FLUCONAZOLE THERAPY IN COCCIDIOIDAL MENINGITIS MAINTAINED WITH INTRATHECAL AMPHOTERICIN-B

Background: Meningitis follows approximately 0.15% to 0.75% of cases o f extrapulmonary coccidioidomycosis. Successful treatment of coccidioi dal meningitis (CM) has generally required intrathecal therapy with am photericin B, which often causes significant toxic effects and discomf ort to the patient. Prior to fluconazole, azoles had not been efficaci ous in CM either because of toxicity at elevated doses or because of p oor cerebrospinal fluid distribution. Fluconazole however, has been fo und to have both good cerebrospinal fluid penetration and a favorable side effect profile, Methods: We studied 11 patients with CM who were maintained with amphotericin B and were then switched to oral fluconaz ole therapy alone at a dosage of 400 mg/d for a period of up to 19 mon ths. The patients were evaluated clinically for evidence of deteriorat ion measured by need for hospitalization, development of extrameningea l disease during the study period, need to reinstitute intrathecal amp hotericin B therapy because of worsening disease, cerebrospinal fluid leukocyte count, protein level, and serologic tests for complement-fix ing antibody. Results: Three patients required hospitalization during the study, two patients for reasons unrelated to CM. No patient develo ped 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 fluconaz ole therapy. There was no deterioration in general health or neurologi c status. Conclusions: Our study demonstrates that conversion from amp hotericin B to fluconazole was associated with a stable disease course of CM for up to 19 months. Further studies delineating both optimal d osage and characteristics of patients likely to respond to fluconazole therapy alone are needed.