Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial
Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial
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DOI：
10.1016/s0140-6736(04)16301-0
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发表时间：
2004-05-29
期刊：
影响因子：
168.9
通讯作者：
Harrison, TS
中科院分区：
文献类型：
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作者：
Brouwer, AE;Rajanuwong, A;Harrison, TS
背景隐球菌性脑膜炎的药物治疗通常需要2周以上的时间来消毒脑脊液（CSF）。体外和动物研究支持使用阿替霉素B、氟胞嘧啶和氟康唑联合治疗隐球菌病。我们比较了这些药物的组合对隐球菌脑膜炎患者的初始治疗的杀真菌活性。方法64例首次发病的HIV相关隐球菌脑膜炎患者随机接受以下初始治疗：（每日0.7 mg/kg）;阿替霉素B+氟胞嘧啶（每日100 mg/kg）;阿替霉素B加氟康唑（每日400 mg）;或阿替霉素B、氟胞嘧啶和氟康唑的三联疗法。我们的主要终点是杀真菌活性，测量的CSF隐球菌菌落形成单位（CFU）的减少率从系列定量CSF培养在第3，7，和14天的treatment.Findings基线CSF CFU计数是一个重要的预后因素。隐球菌从CSF中的清除呈指数级，并且与单用阿替霉素B（p=0.0006）、阿替霉素B加氟康唑（p=0.02）或三联疗法（p=0.02）相比，阿替霉素B加氟胞嘧啶显著更快。脑脊液培养的定量为准确评估新型隐球菌脑膜炎治疗方案的杀真菌活性提供了一种强有力的新方法。
Background It frequently takes more than 2 weeks for drug treatments for cryptococcal meningitis to sterilise cerebrospinal fluid (CSF). In-vitro and animal studies lend support to the use of combinations of amphotericin B, flucytosine, and fluconazole for treatment of cryptococcosis. We compared the fungicidal activity of combinations of these drugs for initial treatment of patients with cryptococcal meningitis.Methods 64 patients with a first episode of HIV-associated cryptococcal meningitis were randomised to initial treatment with: amphotericin B (0.7 mg/kg daily); amphotericin B plus flucytosine (100 mg/kg daily); amphotericin B plus fluconazole (400 mg daily); or triple therapy with amphotericin B, flucytosine, and fluconazole. Our primary endpoint was fungicidal activity, measured by the rate of reduction in CSF cryptococcal colony-forming units (CFU) from serial quantitative CSF cultures on days 3, 7, and 14 of treatment.Findings Baseline CSF CFU counts were an important prognostic factor. Clearance of cryptococci from the CSF was exponential and was significantly faster with amphotericin B plus flucytosine than with amphotericin B alone (p=0.0006), amphotericin B plus fluconazole (p=0.02), or triple therapy (p=0.02).Interpretation At these doses, amphotericin B plus flucytosine is the most rapidly fungicidal regimen. Quantification of CSF cultures provides a powerful new means to accurately assess the fungicidal activity of new treatment regimens for cryptococcal meningitis.