Combination of Oral Flucytosine and Ketoconazole as Therapy for Experimental Cryptococcal Meningitis

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Abstract
Ketoconazole, flucytosine and amphotericin B, alone and in 2-drug combinations, were used to treat cryptococcal meningitis in mice injected intracranially with Cryptococcus neoformans. Mortality was assessed; numbers of cryptococci in brain and liver were counted. By both of these parameters, the combination of flucytosine and ketoconazole produced results superior to those of either agent used alone. The standard combination of amphotericin B and flucytosine also showed an additive effect in this model. The combinatio nof amphotericin B and ketoconazole consistently showed no additive effect. None of the combinations of drugs was antagonistic. The results indicate a possible role for therapy with a combination of oral flucytosine and ketoconazole as part of the treatment for cryptococcal meningitis.