高剂量卡泊芬净治疗侵袭性肺曲霉病的疗效与安全性

Efficacy and safety of high-dose caspofungin in the treatment of invasive pulmonary aspergillosis

目的探讨高剂量卡泊芬净(70 mg/d)初始或挽救治疗侵袭性肺曲霉病的临床疗效和安全性。方法回顾性分析复旦大学附属华山医院2014年6月至2017年10月收治的确诊或临床诊断为侵袭性肺曲霉病,且高剂量卡泊芬净疗程≥7 d的患者21例,按照高剂量卡泊芬净应用前的抗真菌治疗情况将其分为初始治疗组和挽救治疗组,收集患者临床资料和实验室检查结果,分析高剂量卡泊芬净临床疗效、不良反应、总有效率和患者1年生存率。采用Kaplan-Meier法比较两组患者的预后情况。结果21例患者中有20例在治疗基础疾病的过程中机会性感染侵袭性肺曲霉病。初始治疗组5例,治疗时间68(62) d,治疗12周时有1例患者完全应答,3例患者部分应答,1例患者稳定应答,总体有效率为4/5。挽救治疗组16例,治疗时间66.50(58) d,治疗12周时1例为完全应答,10例患者为部分应答,3例患者病情稳定,1例因合并肺部细菌感染死亡,1例患者失访,总体有效率为11/16。随访1年,高剂量卡泊芬净初始治疗患者中无患者死亡,1年生存率为5/5;挽救治疗组16例患者中共3例因合并肺部细菌感染死亡,1年生存率为13/16。治疗过程1例患者出现总胆红素升高,考虑为高剂量卡泊芬净可能相关的药物不良反应。结论对于侵袭性肺曲霉病患者,不论是初始治疗还是挽救治疗,高剂量卡泊芬净均有较好的疗效及安全性。

Objective To investigate the clinical efficacy and safety of high-dose caspofungin (70 mg/d) as initial or salvage treatment for invasive pulmonary aspergillosis. Methods Twenty-one patients with proven or probable invasive pulmonary aspergillosis from June 2014 to October 2017 in Huashan Hospital, Fudan University were retrospectively reviewed. According to the anti-fungal treatment before high-dose caspofungin application, patients were divided into initial treatment group and salvage treatment group. Patients′ clinical data and laboratory data were collected. The characteristics, clinical efficacy, adverse reactions, one-year survival rate and the overall effective rate were evaluated. The prognosis of the two groups was compared by Kaplan-Meier analysis. Results Twenty of the 21 patients opportunistic acquired invasive pulmonary aspergillosis during the treatment of underlying diseases. Five patients were initially treated with high-dose caspofungin for 68 (62) days. At week 12, one patient achieved complete response, 3 patients achieved partial response, and the overall effective rate was 80%(4/5). Sixteen patients received caspofungin as salvage therapy for 66.50 (58) days, of which one patient got complete response at week 12, 10 had partial response, and the overall effective rate was 68.75%(11/16). One-year follow-up showed that no patient died in the initial treatment group, and the one-year survival rate was 100%(5/5). In salvage treatment group, 3 patients died of pulmonary bacterial infections and the one-year survival rate was 81.25%(13/16). During treatment, one patient had elevated total bilirubin, which was possibly associated with high-dose caspofungin. Conclusions High-dose caspofungin regimen has good efficacy and safety, both for initial treatment and salvage therapy in patients with invasive pulmonary aspergillosis.