低剂量两性霉素B联合氟胞嘧啶治疗隐球菌脑膜炎的临床分析

Evaluation of low-dose amphotericin B and flucytosine in the treatment of cryptococcal meningitis

目的探讨采用低剂量两性霉素B联合氟胞嘧啶治疗非获得性免疫缺陷综合征（AIDS）相关隐球菌脑膜炎（隐脑）的临床疗效及安全性。方法回顾性分析复旦大学附属华山医院1998年1月至2007年12月间，低剂量两性霉素B（〈0．7mg·kg^-1·d^-1）联合氟胞嘧啶治疗非AIDS相关隐脑1周以上、资料完整的31例病例，总结其临床特征，分析其临床疗效、药物不良反应及预后转归。结果31例患者中，8例患者合并基础疾病，确诊时最常见的临床表现为头痛、发热、脑膜刺激征、呕吐，22例（78．6％）患者的颅脑MRI或CT检查发现异常。应用低剂量两性霉素B联合氟胞嘧啶治疗后，完全应答率19．4％（6／31），部分应答率54．8％（17／31），总有效率74．2％。除1例失访外，其余患者随访1年的归因病死率及全因病死率分别为0（0／30）和10．0％（3／30）。此外，26例（83．9％）患者出现两性霉素B相关不良反应，以肝肾功能损害、心律失常、贫血为多见，但大部分不良反应均可耐受。结论低剂量两性霉素B联合氟胞嘧啶治疗非AIDS相关隐脑，有较好的疗效和安全性。

Objective To evaluate the efficacy and safety of low-dose amphotericin B （ 〈 0. 7 mg · kg^-1 · d^-1） and flucytosine in patients with non-AIDS-associated cryptococcal meningitis. Methods In non-AIDS patients with cryptococcal meningitis admitted to Huashan Hospital, Fudan University in Shanghai from January 1998 to December 2007, 31 were initially treated with low-dose amphotericin B and flucytosine for more than 1 week. The clinical characteristics, clinical responses, drug-related adverse reactions and outcome of these patients were retrospectively evaluated. Results Among the 31 patients enrolled in this study, 8 patients had one or more predisposing factors. Headache, fever, meningeal irritation and vomiting were common clinical symptoms and signs when cryptococcal meningitis was diagnosed. The result of cranial CT scan and/or MRI showed abnormality in 22 cases （78. 6% ）. When the therapy of low-dose amphotericin B and flucytosine ended, the complete response rate was 19. 4% （6/31 ） , partial response rate was 54. 8% （ 17/31 ）, and total effective rate was 74. 2%. Except for 1 patient lost to follow-up, the 1-year attributable and all-canse mortality among the remaining 30 patients were 0 （0/30） and 10. 0% （3/30） respectively. On the other hand, 26 （83.9%） patients had amphotericin B-related adverse reactions, including renal impairment, liver injury, arrhythmia, and anemia, etc. However, most of these reactions were tolerable. Conclusion Low-dose amphotericin B and flucytosine can be used in non-AIDS-associated cryptococcal meningitis with both acceptable efficacy and safety.