Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS. A randomized trial

OBJECTIVE: To compare the efficacy of fluconazole with amphotericin B plus flucytosine in the treatment of cryptococcal meningitis. DESIGN: Patients were randomly assigned to oral fluconazole, 400 mg/d, for 10 weeks or to amphotericin B, 0.7 mg/kg body weight daily for 1 week, then three times weekly for 9 weeks combined with flucytosine, 150 mg/kg d, in four divided doses. SETTING: Los Angeles County-University of Southern California Medical Center. PATIENTS: Between 15 February and 7 December 1988, 42 patients had evidence of their first episode of cryptococcal meningitis, of whom 21 participated in the trial. All patients enrolled were men with the acquired immunodeficiency syndrome (AIDS) except one woman who was receiving prednisone therapy and was excluded from the final analysis. RESULTS: Of 14 patients with AIDS assigned to fluconazole, 8 (57%; 95% CI, 29% to 82%) failed; none of the 6 patients with AIDS failed who were assigned to amphotericin B plus flucytosine therapy (0%; CI, 0% to 46%) (Fisher exact test, P = 0.04). The mean duration of positive cerebrospinal fluid cultures was 40.6 +/- 5.4 days in patients receiving fluconazole and 15.6 +/- 6.6 days in patients receiving amphotericin B plus flucytosine (Mann-Whitney test, P = 0.02). Overall, 4 patients assigned to fluconazole therapy died whereas no patient assigned to amphotericin B plus flucytosine therapy died (Fisher exact test, P = 0.27). CONCLUSION: Amphotericin B used in combination with flucytosine has superior mycologic and clinical efficacy compared with fluconazole for the treatment of cryptococcal meningitis in patients with AIDS.     

氟康唑治疗隐球菌脑膜炎24例临床分析

目的 探讨氟康唑单用或联合氟胞嘧啶治疗非AIDS相关隐球菌脑膜炎(隐脑)的临床特征、疗效及转归.方法 回顾性分析复旦大学附属华山医院1997年至2007年间24例非AIDS相关隐脑病例(初始治疗均为氟康唑单用或联合氟胞嘧啶),观察其临床特点、疗效及转归.采用算术平均数和中位数进行统计学分析.结果 氟康唑治疗中位剂量为400 mg/d,中位疗程为20.5 d.初始治疗2周时,部分应答4例,占16.7%.无应答20例,占83.3%,有效率为16.7%,无死亡病例.治疗10周时,部分应答8例,占33.3%,完全应答7例,占29.2%,无应答4例,占16.7%,有效率为62.5%,死亡5例,占20.8%.病程中22例因疗效不佳而加用或改用两性霉索B、两性霉素B脂质分散体或伊曲康唑等.随访1年,24例中有11例死亡,其中8例死于隐脑,3例死于其他疾病.结论 对于非AIDS相关隐脑,以氟康唑单用或联合氟胞嘧啶作为初始治疗者疗效不佳,大部分息者因治疗失败而需改用其他抗真菌药物治疗,提示该方案不适用于非AIDS相关隐脑的初始治疗.     

氟康唑治疗隐球菌脑膜炎24例临床分析

目的 探讨氟康唑单用或联合氟胞嘧啶治疗非AIDS相关隐球菌脑膜炎(隐脑)的临床特征、疗效及转归.方法 回顾性分析复旦大学附属华山医院1997年至2007年间24例非AIDS相关隐脑病例(初始治疗均为氟康唑单用或联合氟胞嘧啶),观察其临床特点、疗效及转归.采用算术平均数和中位数进行统计学分析.结果 氟康唑治疗中位剂量为400 mg/d,中位疗程为20.5 d.初始治疗2周时,部分应答4例,占16.7%.无应答20例,占83.3%,有效率为16.7%,无死亡病例.治疗10周时,部分应答8例,占33.3%,完全应答7例,占29.2%,无应答4例,占16.7%,有效率为62.5%,死亡5例,占20.8%.病程中22例因疗效不佳而加用或改用两性霉索B、两性霉素B脂质分散体或伊曲康唑等.随访1年,24例中有11例死亡,其中8例死于隐脑,3例死于其他疾病.结论 对于非AIDS相关隐脑,以氟康唑单用或联合氟胞嘧啶作为初始治疗者疗效不佳,大部分息者因治疗失败而需改用其他抗真菌药物治疗,提示该方案不适用于非AIDS相关隐脑的初始治疗.     

