COMPARATIVE-STUDY OF 6 ANTIFUNGAL TREATMENTS IN AN EXPERIMENTAL-MODEL OF MURINE CRYPTOCOCCOSIS

A comparative study, using 5 antifungal drugs for the treatment of an experimental model of murine cryptococcosis, was carried out. One hundred and eighty Balb C mice, divided in 18 groups of 10 animals each, were intraperitoneally inoculated with 10(7) cells of Cryptococcus neoformans var. neoformans. Twelve groups were treated with different schedules beginning 5 days after inoculation, for 2 or 4 weeks. The treatments were the following: amphotericin B (6 mg/kg/every other day, intraperitoneally); 5-fluorocytosine (300 mg/kg/day, by gavage); amphotericin B (6 mg/kg/every other day, intraperitoneally) in association with 5-fluorocytosine (300 mg/kg/day, by gavage); fluconazole, itraconazole and Sch 39.304 (all at the daily dose of 16 mg/kg, by gavage). The six remaining groups were used as controls and received the solvent for the drugs. The evaluation of the efficacy of the different treatments was based on: survival time; macroscopy of brain, lungs, liver and spleen at autopsies; presence of encapsulated yeasts in microscopic examination of wet preparations of these organs; and cultures of a concentrated suspension of brain and lungs. In the animals treated for 2 weeks, the combination of amphotericin B + 5-fluorocytosine was the most useful; it negativized the micro and macroscopic findings as well as 90% of the cultures, and prolonged the survival time up to 60 days. Sixty per cent of the mice which received amphotericin B exhibited the same survival time and macroscopic findings as those treated with the association of amphotericin B + 5-fluorocytosine. Among the azolic compounds, Sch 39.304 proved to be the most effective in the prolongation of survival time. None of the azoles showed differences with the control groups in the other parameters. In the mice treated for 4 weeks, the only treatment that achieved the negativization of brain and lung cultures, was the combination of amphotericin B and 5-fluorocytosine. Amphotericin B alone was better than the azolic compounds, improving the macro and microscopic results and prolonging the survival time. Sch 39.304 produced the same survival time as amphotericin B, but did not determine the biological cure. The other azoles as well as 5-fluorocytosine showed a minor increase in survival time, with no modifications of the other parameters when compared with the controls. All the drugs applied showed better results when they were administered for 4 weeks.