Treatment of experimental cryptococcal meningitis with amphotericin B, 5-fluorocytosine, and ketoconazole.
Ketoconazole, amphotericin B, 5-fluorocytosine, and combinations of these drugs were compared as therapy for chronic cryptococcal meningitis in steroid-treated rabbits. Two hours after treatment of rabbits with meningitis with single drugs the mean cerebrospinal fluid concentration of 5-fluorocytosine was 4.4 microgram/ml, that of amphotericin B was less than 0.3 microgram/ml, and that of ketoconazole ranged from less than 0.2 to 0.8 microgram/ml. Serial quantitative cultures indicated that amphotericin B was the best single-drug regimen. Ketoconazole provided little or no additive effect when used in combination with fluorocytosine or therapeutic doses of amphotericin for two weeks. However, the combination of ketoconazole plus amphotericin B was at least as effective as amphotericin B plus 5-fluorocytosine over a two-week treatment regimen. The addition of ketoconazole to subtherapeutic dose of amphotericin B significantly increased the killing of cryptococci in cerebrospinal fluid.
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D003453:Cryptococcosis / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D003455:Cryptococcus neoformans / Q000187:drug effects; D003596:Cytosine / Q000031:analogs & derivatives*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005437:Flucytosine / Q000627:therapeutic use*; D007093:Imidazoles / Q000627:therapeutic use*; D007654:Ketoconazole; D008297:Male; D008581:Meningitis / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D011817:Rabbits
D007093:Imidazoles; D010879:Piperazines; D000666:Amphotericin B; D003596:Cytosine; D005437:Flucytosine; D007654:Ketoconazole