Choosing Optimal Antifungal Agents To Prevent Fungal Infections in Nonneutropenic Critically Ill Patients: Trial Sequential Analysis, Network Meta-analysis, and Pharmacoeconomic Analysis.
Choosing Optimal Antifungal Agents To Prevent Fungal Infections in Nonneutropenic Critically Ill Patients: Trial Sequential Analysis, Network Meta-analysis, and Pharmacoeconomic Analysis.
复制标题
选择最佳抗真菌药物预防非中性粒细胞减少危重患者的真菌感染：试验序贯分析、网络荟萃分析和药物经济学分析。
DOI：
10.1128/aac.00620-17
复制
发表时间：
2017
影响因子：
4.9
通讯作者：
Dong Yalin
中科院分区：
文献类型：
--
作者：
Wang Yan;Xie Jiao;Xing Yuanming;Chen Lu;Li Ying;Meng Ti;Dong Weihua;Wang Xue;Dong Yalin
在侵袭性真菌感染（IFI）被微生物学证实之前，危重患者的抗真菌干预措施的使用和首选药物仍有争议。我们进行了系统的文献检索，以确定比较非靶向抗真菌治疗应用于非血小板减少性重症患者的随机对照试验（RCT）。主要结果是全因死亡率和经证实的IFI率。随机效应模型与试验序贯分析（TSA）一起使用，进行网络荟萃分析（NMA）以获得间接证据，并从患者的角度在整个生命周期内完成使用决策分析模型的成本效益分析。共纳入了19项RCT，涉及2，556例患者（7项干预）。非靶向抗真菌治疗并没有显著降低全因死亡率的发生率（比值比[OR] = 0.89，95%可信区间[95%CI] = 0.70 - 1.14），但相对于安慰剂/无干预，它确实降低了已证实的IFI的发生率（OR = 0.45，95%CI = 0.29 - 0.71）。TSA表明，有足够的证据支持这些发现。在NMA中，两个主要结局的唯一显著差异是氟康唑和安慰剂/无干预预防已证实的IFI（OR = 0.35，95%CI = 0.19至0.65）。基于中国的药物和住院费用，氟康唑、卡泊芬净和米卡芬净相对于安慰剂/无干预的每生命年节省的增量成本-效果比分别为889美元、9,994美元和10,351美元。非靶向抗真菌治疗显著降低了非血小板减少性重症患者的IFI发生率，但与安慰剂/无干预相比，没有死亡率获益。在耐受性良好的抗真菌药物中，氟康唑仍然是唯一一种有效预防IFI的药物，并且比棘白菌素便宜得多。
The use of antifungal interventions in critically ill patients prior to invasive fungal infection (IFI) being microbiologically confirmed and the preferred drug are still controversial. A systematic literature search was performed to identify randomized controlled trials (RCTs) that compared untargeted antifungal treatments applied to nonneutropenic critically ill patients. The primary outcomes were all-cause mortality and proven IFI rates. A random-effects model was used with trial sequential analyses (TSA), a network meta-analysis (NMA) was conducted to obtain indirect evidence, and a cost-effectiveness analysis using a decision-analytic model was completed from the patient perspective over a lifetime horizon. In total, 19 RCTs involving 2,556 patients (7 interventions) were included. Untargeted antifungal treatment did not significantly decrease the incidence of all-cause mortality (odds ratio [OR] = 0.89, 95% confidence interval [95%CI] = 0.70 to 1.14), but it did reduce the incidence of proven IFI (OR = 0.45, 95%CI = 0.29 to 0.71) relative to placebo/no intervention. The TSA showed that there was sufficient evidence supporting these findings. In the NMA, the only significant difference found for both primary outcomes was between fluconazole and placebo/no intervention in preventing proven IFI (OR = 0.35, 95%CI = 0.19 to 0.65). Based on drug and hospital costs in China, the incremental cost-effectiveness ratios per life-year saved for fluconazole, caspofungin, and micafungin relative to placebo/no intervention corresponded to US$889, US$9,994, and US$10,351, respectively. Untargeted antifungal treatment significantly reduced proven IFI rates in nonneutropenic critically ill patients but with no mortality benefits relative to placebo/no intervention. Among the well-tolerated antifungals, fluconazole remains the only one that is effective for IFI prevention and significantly cheaper than echinocandins.