COMPARISON OF FLUCONAZOLE, AMPHOTERICIN-B AND FLUCYTOSINE IN TREATMENT OF A MURINE MODEL OF DISSEMINATED INFECTION WITH CANDIDA-GLABRATA INIMMUNOCOMPROMISED MICE

Candida glabrata is an emerging opportunist pathogen in immunosuppress ed patients. C. glabrata is resistant to many antifungal agents and un til recently, there have been no standard treatment regimens for this organism. A mouse model was established using mice immunosuppressed wi th 5 fluorouracil to evaluate amphotericin B, flucytosine, fluconazole and their combinations to treat an intravenously induced C. glabrata infection. Treatment with fluconazole, flucytosine, amphotericin B or a combination was begun one day after infection. Following 5 days of t reatment, the mice were killed for fungal counts in kidneys and spleen . At the doses used, amphotericin B was superior to fluconazole or flu cytosine alone in the treatment of C. glabrata infections. Flucytosine reduced the fungal burden in the kidney for only two of four isolates of C. glabrata. The combination of fluconazole and flucytosine was su perior to these agents alone in reducing the tissue burden in the kidn ey for one isolate of C. glabrata. High doses of fluconazole alone pro duced modest reductions in kidney counts but did not reduce spleen tis sue counts. There was poor correlation between in-vitro MICs and in-vi vo results.