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Intravenous Therapy for Chronic Pulmonary Aspergillosis: A Systematic Review and Meta‐analysis
Mycoses ( IF 4.1 ) Pub Date : 2020-07-01 , DOI: 10.1111/myc.13131
Felix Bongomin 1 , Lucy Grace Asio 1 , Ronald Olum 2 , David W Denning 3, 4
Affiliation  

Chronic pulmonary aspergillosis (CPA) is a potentially life‐threatening debilitating lung disease necessitating long‐term oral antifungal treatment. However, development of antifungal‐resistant isolates of Aspergillus and major toxicities requiring discontinuation of treatment limits their use. Intravenous (IV) antifungals are an option in this group of patients. We comprehensively evaluate the response rates to IV antifungals in the management of CPA. We searched Medline and Embase databases to select clinical studies providing information about IV amphotericin B or an echinocandin for the treatment of CPA from inception to May 2020. Reviews, single‐case reports and case series reporting <10 patients were excluded. We evaluated 12 eligible studies. A total of 380 patients received amphotericin B (n = 143) or an echinocandin (n = 237) and were included in the meta‐analysis. In a pooled analysis, overall response to IV antifungals was 61% ((95% confidence interval (CI): 52%‐70%; I2 = 73.3%; P < .001), to amphotericin B was 58% (95% CI: 36%‐80%; I2 = 86.6%; P < .001) and to echinocandins was 62% (95% CI: 53%‐72%; I2 = 63.6%; P < .001). Amphotericin B courses were usually doses at slightly <1 mg/Kg (deoxycholate) or 3 mg/Kg (liposomal) for 2‐3 weeks. Micafungin doses varied from 12.5 to 300 mg (frequently, 150 mg) daily for at least 3 weeks, and sometimes much longer. Liposomal amphotericin B was well tolerated, but led to renal function loss in 25% of patients. Adverse events were observed in 5‐35.3% of patients receiving echinocandins, none of which was considered major. Intravenous antifungals have a place in the management of CPA. A head‐to‐head comparison of amphotericin B and echinocandins is lacking, and future studies should look at evaluating short‐ and longer‐term outcomes of these agents.

中文翻译:

慢性肺曲霉病的静脉治疗:系统评价和 Meta 分析

慢性肺曲霉病 (CPA) 是一种可能危及生命的衰弱性肺部疾病,需要长期口服抗真菌治疗。然而,曲霉抗真菌分离株的发展和需要停止治疗的主要毒性限制了它们的使用。静脉 (IV) 抗真菌药是这组患者的一种选择。我们全面评估了 CPA 管理中对静脉注射抗真菌药的反应率。我们搜索了 Medline 和 Embase 数据库,以选择提供有关从开始到 2020 年 5 月静脉注射两性霉素 B 或棘白菌素治疗 CPA 的信息的临床研究。排除了<10 名患者的综述、单例报告和病例系列报告。我们评估了 12 项符合条件的研究。共有 380 名患者接受了两性霉素 B(n = 143)或棘白菌素(n = 237),并被纳入荟萃分析。在一项汇总分析中,对 IV 抗真菌药的总体反应为 61%((95% 置信区间 (CI):52%-70%;I2 = 73.3%;P < .001),对两性霉素 B 的总体反应为 58%(95% CI) : 36%‐80%; I2 = 86.6%; P < .001) 和棘白菌素为 62% (95% CI: 53%‐72%; I2 = 63.6%; P < .001). 两性霉素 B 疗程通常是剂量略低于 1 mg/Kg(脱氧胆酸盐)或 3 mg/Kg(脂质体),持续 2-3 周。米卡芬净的剂量从每天 12.5 到 300 mg(通常为 150 mg)不等,持续至少 3 周,有时甚至更长. 脂质体两性霉素 B 耐受性良好,但导致 25% 的患者肾功能丧失。5-35.3% 的接受棘白菌素治疗的患者观察到不良事件,没有一个被认为是严重的。静脉注射抗真菌药在 CPA 的管理中占有一席之地。缺乏两性霉素 B 和棘白菌素的直接比较,未来的研究应着眼于评估这些药物的短期和长期结果。
更新日期:2020-07-01
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