EFFICACY OF NIKKOMYCIN-Z IN THE TREATMENT OF MURINE HISTOPLASMOSIS

Immune-competent ICR and BALB/c athymic (nude) mice were infected intr avenously with Histoplasma capsulatum and treated with either fluconaz ole or nikkomycin Z or 5% dextrose (controls). In immune-competent ICR mice, fIuconazole 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 bo th the spleen and liver. When both drugs were combined, there was no a ntagonism, and in combined therapy spleen and liver counts were reduce d 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 eff ective as fluconazole, and may interact beneficially,vith fluconazole for treatment of murine histoplasmosis.