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.
Orally administered amphotericin B (AmB) induced protective activity against infections due to vaccinia virus and Candida albicans in mice. This activity was also confirmed in immunocompromised mice. Analyses of the kinetics of peripheral blood cells treated with oral AmB indicated an increased ratio of polymorphonuclear leukocytes (PMN). Enhancement of γ-interferon (IFN) production and of NK-cell activity was also observed. The data were considered to indicate that γ-IFN produced by oral AmB has an important part as one of the factors protecting mice against both candidiasis and vaccinia virus infection.