TREATMENT OF EXPERIMENTAL CRYPTOCOCCAL MENINGITIS WITH FLUCONAZOLE - IMPACT OF DOSE AND ADDITION OF FLUCYTOSINE ON MYCOLOGICAL AND PATHOPHYSIOLOGIC OUTCOME

Fluconazole is effective in the therapy of cryptococcal meningitis in patients with AIDS, The optimal dosage of fluconazole and the impact o f combination with flucytosine are not known. In this study, rabbits w ith experimental cryptococcal meningitis were given fluconazole at low , intermediate, or high dose or in combination with a low or intermedi ate dose of flucytosine. Serial cerebrospinal fluid (CSF) examinations showed that all three doses of fluconazole and low-dose fluconazole i n combination with intermediate-dose flucytosine were effective in red ucing CSF cryptococcal titer, lactate, white blood cell count, and cry ptococcal antigen (CRAG) titers, The intermediate and high doses of fl uconazole reduced CSF fungal (P < .05) and CRAG (P < .001) titers earl ier than low-dose fluconazole alone or in combination with flucytosine . Only the highest dose of fluconazole reduced brain edema after 7 day s, In this model of cryptococcal meningitis, there was evidence of a d ose response with fluconazole but no in vivo synergism with flucytosin e.