TREATMENT OF CRYPTOCOCCAL MENINGITIS ASSOCIATED WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME

Background Treatment with low-dose amphotericin B (0.4 mg per kilogram of body weight per day) or oral azole therapy in patients with the ac quired immunodeficiency syndrome (AIDS) and cryptococcal meningitis ha s been associated with high mortality and low rates of cerebrospinal f luid sterilization. Methods In a double-blind multicenter trial we ran domly assigned patients with a first episode of AIDS-associated crypto coccal meningitis to treatment with higher-dose amphotericin B (0.7 mg per kilogram per day) with or without flucytosine (100 mg per kilogra m per day) for two weeks (step one), followed by eight weeks of treatm ent with itraconazole (400 mg per day) or fluconazole (400 mg per day) (step two). Treatment was considered successful if cerebrospinal flui d cultures were negative at 2 and 10 weeks or if the patient was clini cally stable at 2 weeks and asymptomatic at 10 weeks. Results At two w eeks, the cerebrospinal fluid cultures were negative in 60 percent of the 202 patients receiving amphotericin B plus flucytosine and in 51 p ercent of the 179 receiving amphotericin B alone (P=0.06). Elevated in tracranial pressure was associated with death in 13 of 14 patients dur ing step one. The clinical outcome did not differ significantly betwee n the two groups. Seventy-two percent of the 151 fluconazole recipient s and 60 percent of the 155 itraconazole recipients had negative cultu res at 10 weeks (95 percent confidence interval for the difference in percentages, -100 to 21). The proportion of patients who had clinical responses was similar with fluconazole (68 percent) and itraconazole ( 70 per cent). Overall mortality was 5.5 percent in the first two weeks and 3.9 percent in the next eight weeks, with no significant differen ce between the groups. In a multivariate analysis, the addition of flu cytosine during the initial two weeks and treatment with fluconazole f or the next eight weeks were independently associated with cerebrospin al fluid sterilization. Conclusions For the initial treatment of AIDS- associated cryptococcal meningitis, the use of higher-dose amphoterici n B plus flucytosine is associated with an increased rate of cerebrosp inal fluid sterilization and decreased mortality at two weeks, as comp ared with regimens used in previous studies. Although consolidation th erapy with fluconazole is associated with a higher rate of cerebrospin al fluid sterilization, itraconazole may be a suitable alternative for patients unable to take fluconazole. (C) 1997, Massachusetts Medical Society.