Itraconazole and flucytosine+itraconazole combination in the treatment of experimental cryptococcosis in hamsters

The efficacy of two different daily doses of itraconazole (ITRA) and the combination of flucytosine (5-FC) with ITRA in the treatment of an experimental model of cryptococcosis in hamsters was studied. Five groups of 20 Animals each were inoculated by the intracardiac route with 10(5) cells of Cryptococcus neoformans. Treatment started 3 days after the Infection, and was administered by gavage for 30 days. ITRA was applied at a daily dose of 25 mg kg-1 or 50 mg kg-1 and the combination of 5-FC and ITRA was given at 75 mg kg-1 day-1 or 50 mg kg-1 day-1 respectively. One group of 20 hamsters received the vehicle and was used as a control group. Treatment evaluation was based on the following parameters: number of surviving Animals 60 days after the infection; presence of encapsulated yeasts on microscopic examination of wet preparations of brain, lungs, liver, spleen and kidneys at necropsy; and brain qualitative (massive seeding) and quantitative cultures (determination of colony forming units, CFU). ITRA 50 (50 mg kg day-1) was the most effective treatment according to the studied parameters; 70% of brain cultures became negative and 95% of the treated hamsters survived to the end of the study period. ITRA efficacy was dose dependent. The combination of ITRA with 5-FC was less effective than administering the drugs separately; the reason for this finding is not known. The results obtained in this study should encourage the use of high doses of ITRA in cases of disseminated cryptococcosis in humans.