Perfect J R, Durack D T
J Infect Dis. 1982 Sep;146(3):429-35. doi: 10.1093/infdis/146.3.429.
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.
酮康唑、两性霉素B、5-氟胞嘧啶以及这些药物的联合用药被用作类固醇治疗的家兔慢性隐球菌性脑膜炎的疗法进行比较。用单一药物治疗患脑膜炎的家兔两小时后，5-氟胞嘧啶的脑脊液平均浓度为4.4微克/毫升，两性霉素B的浓度低于0.3微克/毫升，酮康唑的浓度范围为低于0.2至0.8微克/毫升。系列定量培养表明两性霉素B是最佳的单一药物治疗方案。酮康唑与氟胞嘧啶或治疗剂量的两性霉素联合使用两周时几乎没有或没有相加作用。然而，在为期两周的治疗方案中，酮康唑加两性霉素B的联合用药至少与两性霉素B加5-氟胞嘧啶一样有效。将酮康唑添加到低于治疗剂量的两性霉素B中可显著增强脑脊液中隐球菌的杀灭效果。
