Comparative study of six 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Bava
A J
AJ
Mycology Center, School of Medicine, University of Buenos Aires, Argentina.
Negroni
R
R
D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D003453:Cryptococcosis / Q000188:drug therapy*; D003455:Cryptococcus neoformans / Q000254:growth & development; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015725:Fluconazole / Q000627:therapeutic use; D005437:Flucytosine / Q000627:therapeutic use; D017964:Itraconazole; D007654:Ketoconazole / Q000031:analogs & derivatives / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D014230:Triazoles / Q000627:therapeutic use
D000935:Antifungal Agents; D014230:Triazoles; C056513:Sch 39304; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine; D007654:Ketoconazole