氟康唑治疗隐球菌脑膜炎24例临床分析

目的 探讨氟康唑单用或联合氟胞嘧啶治疗非AIDS相关隐球菌脑膜炎(隐脑)的临床特征、疗效及转归.方法 回顾性分析复旦大学附属华山医院1997年至2007年间24例非AIDS相关隐脑病例(初始治疗均为氟康唑单用或联合氟胞嘧啶),观察其临床特点、疗效及转归.采用算术平均数和中位数进行统计学分析.结果 氟康唑治疗中位剂量为400 mg/d,中位疗程为20.5 d.初始治疗2周时,部分应答4例,占16.7%.无应答20例,占83.3%,有效率为16.7%,无死亡病例.治疗10周时,部分应答8例,占33.3%,完全应答7例,占29.2%,无应答4例,占16.7%,有效率为62.5%,死亡5例,占20.8%.病程中22例因疗效不佳而加用或改用两性霉索B、两性霉素B脂质分散体或伊曲康唑等.随访1年,24例中有11例死亡,其中8例死于隐脑,3例死于其他疾病.结论 对于非AIDS相关隐脑,以氟康唑单用或联合氟胞嘧啶作为初始治疗者疗效不佳,大部分息者因治疗失败而需改用其他抗真菌药物治疗,提示该方案不适用于非AIDS相关隐脑的初始治疗.     

氟康唑治疗隐球菌脑膜炎24例临床分析

目的 探讨氟康唑单用或联合氟胞嘧啶治疗非AIDS相关隐球菌脑膜炎(隐脑)的临床特征、疗效及转归.方法 回顾性分析复旦大学附属华山医院1997年至2007年间24例非AIDS相关隐脑病例(初始治疗均为氟康唑单用或联合氟胞嘧啶),观察其临床特点、疗效及转归.采用算术平均数和中位数进行统计学分析.结果 氟康唑治疗中位剂量为400 mg/d,中位疗程为20.5 d.初始治疗2周时,部分应答4例,占16.7%.无应答20例,占83.3%,有效率为16.7%,无死亡病例.治疗10周时,部分应答8例,占33.3%,完全应答7例,占29.2%,无应答4例,占16.7%,有效率为62.5%,死亡5例,占20.8%.病程中22例因疗效不佳而加用或改用两性霉索B、两性霉素B脂质分散体或伊曲康唑等.随访1年,24例中有11例死亡,其中8例死于隐脑,3例死于其他疾病.结论 对于非AIDS相关隐脑,以氟康唑单用或联合氟胞嘧啶作为初始治疗者疗效不佳,大部分息者因治疗失败而需改用其他抗真菌药物治疗,提示该方案不适用于非AIDS相关隐脑的初始治疗.     

氟康唑治疗隐球菌脑膜炎24例临床分析

目的 探讨氟康唑单用或联合氟胞嘧啶治疗非AIDS相关隐球菌脑膜炎(隐脑)的临床特征、疗效及转归.方法 回顾性分析复旦大学附属华山医院1997年至2007年间24例非AIDS相关隐脑病例(初始治疗均为氟康唑单用或联合氟胞嘧啶),观察其临床特点、疗效及转归.采用算术平均数和中位数进行统计学分析.结果 氟康唑治疗中位剂量为400 mg/d,中位疗程为20.5 d.初始治疗2周时,部分应答4例,占16.7%.无应答20例,占83.3%,有效率为16.7%,无死亡病例.治疗10周时,部分应答8例,占33.3%,完全应答7例,占29.2%,无应答4例,占16.7%,有效率为62.5%,死亡5例,占20.8%.病程中22例因疗效不佳而加用或改用两性霉索B、两性霉素B脂质分散体或伊曲康唑等.随访1年,24例中有11例死亡,其中8例死于隐脑,3例死于其他疾病.结论 对于非AIDS相关隐脑,以氟康唑单用或联合氟胞嘧啶作为初始治疗者疗效不佳,大部分息者因治疗失败而需改用其他抗真菌药物治疗,提示该方案不适用于非AIDS相关隐脑的初始治疗.     

