Chen Ken, Wang Qi, Pleasants Roy A, Ge Long, Liu Wei, Peng Kangning, Zhai Suodi
Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, China.
Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
BMC Infect Dis. 2017 Feb 20;17(1):159. doi: 10.1186/s12879-017-2263-6.
The most optimal antifungal agent for empiric treatment of invasive fungal diseases (IFDs) in febrile neutropenia is controversial. Our objective was evaluate the relative efficacy of antifungals for all-cause mortality, fungal infection-related mortality and treatment response in this population.
Pubmed, Embase and Cochrane Library were searched to identify randomized controlled trials (RCTs). Two reviewers performed the quality assessment and extracted data independently. Pairwise meta-analysis and network meta-analysis were conducted to compare the antifungals.
Seventeen RCTs involving 4583 patients were included. Risk of bias of included studies was moderate. Pairwise meta-analysis indicated the treatment response rate of itraconazole was significantly better than conventional amphotericin B (RR = 1.33, 95%CI 1.10-1.61). Network meta-analysis showed that amphotericin B lipid complex, conventional amphotericin B, liposomal amphotericin B, itraconazole and voriconazole had a significantly lower rate of fungal infection-related mortality than no antifungal treatment. Other differences in outcomes among antifungals were not statistically significant. From the rank probability plot, caspofungin appeared to be the most effective agent for all-cause mortality and fungal infection-related mortality, whereas micafungin tended to be superior for treatment response. The results were stable after excluding RCTs with high risk of bias, whereas micafungin had the lowest fungal infection-related mortality.
Our results highlighted the necessity of empiric antifungal treatment and indicates that echinocandins appeared to be the most effective agents for empiric treatment of febrile neutropenic patients based on mortality and treatment response. However, more studies are needed to determine the best antifungal agent for empiric treatment. Our systematic review has been prospectively registered in PROSPERO and the registration number was CRD42015026629.
用于发热性中性粒细胞减少症患者侵袭性真菌病（IFD）经验性治疗的最佳抗真菌药物存在争议。我们的目的是评估抗真菌药物在该人群中对全因死亡率、真菌感染相关死亡率及治疗反应的相对疗效。
检索Pubmed、Embase和Cochrane图书馆以识别随机对照试验（RCT）。两名评价者独立进行质量评估并提取数据。进行成对荟萃分析和网状荟萃分析以比较抗真菌药物。
纳入了17项涉及4583例患者的RCT。纳入研究的偏倚风险为中度。成对荟萃分析表明，伊曲康唑的治疗反应率显著优于传统两性霉素B（RR = 1.33，95%CI 1.10 - 1.61）。网状荟萃分析显示，两性霉素B脂质体、传统两性霉素B、两性霉素B脂质复合物、伊曲康唑和伏立康唑的真菌感染相关死亡率显著低于未进行抗真菌治疗。抗真菌药物之间其他结局差异无统计学意义。从排序概率图来看，卡泊芬净似乎是全因死亡率和真菌感染相关死亡率方面最有效的药物，而米卡芬净在治疗反应方面往往更具优势。排除具有高偏倚风险的RCT后结果稳定，而米卡芬净的真菌感染相关死亡率最低。
我们的结果突出了经验性抗真菌治疗的必要性，并表明基于死亡率和治疗反应，棘白菌素似乎是发热性中性粒细胞减少症患者经验性治疗最有效的药物。然而，需要更多研究来确定经验性治疗的最佳抗真菌药物。我们的系统评价已在PROSPERO中进行前瞻性注册，注册号为CRD42015026629。
