Fluconazole therapy in coccidioidal meningitis maintained with intrathecal amphotericin B

Meningitis follows approximately 0.15% to 0.75% of cases of extrapulmonary coccidioidomycosis. Successful treatment of coccidioidal meningitis (CM) has generally required intrathecal therapy with amphotericin B, which often causes significant toxic effects and discomfort to the patient. Prior to fluconazole, azoles had not been efficacious in CM either because of toxicity at elevated doses or because of poor cerebrospinal fluid distribution. Fluconazole however, has been found to have both good cerebrospinal fluid penetration and a favorable side effect profile.

We studied 11 patients with CM who were maintained with amphotericin B and were then switched to oral fluconazole therapy alone at a dosage of 400 mg/d for a period of up to 19 months. The patients were evaluated clinically for evidence of deterioration measured by need for hospitalization, development of extrameningeal disease during the study period, need to reinstitute intrathecal amphotericin B therapy because of worsening disease, cerebrospinal fluid leukocyte count, protein level, and serologic tests for complement-fixing antibody.

Three patients required hospitalization during the study, two patients for reasons unrelated to CM. No patient developed extrameningeal disease or required discontinuation of fluconazole therapy because of deteriorating disease. Patients at exit reported no symptoms related to meningitis or adverse effects related to fluconazole therapy. There was no deterioration in general health or neurologic status.

Our study demonstrates that conversion from amphotericin B to fluconazole was associated with a stable disease course of CM for up to 19 months. Further studies delineating both optimal dosage and characteristics of patients likely to respond to fluconazole therapy alone are needed.