氟康唑治疗隐球菌脑膜炎24例临床分析

目的 探讨氟康唑单用或联合氟胞嘧啶治疗非AIDS相关隐球菌脑膜炎(隐脑)的临床特征、疗效及转归.方法 回顾性分析复旦大学附属华山医院1997年至2007年间24例非AIDS相关隐脑病例(初始治疗均为氟康唑单用或联合氟胞嘧啶),观察其临床特点、疗效及转归.采用算术平均数和中位数进行统计学分析.结果 氟康唑治疗中位剂量为400 mg/d,中位疗程为20.5 d.初始治疗2周时,部分应答4例,占16.7%.无应答20例,占83.3%,有效率为16.7%,无死亡病例.治疗10周时,部分应答8例,占33.3%,完全应答7例,占29.2%,无应答4例,占16.7%,有效率为62.5%,死亡5例,占20.8%.病程中22例因疗效不佳而加用或改用两性霉索B、两性霉素B脂质分散体或伊曲康唑等.随访1年,24例中有11例死亡,其中8例死于隐脑,3例死于其他疾病.结论 对于非AIDS相关隐脑,以氟康唑单用或联合氟胞嘧啶作为初始治疗者疗效不佳,大部分息者因治疗失败而需改用其他抗真菌药物治疗,提示该方案不适用于非AIDS相关隐脑的初始治疗.     

氟康唑治疗隐球菌脑膜炎24例临床分析

目的 探讨氟康唑单用或联合氟胞嘧啶治疗非AIDS相关隐球菌脑膜炎(隐脑)的临床特征、疗效及转归.方法 回顾性分析复旦大学附属华山医院1997年至2007年间24例非AIDS相关隐脑病例(初始治疗均为氟康唑单用或联合氟胞嘧啶),观察其临床特点、疗效及转归.采用算术平均数和中位数进行统计学分析.结果 氟康唑治疗中位剂量为400 mg/d,中位疗程为20.5 d.初始治疗2周时,部分应答4例,占16.7%.无应答20例,占83.3%,有效率为16.7%,无死亡病例.治疗10周时,部分应答8例,占33.3%,完全应答7例,占29.2%,无应答4例,占16.7%,有效率为62.5%,死亡5例,占20.8%.病程中22例因疗效不佳而加用或改用两性霉索B、两性霉素B脂质分散体或伊曲康唑等.随访1年,24例中有11例死亡,其中8例死于隐脑,3例死于其他疾病.结论 对于非AIDS相关隐脑,以氟康唑单用或联合氟胞嘧啶作为初始治疗者疗效不佳,大部分息者因治疗失败而需改用其他抗真菌药物治疗,提示该方案不适用于非AIDS相关隐脑的初始治疗.     

氟康唑治疗隐球菌脑膜炎24例临床分析

目的 探讨氟康唑单用或联合氟胞嘧啶治疗非AIDS相关隐球菌脑膜炎(隐脑)的临床特征、疗效及转归.方法 回顾性分析复旦大学附属华山医院1997年至2007年间24例非AIDS相关隐脑病例(初始治疗均为氟康唑单用或联合氟胞嘧啶),观察其临床特点、疗效及转归.采用算术平均数和中位数进行统计学分析.结果 氟康唑治疗中位剂量为400 mg/d,中位疗程为20.5 d.初始治疗2周时,部分应答4例,占16.7%.无应答20例,占83.3%,有效率为16.7%,无死亡病例.治疗10周时,部分应答8例,占33.3%,完全应答7例,占29.2%,无应答4例,占16.7%,有效率为62.5%,死亡5例,占20.8%.病程中22例因疗效不佳而加用或改用两性霉索B、两性霉素B脂质分散体或伊曲康唑等.随访1年,24例中有11例死亡,其中8例死于隐脑,3例死于其他疾病.结论 对于非AIDS相关隐脑,以氟康唑单用或联合氟胞嘧啶作为初始治疗者疗效不佳,大部分息者因治疗失败而需改用其他抗真菌药物治疗,提示该方案不适用于非AIDS相关隐脑的初始治疗.     

