达托霉素治疗复杂皮肤软组织感染有效性及安全性的meta分析

Efficacy and Safety of Daptomycin in the Treatment of Complex Skin and Soft Tissue Infections: a Meta Analysis

关键词:  达托霉素  皮肤及软组织感染  meta分析

Key words:  daptomycin  skin and soft tissue infections  meta analysis

摘要:

目的 对现已发表的达托霉素和其他对照药物治疗革兰阳性球菌皮肤及软组织感染的文献进行meta分析，评价达托霉素的疗效及安全性是否优于对照药物。方法 计算机检索MEDLINE、EMBASE、Cochrane library、Wanfang和CNKI等数据库，纳入比较达托霉素和其他对照药物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，进行meta分析。由2名评价员独立筛查文献，评价质量和提取资料。采用Jadad量表评估纳入试验的方法学质量。采用χ²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。结果 共纳入7个随机对照试验，包括1 810例革兰阳性球菌皮肤及软组织感染患者。Meta分析结果显示，达托霉素组与对照组比，意向性治疗患者随访完成后的临床治愈率差异无统计学意义[OR=1.04，95% CI（0.84，1.29），Z=0.38，P=0.70]；临床可评估患者随访完成后的临床治愈率差异无统计学意义[OR=0.96，95% CI（0.72，1.28），Z=0.26，P=0.80]；微生物学可评估患者随访完成后的微生物学总治愈率差异无统计学意义[OR=0.96，95% CI（0.70，1.31），Z=0.27，P=0.79]。另外，达托霉素组与对照药物组在不良反应总体发生率方面亦相当[OR=0.89，95% CI（0.69，1.15），Z=0.89，P=0.37]，但达托霉素组患者磷酸肌酸激酶（CPK）升高比例高于对照组，差异有统计学意义[OR=1.95，95% CI（1.04，3.65），Z=0.208，P=0.04]。结论 在治疗革兰阳性球菌皮肤及软组织感染中，达托霉素疗效相当于万古霉素或其他对照药物，药物不良反应中CPK的升高比例显著高于对照组。但还需要设计更严格的、大样本的随机双盲对照试验来进一步验证和支持。

Abstract:

OBJECTIVE A meta analysis of the published literature on the efficacy and safety in patients with skin and soft tissue infections caused by Gram-positive infections treated with daptomycin versus comparator drugs. METHODS Meta analysis was applied to analyse data which were collected from MEDLINE, EMBASE, Cochrane library,Wanfang Data and CNKI. Randomized controlled trials the efficacy of compared daptomycin and the comparator drugs in the patients with skin and soft tissue infections caused by Gram-positive infections were eligible for inclusion. Two investigators independently screened the literature, assessed the quality and extracted the data. The methodological quality of trails was assessed by the Jadad-scale. Chi-square test was employed to examine heterogeneity. Fixed effects model or random effects model were used to pool the data. RESULTS Seven randomized controlled studies comparing daptomycin with the comparator drugs were analyzed, including 1 810 patients with skin and soft tissue infections caused by Gram-positive infections. The results of meta analysis showed that daptomycin compared with the control group, there was no significant difference in clinical cure rate of patients with intention-to-treat treatment after follow-up[OR=1.04, 95%CI(0.84, 1.29), Z=0.38, P=0.70]; there was also no difference in clinically evaluated patients at the test-of-cure visit[OR=0.96, 95%CI(0.72, 1.28), Z=0.26, P=0.80]. With respect to microbiological treatment success, daptomycin had no more effective than the comparator drugs in microbiologically evaluated patients at the test-of-cure visit[OR=0.96, 95%CI(0.70, 1.31), Z=0.27, P=0.79]. Treatment with daptomycin was not associated with more adverse effects comparing with the comparator drugs[OR=0.89, 95%CI(0.69, 1.15), Z=0.89, P=0.37]. However, there was a significant difference in the growth of creatine phosphate kinase(CPK) in daptomycin group[OR=1.95, 95%CI(1.04, 3.65), Z=0.208, P=0.04]. CONCLUSION Daptomycin is equivalent to vancomycin or the other comparator drugs in treatment of patients with skin and soft tissue infections caused by Gram-positive infections, and the growth of CPK is significantly higher than that of control group. Furthermore, rigorous designed large sample size randomized double blind clinical trials are required to demonstrate and support this conclusion.