Veterans Affairs San Diego Healthcare System; UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences, 3350 La Jolla Village Drive (119-E), San Diego, CA 92161, USA.
Curr Med Res Opin. 2010 Feb;26(2):407-21. doi: 10.1185/03007990903454912.
To evaluate the clinical and microbiological outcomes of linezolid versus vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infection (cSSTI) using a meta-analysis.
Clinical trials were identified using PubMed, the Cochrane Central Register of Controlled Trials, and the International Pharmaceutical Abstracts from inception to March 2009. Primary outcomes evaluated resolution of signs and symptoms of infection in clinically evaluable (CE) patients, and microbiological eradication in both the modified intent-to-treat (MITT) and MRSA evaluable (MRSA ME) patients. MITT patients had a culture-confirmed Gram-positive pathogen (S. aureus) at baseline. Secondary outcomes included mortality, adverse drug reactions (ADR), and discontinuation due to ADRs. The Mantel-Haenszel odds ratios (OR) with 95% confidence intervals (CI) were calculated using the fixed effects model based on the assumption that there was little to no heterogeneity between the studies in the primary analysis. Sensitivity analyses were performed for each outcome by removing the most weighted study.
Five studies with a total of 2652 patients (1361/linezolid; 1291/vancomycin) were identified. Resolution of infection in CE patients (OR = 1.41; 95% CI: 1.03, 1.95) and MITT patients (OR = 1.91; 95% CI: 1.33, 2.76) favored the use of linezolid over vancomycin, but did not remain significant after sensitivity analyses (CE: OR = 1.29; 95% CI: 0.81, 2.05; MITT: OR = 1.73; 95% CI: 0.87, 3.41). Microbiological eradication in MRSA ME patients consistently favored the use of linezolid over vancomycin (OR = 2.90; 95% CI: 1.90, 4.41). No difference in mortality was observed between the two groups (OR = 1.17; 95% CI: 0.85, 1.62). Higher proportions of linezolid patients were found to have diarrhea (119/1361 vs. 52/1291), nausea (102/1361 vs. 46/1291) and thrombocytopenia (54/1121 vs. 8/1071), whereas a higher proportion of vancomycin patients were found to have renal insufficiency compared to linezolid (16/634 vs. 4/703). Inconsistent results were seen with the incidence of anemia and rash between the base-case (anemia: OR = 1.36; 95% CI: 0.90, 2.08; rash: OR = 0.26; 95% CI: 0.10, 0.68) and sensitivity analyses (anemia: OR = 2.33; 95% CI: 1.24, 4.37; rash: OR = 0.57; 95% CI: 0.12, 2.71). Discontinuation due to ADRs was not statistically different between linezolid and vancomycin (OR = 1.06; 95% CI: 0.75, 1.51).
Resolution of infection in CE and MITT patients were inconsistent; however, a sub-analysis revealed that linezolid was more likely to consistently achieve microbiologic eradication in MRSA ME patients. Apparent risks of thrombocytopenia, nausea, diarrhea, and possibly anemia may limit linezolid use in treating MRSA cSSTI. This study was limited due to an inability to assess for the effects of hetero-resistance and appropriate vancomycin dosing on outcomes. Moreover, the small number of studies made controlling for heterogeneity challenging.
采用荟萃分析评估利奈唑胺与万古霉素治疗耐甲氧西林金黄色葡萄球菌（MRSA）复杂性皮肤和软组织感染（cSSTI）的临床和微生物学疗效。
通过 PubMed、Cochrane 对照试验中心注册库和国际药学文摘，从创建至 2009 年 3 月检索临床试验。主要疗效终点为临床可评估（CE）患者感染体征和症状的缓解情况，以及改良意向治疗（MITT）和 MRSA 可评估（MRSA ME）患者的微生物学清除率。MITT 患者基线时培养确认革兰阳性病原体（金黄色葡萄球菌）。次要疗效终点包括死亡率、药物不良反应（ADR）和因 ADR 而停药。采用固定效应模型计算基于假设研究间异质性较小或不存在的 Mantel-Haenszel 比值比（OR）。采用逐一排除最具权重的研究进行敏感性分析。
共纳入 5 项研究，总计 2652 例患者（利奈唑胺组 1361 例，万古霉素组 1291 例）。CE 患者（OR=1.41；95%CI：1.03，1.95）和 MITT 患者（OR=1.91；95%CI：1.33，2.76）的感染缓解情况，以及 MRSA ME 患者的微生物学清除率均倾向于利奈唑胺，但在敏感性分析后不再具有统计学意义（CE：OR=1.29；95%CI：0.81，2.05；MITT：OR=1.73；95%CI：0.87，3.41）。MRSA ME 患者中，利奈唑胺的微生物学清除率始终优于万古霉素（OR=2.90；95%CI：1.90，4.41）。两组死亡率无差异（OR=1.17；95%CI：0.85，1.62）。利奈唑胺组腹泻（119/1361 例 vs. 52/1291 例）、恶心（102/1361 例 vs. 46/1291 例）和血小板减少症（54/1121 例 vs. 8/1071 例）的发生率高于万古霉素组，而万古霉素组肾功能不全的发生率高于利奈唑胺组（16/634 例 vs. 4/703 例）。基于基础病例（贫血：OR=1.36；95%CI：0.90，2.08；皮疹：OR=0.26；95%CI：0.10，0.68）和敏感性分析（贫血：OR=2.33；95%CI：1.24，4.37；皮疹：OR=0.57；95%CI：0.12，2.71），贫血和皮疹的发生率不一致。利奈唑胺与万古霉素组因 ADR 停药的比例无统计学差异（OR=1.06；95%CI：0.75，1.51）。
CE 和 MITT 患者的感染缓解情况不一致；然而，亚组分析显示利奈唑胺更有可能持续实现 MRSA ME 患者的微生物学清除率。血小板减少症、恶心、腹泻和可能的贫血风险可能限制利奈唑胺治疗 MRSA cSSTI 的应用。本研究由于无法评估异质性耐药和适当的万古霉素剂量对结果的影响而受到限制。此外，研究数量较少，使得控制异质性具有挑战性。
