Pradimicins A, B and C: New antifungal antibiotics. II. In vitro and in vivo biological activities

Abstract

Pradimicins A, B and C specify novel antibiotics produced by Actinomadura hibisca No. P157-2 (ATCC 53557) possessing potent and broad antifungal activity in vivo. They showed moderate in vitro antifungal activity against a wide variety of fungi and yeasts including clinically important pathogens, and were highly effective in systemic infection with Candida albicans in mice after iv and im administrations. Pradimicin Ashowed in vivo therapeutic activity against C. albicans, Cryptococcus neoformans and Aspergillus fumigatus in both normal and immunocompromizedmice. 5-Fluorocytosine- and azole-resistant C. albicans strains were susceptible to pradimicin A. This antibiotic also demonstrated therapeutic efficacy against lung candidiasis and aspergillosis, vaginal candidiasis and skin Trichophyton mentagrophytes infection in mice with iv or topical treatment. The LD50 values after a single iv or im administration were 120mg/kg and more than 400mg/kg, respectively. Against various cultured mammalian cells, pradimicin A was noncytotoxic at 100 or 500 μg/ml, and showed potent anti-influenza virus activity with an IC50 value of 6.8 μg/ml. © 1990, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.