and the references of eligible studies were manually screened.Randomized controlled trials published in the English and Chinese literature comparing linezolid with vancomycin in patients with skin and soft tissue infections caused by Gram-positive infections were eligible for inclusion.Two investigators independently assessed the quality and extracted the data.The methodological quality of trails was assessed by the Jadad-scale plus allocation concealment.Heterogeneity was examined by Chi-square test.Fixed effects model or random effects model were used to pool the data.Sensitivity analyses were used in the treatment course.Results Six randomized controlled studies comparing linezolid with vancomycin were analyzed,focusing on the 1656 patients with skin and soft tissue infections caused by Gram-positive infections.It was found by meta-analysis that,with respect to clinical treatment success,linezolid was more effective than vancomycin in clinically evaluation patients at the end-of-treatment visit[OR 3.78,95% CI（1.18,12.08）,P=0.02]and at the test-of-cure visit[OR 2.15,95% CI（1.46,3.17）,P=0.0001],however,there was no difference in intention-to-treat patients at the test-of-cure visit[OR 1.37,95% CI（0.98,1.92）,P=0.07].With respect to microbiological treatment success,linezolid was more effective than vancomycin in microbiologically evaluation patients at the test-of-cure visit[OR 2.32,95% CI（1.42,3.79）,P=0.0008].Additionally,empirical treatment with linezolid was associated with increased eradication rates for S.aureus strains[OR=2.73,95% CI（1.82,4.09）,P0.00001]and MRSA strains[OR=4.00,95% CI（2.31,6.93）,P0.00001] in comparison with vancomycin in microbiologically evaluation patients at the test-of-cure visit,but there was no difference in eradication rates for streptococcal species [OR=1.17,95% CI（0.23,5.97）,P=0.85] and enterococcal species [OR=6.43,95% CI（0.23,181.82）,P=0.28].Conclusion Linezolid is more effective than vancomycin or equal to vancomycin for treatment of patients with skin and soft tissue infections caused by Gram-positive infections although rigorously designed large sample size randomized double blind clinical trials are required to further demonstrate and support the conclusion.