title: Treatment of experimental cryptococcal meningitis with fluconazole: impact of dose and addition of flucytosine on mycologic and pathophysiologic outcome.
abstract: Fluconazole is effective in the therapy of cryptococcal meningitis in patients with AIDS. The optimal dosage of fluconazole and the impact of combination with flucytosine are not known. In this study, rabbits with experimental cryptococcal meningitis were given fluconazole at low, intermediate, or high dose or in combination with a low or intermediate dose of flucytosine. Serial cerebrospinal fluid (CSF) examinations showed that all three doses of fluconazole and low-dose fluconazole in combination with intermediate-dose flucytosine were effective in reducing CSF cryptococcal titer, lactate, white blood cell count, and cryptococcal antigen (CRAG) titers. The intermediate and high doses of fluconazole reduced CSF fungal (P < .05) and CRAG (P < .001) titers earlier than low-dose fluconazole alone or in combination with flucytosine. Only the highest dose of fluconazole reduced brain edema after 7 days. In this model of cryptococcal meningitis, there was evidence of a dose response with fluconazole but no in vivo synergism with flucytosine.
authors.affiliation: Infectious Diseases Laboratory, San Francisco General Hospital, CA 94143-0811, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kartalija
authors.forename: K
authors.initials: K
authors.lastname: Kaye
authors.forename: J H
authors.initials: JH
authors.lastname: Tureen
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: M G
authors.initials: MG
authors.lastname: Täuber
authors.forename: B R
authors.initials: BR
authors.lastname: Elliott
authors.forename: M A
authors.initials: MA
authors.lastname: Sande
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D000946:Antigens, Fungal / Q000134:cerebrospinal fluid; D001929:Brain Edema / Q000188:drug therapy; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000276:immunology / Q000302:isolation & purification; D004359:Drug Therapy, Combination; D015725:Fluconazole / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D005437:Flucytosine / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D007773:Lactates / Q000134:cerebrospinal fluid; D019344:Lactic Acid; D007958:Leukocyte Count; D016919:Meningitis, Cryptococcal / Q000188:drug therapy* / Q000382:microbiology; D011817:Rabbits
chemical_list: D000935:Antifungal Agents; D000946:Antigens, Fungal; D007773:Lactates; D019344:Lactic Acid; D015725:Fluconazole; D005437:Flucytosine