A Study of Fluconazole in the Treatment of Cryptococcal Meningitis in Patients With AIDS

Inclusion Criteria Concurrent Medication: Allowed: * Antiviral therapy (e.g., zidovudine). * Prophylaxis (including aerosolized pentamidine) for Pneumocystis carinii pneumonia (PCP). Concurrent Treatment: Allowed: * Radiation therapy for mucocutaneous Kaposi's sarcoma. Patients must be oriented to person, place, and time and able to give written informed consent. * Patients must have had an acute episode of cryptococcal meningitis that was documented by recovery and identification of cryptococcus from lumbar cerebrospinal fluid (CSF) culture within 4 months of study entry. * Adequate therapy will consist of 6 - 16 weeks of treatment with amphotericin B alone, amphotericin B + oral flucytosine, or a period of the combination followed by amphotericin alone. Adequate regimens will include: * A minimum total amphotericin B dose of 2 grams as monotherapy. * 6 weeks of flucytosine at 150 mg/kg/day (or levels of 20 to 100 mcg/ml demonstrated) plus amphotericin B at an average daily dose of at least 0.3 mg/kg/day or to a total dose of 1 gram. * After a shorter period of the combination amphotericin/flucytosine therapy, an additional Y grams of amphotericin B monotherapy will make therapy adequate where Y = 2 gm-(X weeks combination therapy / 3 weeks). * For example, a patient who received 3 weeks of combination followed by amphotericin alone would need an additional 2 gm - 3 weeks/3 weeks = 1 gm of amphotericin B. * Patients need not be receiving amphotericin B at the time of randomization but must begin study maintenance therapy within 3 weeks of cessation of primary amphotericin B therapy. Prior Medication: Allowed: * Antiviral therapy (e.g., zidovudine (AZT)). * Prophylaxis (including aerosolized pentamidine) for Pneumocystis carinii pneumonia (PCP). Exclusion Criteria Co-existing Condition: Patients with the following are excluded: * Clinical evidence of acute or chronic meningitis based upon any etiology other than cryptococcosis. * History of allergy or intolerance of imidazoles, azoles, or amphotericin B. * Moderate or severe liver disease. Concurrent Medication: Excluded: * Intrathecal amphotericin B. * Coumarin-type anticoagulants. * Oral hypoglycemics. * Barbiturates. * Phenytoin. * Immunostimulants. * Investigational drugs or approved (licensed) drugs for investigational indications. Concurrent Treatment: Excluded: * Lymphocyte replacement. Patients with the following are excluded: * Clinical evidence of acute or chronic meningitis based upon any etiology other than cryptococcosis. * History of allergy or intolerance of imidazoles, azoles, or amphotericin B. * Moderate or severe liver disease defined by specific lab values. * Inability to take oral medications reliably. Prior Medication: Excluded: * Intrathecal amphotericin B. * Coumarin-type anticoagulants. * Oral hypoglycemics. * Barbiturates. * Phenytoin. * Immunostimulants. * Investigational drugs or approved (licensed) drugs for investigational indications. Prior Treatment: Excluded: * Lymphocyte replacement.