氟康唑治疗隐球菌脑膜炎24例临床分析

目的 探讨氟康唑单用或联合氟胞嘧啶治疗非AIDS相关隐球菌脑膜炎(隐脑)的临床特征、疗效及转归.方法 回顾性分析复旦大学附属华山医院1997年至2007年间24例非AIDS相关隐脑病例(初始治疗均为氟康唑单用或联合氟胞嘧啶),观察其临床特点、疗效及转归.采用算术平均数和中位数进行统计学分析.结果 氟康唑治疗中位剂量为400 mg/d,中位疗程为20.5 d.初始治疗2周时,部分应答4例,占16.7%.无应答20例,占83.3%,有效率为16.7%,无死亡病例.治疗10周时,部分应答8例,占33.3%,完全应答7例,占29.2%,无应答4例,占16.7%,有效率为62.5%,死亡5例,占20.8%.病程中22例因疗效不佳而加用或改用两性霉索B、两性霉素B脂质分散体或伊曲康唑等.随访1年,24例中有11例死亡,其中8例死于隐脑,3例死于其他疾病.结论 对于非AIDS相关隐脑,以氟康唑单用或联合氟胞嘧啶作为初始治疗者疗效不佳,大部分息者因治疗失败而需改用其他抗真菌药物治疗,提示该方案不适用于非AIDS相关隐脑的初始治疗.     

氟康唑治疗隐球菌脑膜炎24例临床分析

目的 探讨氟康唑单用或联合氟胞嘧啶治疗非AIDS相关隐球菌脑膜炎(隐脑)的临床特征、疗效及转归.方法 回顾性分析复旦大学附属华山医院1997年至2007年间24例非AIDS相关隐脑病例(初始治疗均为氟康唑单用或联合氟胞嘧啶),观察其临床特点、疗效及转归.采用算术平均数和中位数进行统计学分析.结果 氟康唑治疗中位剂量为400 mg/d,中位疗程为20.5 d.初始治疗2周时,部分应答4例,占16.7%.无应答20例,占83.3%,有效率为16.7%,无死亡病例.治疗10周时,部分应答8例,占33.3%,完全应答7例,占29.2%,无应答4例,占16.7%,有效率为62.5%,死亡5例,占20.8%.病程中22例因疗效不佳而加用或改用两性霉索B、两性霉素B脂质分散体或伊曲康唑等.随访1年,24例中有11例死亡,其中8例死于隐脑,3例死于其他疾病.结论 对于非AIDS相关隐脑,以氟康唑单用或联合氟胞嘧啶作为初始治疗者疗效不佳,大部分息者因治疗失败而需改用其他抗真菌药物治疗,提示该方案不适用于非AIDS相关隐脑的初始治疗.     

氟康唑治疗隐球菌脑膜炎24例临床分析

目的 探讨氟康唑单用或联合氟胞嘧啶治疗非AIDS相关隐球菌脑膜炎(隐脑)的临床特征、疗效及转归.方法 回顾性分析复旦大学附属华山医院1997年至2007年间24例非AIDS相关隐脑病例(初始治疗均为氟康唑单用或联合氟胞嘧啶),观察其临床特点、疗效及转归.采用算术平均数和中位数进行统计学分析.结果 氟康唑治疗中位剂量为400 mg/d,中位疗程为20.5 d.初始治疗2周时,部分应答4例,占16.7%.无应答20例,占83.3%,有效率为16.7%,无死亡病例.治疗10周时,部分应答8例,占33.3%,完全应答7例,占29.2%,无应答4例,占16.7%,有效率为62.5%,死亡5例,占20.8%.病程中22例因疗效不佳而加用或改用两性霉索B、两性霉素B脂质分散体或伊曲康唑等.随访1年,24例中有11例死亡,其中8例死于隐脑,3例死于其他疾病.结论 对于非AIDS相关隐脑,以氟康唑单用或联合氟胞嘧啶作为初始治疗者疗效不佳,大部分息者因治疗失败而需改用其他抗真菌药物治疗,提示该方案不适用于非AIDS相关隐脑的初始治疗.     

Cryptococcal Meningitis: Current Approaches to Management in Patients With and Without AIDS

Cryptococcal meningitis is a life-threatening fungal infection of the central nervous system (CNS). Its management is characterized by the administration of initial combination antifungal therapy by following the principles of induction, consolidation, and maintenance therapy with aggressive management of elevated intracranial pressure (ICP). These tenets apply to patients with and without AIDS. Recent prospective trials on combination antifungal therapy, and the timing of the initiation of highly active antiretroviral therapy (HAART), suggest amphotericin B plus flucytosine and initiation of HAART are optimal therapy for management of patients with AIDS and cryptococcal meningitis. The paucity of prospective data on the management of cryptococcal meningitis in patients without AIDS is the most challenging aspect of formulating treatment guidelines, but the principles of induction, consolidation, and maintenance still apply. Combination antifungal therapy with a lipid formulation of amphotericin B plus flucytosine is generally indicated for this group, especially for those with a predisposition to renal dysfunction. Future research targeting this population may further inform recommendations.     

