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.