利奈唑胺和糖肽类抗生素对革兰阳性球菌感染治疗效果的荟萃分析

Linezolid versus glycopeptides for treatment of Gram-positive cocci infections:a meta-analysis of randomised controlled trials

目的对现已发表的利奈唑胺和糖肽类抗生素治疗革兰阳性球菌感染的对照研究文献进行综合分析,比较利奈唑胺和糖肽类抗生素的疗效和安全性。方法计算机检索MEDLINE、EMBASE、OVID、Cochrane library和CNKI等数据库,并追查所有纳入文献的参考文献。纳入英文或中文发表的比较利奈唑胺和糖肽类抗生素治疗革兰阳性球菌感染疗效的随机对照试验,进行荟萃分析。结果共纳入14个随机对照试验,包括6 495例革兰阳性球菌感染患者。荟萃分析结果显示,在临床可评估患者中,治疗结束后利奈唑胺的临床治愈率优于糖肽类抗生素[RR=1.11,95%CI(1.05,1.16),P<0.000 1];在意向性治疗患者中,随访结束后利奈唑胺的临床治愈率亦优于糖肽类抗生素[RR 1.05,95%CI(1.00,1.09),P=0.03]。同时,在微生物学可评估患者中,利奈唑胺治疗患者随访结束后的微生物学总治愈率[RR=1.07,95%CI(1.03,1.12),P=0.000 6]、金黄色葡萄球菌清除率[RR=1.12,95%CI(1.03,1.23),P=0.01]亦优于糖肽类抗生素;而其耐甲氧西林金黄色葡萄球菌清除率[RR=1.10,95%CI(0.99,1.23),P=0.07]与糖肽类抗生素比较无显著差异。另外,利奈唑胺与糖肽类抗生素不良反应总体发生率[RR=1.09,95%CI(0.98,1.21),P=0.10]无显著差异,但利奈唑胺肾功能异常发生率[RR=0.41,95%CI(0.23,0.73),P=0.003]低于糖肽类抗生素,而血小板减少症发生率[RR=9.53,95%CI(3.86,23.56),P<0.000 01]高于糖肽类抗生素。结论利奈唑胺治疗革兰阳性球菌感染的疗效优于糖肽类抗生素,安全性相似,肾毒性较小,但其发生血小板减少症的几率较高,可能限制了其在临床上对难治性革兰阳性球菌感染的长期治疗。

AIM To compare the efficacy and safety of linezolid with glycopeptides in patients with Gram- positive cocci infections by a meta- analysis of randomized controlled trials published in English and Chinese literatures. METHODS The data were collected from the MEDLINE, EMBASE, OVID, the Cochrane library,and CNKI database, and the references of eligible studies were manually screened. Randomized controlled trials published in English and Chinese literatures comparing linezolid with glycopeptides in patients with Gram- positive cocci infections were included and meta-analyzed. RESULTS Fourteen randomized controlled studies comparing linezolid with glycopeptides were analyzed, focusing on 6 495 patients with Gram- positive cocci infections. It was found by meta- analysis that, linezolid was more effective than glycopeptides in clinical treatment success for clinically evaluation patients at the end-of-treatment visit （RR = 1.11, 95%CI （1.05, 1.16）, P 〈 0.000 1）, and it was more effective than glycopeptides for intention-to-treat patients at the test-of- cure visit （RR = 1.05, 95%CI （1.00, 1.09）, P = 0.03）. Linezolid was more effective than glycopeptides in microbiological treatment success （RR = 1.07, 95% CI （1.03, 1.12） , P = 0.000 6）, as well as in Staphylococcus aureus eradication （RR = 1.12, 95%CI （1.03, 1.23） , P = 0.01） for microbiologically evaluation patients at the test-of-cure visit, but, there was no difference for methicillin-resistant Staphylococcus aureus eradication （RR = 1.10, 95%CI （0.99, 1.23）, P= 0.07）. Adverse reaction rates （RR = 1.09, 95%CI （0.98, 1.21）, P = 0.10） was similar between the two drugs, but the rate of abnormal renal function （RR = 0.41, 95%CI （0.23, 0.73）, P = 0.003） was lower in patients receiving linezolid, and thrombocytopenia （RR = 9.53, 95%C1 （3.86, 23.56） , P 〈 0.000 01） was recorded more commonly in patients receiving linezolid. CONCLUSION Linezolid is more effective than glycopeptides for treatment of patients with Gram-positive cocci infections with similar safety and less renal toxicity, but the higher probability of thrombocytopenia may limit its use to Gram-positive cocci infections that are difficult to treat with other antibiotics.