隐球菌性脑膜炎26例临床分析

目的 总结隐球菌性脑膜炎的资料,提高对隐球菌性脑膜炎的认识。方法 回顾性总结近20年（1981年10月至2001年9月）隐球菌性脑膜炎的一般资料,诊断及治疗情况。结果 共26例患者,其中男12例,女14例,年龄5－62岁,平均35．6岁,有基础疾病者16例,其中系统红斑狼疮（SLE）9例,人类免疫缺陷病毒感染或艾滋病（HIV／AIDS）4例,其他疾病3例;有明确鸽子接触史者12例;误诊结核性脑膜炎者5例,狼疮脑病者6例;墨汁染色找到隐球菌者23例（23／26）,乳胶凝集试验抗原阳性20例（20／20）。颅内压明显增高＞300mm H2O者15例,脑室扩大行侧脑室引流者9例;12例给予两性霉素B（AmpB) 5氟胞嘧啶,6例又同时加氟康唑治疗,5例AmpB 氟康唑,1例单纯应用AmpB治疗。AmpB最大用量：AmpB10.05g 脂质体两性霉素B20g,平均用量2.6g;治愈17例,好转4例,死亡或自动出院5例。同时发现近5年隐球菌性脑膜炎病例数明显增多。结论 近年来,隐球菌性脑膜炎发病率明显增高,可能和免疫抑制剂和糖皮质激素的应用及HIV／AIDS增多有关,减少病死的关键在于提高早期诊断率,治疗仍首选AmpB加5氟胞嘧啶,侧脑室引流可减少AmpB的用量,提高治愈率,缩短疗程。     

Oral fluconazole therapy for patients with acquired immunodeficiency syndrome and cryptococcosis: experience with 22 patients

PURPOSE: Cryptococcus neoformans causes infections in up to 10 percent of patients with the acquired immunodeficiency syndrome (AIDS). Nearly 50 percent of AIDS patients with previously treated cryptococcal meningitis will experience a relapse within six months. To reduce the likelihood of relapse, a maintenance regimen of amphotericin B is often administered weekly. However, the drug's intravenous route of administration and considerable toxicity have led to a search for alternative antifungal agents. In this report, we document our experience with fluconazole, a new oral triazole antifungal agent. PATIENTS AND METHODS: Twenty-two patients with AIDS and various forms of cryptococcosis were treated in an open-label study with 50 to 400 mg/day of fluconazole. The following laboratory studies were done on a monthly basis: complete blood cell count, liver function tests, serum creatinine level, serum cryptococcal antigen level, and serum fluconazole level. Lumbar puncture was performed in patients with meningitis every four to eight weeks to evaluate cerebrospinal fluid cryptococcal antigen, India ink preparation findings, fungal culture, fluconazole level, and protein, glucose, and cell count. RESULTS: Of seven patients with active culture-positive infections, four showed clinical and microbiologic responses (three of four with meningitis, one of three with extraneural cryptococcosis). Fifteen patients who had already undergone successful amphotericin B therapy for either meningitis (n = 14) or pneumonia (n = 1) received fluconazole as prophylaxis against relapse. Fourteen patients remained free of infection during 11 to 64 weeks of suppressive therapy; one patient with meningitis experienced relapse after 26 weeks of treatment. Reverse reactions were limited to increases in hepatic enzyme levels in four patients. CONCLUSION: These results appear sufficiently encouraging to warrant further trials of this oral agent in the suppression of chronic cryptococcosis and perhaps in the treatment of acute infection.     

Initial treatment with amphotericin B plus rifampin in the acute treatment of cryptococcal meningitis in aids

The result of initial treatment with amphotericin B (0.7 mg/kg/day) plus rifampin (600 mg/day) for 2 weeks, followed by fluconazole (400 mg/day) for 8 weeks in the acute treatment of cryptococcal meningitis in AIDS is reported. There were 10 patients in the study: at 2 weeks, all had made a clinical response and cerebrospinal fluid was sterile in 4 patients; at 10 weeks, all had negative cerebrospinal fluid cultures. Serious side effects were not detected.     

