Saag M S, Powderly W G, Cloud G A, Robinson P, Grieco M H, Sharkey P K, Thompson S E, Sugar A M, Tuazon C U, Fisher J F
Department of Medicine, University of Alabama, Birmingham School of Medicine.
N Engl J Med. 1992 Jan 9;326(2):83-9. doi: 10.1056/NEJM199201093260202.
Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS). Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease.
In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patients, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period.
Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P less than 0.0001).
Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined.
静脉注射两性霉素B，无论是否联合氟胞嘧啶，通常是获得性免疫缺陷综合征（AIDS）患者隐球菌性脑膜炎的标准治疗方法。氟康唑，一种口服三唑类药物，是治疗隐球菌病的一种有前景的新方法。
在一项随机多中心试验中，我们比较了静脉注射两性霉素B与口服氟康唑作为AIDS相关急性隐球菌性脑膜炎的初始治疗方法。所有诊断均经培养确诊的符合条件的患者，以2:1的比例随机分配接受氟康唑（每日200mg）或两性霉素B治疗。如果患者在10周治疗期结束时连续两次脑脊液培养阴性，则认为治疗成功。
194例符合条件的患者中，131例接受氟康唑治疗，63例接受两性霉素B治疗（成功治疗患者的平均每日剂量为每公斤体重0.4mg，治疗失败患者为每公斤体重0.5mg；P = 0.34）。63例接受两性霉素B治疗的患者中有25例治疗成功（40%；95%置信区间为26%至53%），131例接受氟康唑治疗的患者中有44例治疗成功（34%；95%置信区间为25%至42%）（P = 0.40）。两组因隐球菌病导致的总体死亡率无显著差异（两性霉素B组与氟康唑组，63例中有9例[14%] vs. 131例中有24例[18%]；P = 0.48）；然而，氟康唑组治疗前两周的死亡率较高（15% vs. 8%；P = 0.2）。两性霉素B组首次脑脊液培养转阴的中位时间为42天（95%置信区间为28至71天），氟康唑组为64天（95%置信区间为53至67天）（P = 0.25）。多因素分析确定精神状态异常（嗜睡、昏睡或迟钝）是治疗期间高死亡风险的最重要预测因素（P < 0.0001）。
氟康唑是AIDS患者隐球菌性脑膜炎初始治疗中两性霉素B的有效替代药物。单药治疗对治疗失败风险低的患者最有效。高风险患者的最佳治疗方案仍有待确定。
