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

Abstract

To determine 1) whether patients with coccidioidal meningitis who had achieved remission with oral azole therapy were cured and 2) when oral azole therapy could be discontinued in these patients. Data were gathered on patients with coccidioidal meningitis who had successfully responded to azole therapy in previous clinical trials. Referral centers, including university, county, and veterans' hospitals and clinics. 18 patients in whom azole therapy for meningitis had been discontinued, usually because of a presumption of cure. Clinical and cerebrospinal fluid relapse. 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 azole 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. Our data suggest 1) that disease is only suppressed in patients with meningitis who achieve remission while receiving azole therapy and 2) that discontinuing azole therapy is unsafe. The alternative is lifelong treatment with azoles; this appears to be acceptable, because toxicity is uncommon with triazole therapy, even long-term triazole therapy.