Graybill J R, Najvar L K, Bocanegra R, Hector R F, Luther M F
Audie Murphy Memorial Veterans Hospital, San Antonio, Texas 78284, USA.
Antimicrob Agents Chemother. 1998 Sep;42(9):2371-4. doi: 10.1128/AAC.42.9.2371.
Immune-competent ICR and BALB/c athymic (nude) mice were infected intravenously with Histoplasma capsulatum and treated with either fluconazole or nikkomycin Z or 5% dextrose (controls). In immune-competent ICR mice, fluconazole and nikkomycin Z both prolonged survival when given at 5 mg/kg of body weight twice daily. When administered in doses as low as 2.5 mg/kg twice daily, nikkomycin Z reduced fungal counts in both the spleen and liver. When both drugs were combined, there was no antagonism, and in combined therapy spleen and liver counts were reduced more than for either drug alone. However, nikkomycin Z had no effect on brain fungal burden. In nude mice fluconazole and nikkomycin Z had an additive effect in prolongation of survival and reduction of liver and spleen burden. Nikkomycin Z is well tolerated, is at least as effective as fluconazole, and may interact beneficially with fluconazole for treatment of murine histoplasmosis.
将荚膜组织胞浆菌经静脉注射感染具有免疫活性的ICR小鼠和无胸腺（裸）BALB/c小鼠，并分别用氟康唑、尼可霉素Z或5%葡萄糖（对照组）进行治疗。在具有免疫活性的ICR小鼠中，每日两次给予5mg/kg体重的氟康唑和尼可霉素Z均能延长生存期。当每日两次给予低至2.5mg/kg剂量的尼可霉素Z时，可降低脾脏和肝脏中的真菌数量。当两种药物联合使用时，不存在拮抗作用，联合治疗时脾脏和肝脏中的真菌数量比单独使用任一药物时减少得更多。然而，尼可霉素Z对脑部真菌负荷没有影响。在裸鼠中，氟康唑和尼可霉素Z在延长生存期和减轻肝脏及脾脏负担方面具有相加作用。尼可霉素Z耐受性良好，至少与氟康唑一样有效，并且在治疗小鼠组织胞浆菌病时可能与氟康唑产生有益的相互作用。
