To evaluate the effect of corticosteroids on reducing elevated intracranial pressure in cryptococcal meningitis. To evaluate the safety of corticosteroids in patients with cryptococcal meningitis and intracranial hypertension.

In AIDS patients with cryptococcal meningitis, a correlation has been found between early death and elevated intracranial pressure. Since dexamethasone has been found to reduce intracranial pressure resulting from other forms of meningitis, it may be of benefit in AIDS patients with cryptococcal meningitis.

In AIDS patients with cryptococcal meningitis, a correlation has been found between early death and elevated intracranial pressure. Since dexamethasone has been found to reduce intracranial pressure resulting from other forms of meningitis, it may be of benefit in AIDS patients with cryptococcal meningitis.

Patients are randomized to receive dexamethasone or placebo every 6 hours for 72 hours (days 1 through 3). Additionally, standard antifungal therapy with amphotericin B and flucytosine is given for 2 weeks, followed by fluconazole for 8 weeks. Lumbar punctures will be performed daily on days 1 through 3, on days 7 and 14, and at week 10.

• Meningitis, Cryptococcal
• HIV Infections

• Drug: Flucytosine
• Drug: Fluconazole
• Drug: Amphotericin B
• Drug: Dexamethasone

Inclusion Criteria

Concurrent Medication:

Allowed:

• Aerosolized pentamidine or systemic chemoprophylaxis for PCP.
• Preventive therapy for steroid-associated ulcers and any other therapies required to manage steroid toxicity (e.g., insulin).

Patients must have:

• Documented initial episode or relapse of acute cryptococcal meningitis. (NOTE: Patients must be untreated for this episode except for administration of a test dose of 1 g or less amphotericin B.)
• Acute cryptococcal meningitis with cerebrospinal fluid opening pressure >= 250 mm H2O prior to receipt of antifungal therapy for this episode.
• Documented HIV infection OR a diagnosis of AIDS based on a documented AIDS-defining opportunistic infection.
• Ability to begin therapy within 8 hours after the pre-entry lumbar puncture.
• Consent of parent or guardian if less than 18 years of age.

NOTE:

• Comatose patients eligible provided informed consent can be provided by guardian or next of kin.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Concurrent CNS disease such as another infection or neoplasm that would interfere with assessment of response.
• Prison incarceration.

Concurrent Medication:

Excluded:

• Acetazolamide, mannitol, urea preparations, and other corticosteroids during the first 72 hours of the study.
• Treatment or prophylaxis with other systemic antifungal agents at any time.
• Antiretroviral therapy during the first 72 hours of the study.

Prior Medication:

Excluded within 7 days prior to study entry:

• Corticosteroids, mannitol, urea preparations, acetazolamide, or more than 24 hours of phenytoin.