Efficacy of Nikkomycin Z in the Treatment of Murine Histoplasmosis

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.

将免疫健全ICR小鼠（Immune-competent ICR mice）与BALB/c无胸腺（裸）小鼠（BALB/c athymic (nude) mice）经静脉途径感染荚膜组织胞浆菌（Histoplasma capsulatum），随后分别给予氟康唑（fluconazole）、尼克霉素Z（nikkomycin Z）或5%葡萄糖溶液（5% dextrose，对照组）进行干预。在免疫健全ICR小鼠中，当以5 mg/kg体重的剂量每日两次给药时，氟康唑与尼克霉素Z均可延长小鼠生存期；当给药剂量低至2.5 mg/kg每日两次时，尼克霉素Z即可降低脾脏与肝脏中的真菌计数。两种药物联合使用时未出现拮抗作用，且联合治疗组的脾脏与肝脏真菌计数降低效果优于任一单一药物治疗组，但尼克霉素Z对脑组织真菌负荷无显著影响。在裸小鼠中，氟康唑与尼克霉素Z在延长生存期以及降低肝脏、脾脏真菌负荷方面表现出相加效应。尼克霉素Z耐受性良好，其疗效至少与氟康唑相当，且与氟康唑联合使用时可对鼠组织胞浆菌病（murine histoplasmosis）的治疗产生有益的相互作用。