Is it ever safe to stop azole therapy for Coccidioides immitis meningitis?

Objective: To determine 1) whether patients with coccidioidal meningitis who had achieved remission with oral azole therapy were cured and 2) when oral atole therapy could be discontinued in these patients. Design: Data were gathered on patients with coccidioidal meningitis who had successfully responded to atole therapy in previous clinical trials. Setting: Referral centers, including university, county, and veterans' hospitals and clinics. Patients: 18 patients in whom atole therapy for meningitis had been discontinued, usually because of a presumption of cure. Main Outcome Measures: Clinical and cerebrospinal fluid relapse. Results: 14 of 18 patients (78% [95% CI, 52% to 94%]) had relapse with disseminated disease after discontinuation of therapy, for a total of 1 nonmeningeal and 15 meningeal relapses to date. Relapse occurred both soon and late (range, 0.5 to 30 months) after therapy was discontinued. The characteristics of patients who did not have relapse, including the particular atole used, the duration of therapy, the reason therapy was discontinued, and the cerebrospinal fluid indices before discontinuation, were similar to the characteristics of patients who had relapse. Relapse had serious consequences in some patients; 3 patients died. Conclusion: Our data suggest 1) that disease is only suppressed in patients with meningitis who achieve remission while receiving atole therapy and 2) that discontinuing atole therapy is unsafe. The alternative is lifelong treatment with azoles; this appears to be acceptable, because toxicity is uncommon with triazole therapy, even longterm triazole therapy.