In Vivo Efficacies of Pradimicin Derivatives, BMS-181184 and BMY-28864, and Benanomicin A against Systemic Candida albicans and Aspergillus fumigatus Infections in Neutropenic Mice

Abstract

The in vivo efficacies of pradimicin derivatives, BMS-181184 and BMY-28864, and benanomicin A were evaluated comparatively in experimental systemic candidiasis and aspergillosis in cyclophosphamide-treated neutropenic mice. Compounds were given intravenously once daily for 5 consecutive days beginning immediately after the infection of 10LD₅₀ of either Candida albicans A9540 or Aspergillus fumigatus IAM 2034. BMS-181184 was most effective in reducing the mortality among mice infected with C. albicans A9540, giving a PD₅₀ value of 33mg/kg/day, while BMY-28864 and benanomicin A gave PD₅₀ values of 50 and 71mg/kg/day, respectively. Against A. fumigatus IAM 2034, BMS-181184 and BMY-28864 were equally effective, giving PD₅₀ values of 41 and 43mg/kg/day, respectively, while benanomicin A was less effective, giving a PD₅₀ value of 81mg/kg/day.