Cryptococcal infection in AIDS.

Cryptococcus neoformans is an important opportunist pathogen in human immunodeficiency virus (HIV) infection. Cryptococcal meningitis (CM) 3rd after primary HIV neuropathy an Toxoplasma gondii among infectious neurological diseases in AIDS patients. Extrapulmonary infection due to C. neoformans has occurred in up to 13% of patients. 86% of the Cryptococcus spp isolates in the US, Canada, and Japan are serotype A. Thousands of infection due to var neoformans have been reported in AIDS patients but only 3 cases of var gattii. Cryptococcal pneumonia meningitis appears in 63-84% of AIDS patients with symptoms of fever, headache, meningism, and photophobia. 17-37% of AIDS patients with Cm die during therapy, and only 18-30% live over 12 months. Treatment in patients without immunodeficiency deficit is with a combination of .3 mg/kg/day of amphotericin B and 150 mg/kg/day of flucytosine for 4 weeks. A dose of .5-.8 mg/kg/day amphotericin was most effective although renal toxicity occurred in 80% of patients. Fluconazole has been used since 1987: cerebrospinal fluid concentrations reached 60-80% in serum. Treatment in 8 of 14 patients receiving 400 mg/day fluconazole failed while it did not in 6 patients treated with .7 mg/kg/day of amphotericin for 7 days and flucytosine 100 mg/kg/day. 200 mg/bid itraconazole was given to 32 patients with cryptococcosis (24 CM cases and 26 AIDS victims) and 65% of CM patients improved clinically with negative cultures. The relapse of 2 of 106 patients taking 200 mg/day fluconazole and 13 of 77 patients taking 1 mg/kg/week amphotericin B occurred in maintenance therapy. CM was suppressed in 10 of 15 patients with 400 mg/kg itrazonazole. Prophylactic use of azole drugs in AIDS does not protect completely from CM although it reduced systemic fungal infections such as cryptococcosis.     

Cryptococcal meningitis in the acquired immunodeficiency syndrome

Cryptococcosis is the most common, deep-seated fungal infection in AIDS patients, and cryptococcal meningitis is the most frequently observed syndrome. AIDS patients with cryptococcal meningitis usually have an indolent presentation and nonspecific findings on physical examination. Routine laboratory tests are of little assistance in diagnosing cryptococcal meningitis. Cerebrospinal fluid (CSF) white blood cell counts tend to be low, and glucose and protein levels are nonspecific. Serum cryptococcal antigen (CRAG) is a sensitive test for cryptococcal meningitis, and CSF CRAG is usually also positive. Definitive diagnosis is made by culture of the CSF. Therapy of cryptococcal meningitis is changing to antifungal agents that are easy to administer as outpatient therapy. Amphotericin B continues to be the primary antifungal used in initial treatment of cryptococcal meningitis; addition of flucytosine is of no benefit. Recent data suggest oral fluconazole is effective as primary therapy, and may be superior to amphotericin B as maintenance therapy. Maintenance therapy decreases the incidence of relapse and increases survival.     

A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. National Institute of Allergy and Infectious Diseases Mycoses Study Group.

This study was designed to compare the effectiveness of fluconazole vs. itraconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. HIV-infected patients who had been successfully treated (achieved negative culture of CSF) for a first episode of cryptococcal meningitis were randomized to receive fluconazole or itraconazole, both at 200 mg/d, for 12 months. The study was stopped prematurely on the recommendation of an independent Data Safety and Monitoring Board. At the time, 13 (23%) of 57 itraconazole recipients had experienced culture-positive relapse, compared with 2 relapses (4%) noted among 51 fluconazole recipients (P = .006). The factor best associated with relapse was the patient having not received flucytosine during the initial 2 weeks of primary treatment for cryptococcal disease (relative risk = 5.88; 95% confidence interval, 1.27-27.14; P = .04). Fluconazole remains the treatment of choice for maintenance therapy for AIDS-associated cryptococcal disease. Flucytosine may contribute to the prevention of relapse if used during the first 2 weeks of primary therapy.