氟胞嘧啶或氟康唑与两性霉素B联合治疗隐球菌性脑膜炎的疗效和安全性的系统评价

Efficacy and safety of flucytosine or fluconazole combined with amphotericin B for the treatment of cryptococcal meningitis:A systematic review and meta-analysis

目的:系统评价氟胞嘧啶(5FC)或氟康唑(FCZ)与两性霉素B(AMB)联合治疗隐球菌性脑膜炎(CM)的疗效和安全性,以期为临床治疗提供循证参考。方法:计算机检索中国知网、中文科技期刊数据库、万方数据库、PubMed、Embase、Web of Science以及Cochrane Library,收集关于AMB+5FC与AMB+FCZ对比治疗CM的疗效和安全性的文献研究,提取数据资料并进行质量评价后,采用RevMan 5.1及STATA 12.0统计软件进行Meta分析。结果:共纳入6篇中英文文献,7项研究,483例患者。Meta分析结果显示,有效性方面,AMB+5FC组的2周死亡率低于AMB+FCZ组[OR=1.88,95%CI(1.09,3.23),P=0.02],但在10周死亡率方面2组对比无显著性差异[OR=1.29,95%CI(0.83,2.03),P=0.26];安全性方面,两组在不良反应(AEs)发生率方面无显著性差异[OR=0.91,95%CI(0.73,1.12),P=0.36]。结论:Meta分析结果显示,早期应用AMB+5FC可以降低CM患者的死亡率,虽然两组AEs发生率无显著性差异,但AMB+5FC可能发生更严重的AEs。

OBJECTIVE To evaluate the efficacy and safety of flucytosine or fluconazole combined with amphotericin B for the treatment of cryptococcal meningitis (CM), then provide the evidence-based reference for clinical practice. METHODS Clinical trials comparing AMB+5FC with AMB+FCZ for the treatment of CM published in CNKI, VIP, WANFANG, PubMed, EMbase, Web of Science, and Cochrane library were searched, then abstracted data and appraised the methodological quality for each included study. Statistical analysis was performed using the RevMan 5.1 and STATA 12.0 software. RESULTS Six Chinese and English articles were included, involving seven studies and 483 patients. For the efficacy, this meta-analysis revealed that the mortality rate by week 2 was lower for AMB+5FC than for AMB+FCZ[OR=1.88, 95% CI (1.09,3.23),P=0.02]; however, there was no statistically significant difference in the mortality rate by week 10 between these two groups[OR=1.29, 95% CI (0.83, 2.03), P=0.26]. For the safety, this meta-analysis revealed that there was no significant difference in the rate of adverse effects (AEs) between two groups[OR=0.91, 95% CI (0.73, 1.12), P=0.36]. CONCLUSION This meta-analysis reveals that administration of AMB+5FC at early stage can reduce the mortality rate in patients with CM, though there is no significant difference in the rate of AEs between two groups. AMB+5FC possibly associates with more seriously AEs.