Efficacy and safety of fluconazole conbined with amphotericin B for treatment of cryptococcal meningitis in patients with AIDS

Abstract

Cryptococcal meningitis is the most common life-threatening opportunistic fungal infection in patients with AIDS. The purpose of this study were to compare the efficacy and safety of giving high dose of amphotericin B for the first two weeks of therapy with or without fluconazole. The patients were observed for the total of eight weeks. The study was carried out in 72 cryptococcal meningitis patients with AIDS, at Bamrasnaradura Hospital. Most of the patients were male (77.8%) ranging in aged from 20 to 29 years. The most common clinical symptoms were headache (97.2%), nausea or vomiting (84.7%) and fever (59.7%). Cerebrospinal fluid (CSE) pressure was higher than 200 mmH2O (91.7%) and white blood cells were less than 20 cells/mm3 (76.4%). For the first 2 weeks, 38 patients were randomly assigned to receive amphotericin B (0.7 mg/kg/d) plus fluconazole (800 mg loading dose on the first day and 400 mg daily on the later day, AMB+FLU) and 34 patients toreceive amphotericin B alone (AMB) in the same dose for two weeks. The following six weeks both groups were treated with fluconazole (400 mg daily or 200 mg daily once the patients was found to have a first negative CSF culture). Treatment outcome was considered to be successful if the patient showed improvement in clinical signs and symptoms together with two consecutive negative CSF culture at least one week apart. Outcomes of the patients at two weeks showed that majority of the patients in both groups had clinical outcome improvement but the mycological outcome was still persistence. The negative CSF cultures were found in 9 patients (23.7%) who received AMB+FLU and 11 patients (32.4%) who received AMB which was not statistically significant diffence (P = 0.37). At eight weeks of therapy, the successful outcomes were found in 24 patients (63.2%) who received AMB+FLU and 22 patients (64.7%) who received AMB (P = 0.47). The median time to the first negative CSF culture was 4 weeks in each group. The mortality rate in the first two weeks was 13.2% in the AMB+FLU group and 14.7% in the AMB group which were not statisticlly significant (P = 1.00). None of the patients required discontinuance of the drugs during therapy due to adverse drug reactions. These results suggest that treatment of CM in patients with AIDS by the using fluconazole combined with amphotericin B in the first two week did not increase either the efficacy in term of sterilization of CSF culture or the adverse drug reactions when compared with the results obtained from the usage of amphotericin B alone. The regimen using high dose of amphotericin B alone for two weeks in this study resulted in the success rate of 64.7% which was higher than the success rate of 35-50% reported by other studies. This regimen is therefore recommended for future therapy.