Oral Itraconazole Therapy of Cryptococcal Meningitis and Cryptococcosis in Patients with AIDS

We studied the efficacy of oral itraconazole in 57 AIDS patients with cryptococcosis. Diagnoses included cryptococcal meningitis (48 patients), cryptococcemia (28 patients), cryptococcuria (16 patients), pulmonary cryptococcosis (12 patients), and 2 patients who were symptomatic, antigen positive and culture negative. Patients received itraconazole 200 mg b.i.d. orally given as sole therapy in 55 of 57 (96%); five patients with low serum concentrations received 200 mg t.i.d. Therapy was monitored by clinical and radiological response, culture and cryptococcal antigen testing. Twenty three of 36 (64%) evaluable patients with cryptococcal meningitis had complete responses (clinical resolution and negative cultures), 8 (22%) a partial response and 5 (14%) failed therapy. In those not previously treated, only 2 of 29 (7%) failed therapy. Meningitis recrudesced on therapy in 13 of 31 (42%) responding patients; the median time to recrudescence in these 13 patients was 4 months after starting itraconazole. Cryptococcemia was abolished in 17 of 19 (89%) evaluable patients together with clinical resolution. Among the 9 evaluable patients with pulmonary cryptococcosis, 8 have responded to therapy (89%). Cryptococcuria was abolished in 4 of 10 (40%) evaluable patients. Among the whole group of 57 patients, relapse occurred in 4 of 7 (57%) patients discontinuing therapy. Prior or concurrent therapy with rifampin (for mycobacterial disease) was associated with one patient failing therapy and another having to be withdrawn with no response at eight days. Our response rates compare favorably to amphotericin B therapy with or without flucytosine. Eighty-five of 96 (91%) isolates of C. neoformans were susceptible in vitro to itraconazole (MIC≤3.13 mcg/ml), 6 were borderline (MIC 6.25 mcg/ml) and 3 were resistant (≥12.5 mcg/ml). Oral itraconazole is promising for the primary or salvage therapy of cryptococcal meningitis and other forms of cryptococcosis in patients with AIDS.