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  • Title: In vitro and in vivo antifungal activities of BMY-28864, a water-soluble pradimicin derivative.
    Author: Kakushima M, Masuyoshi S, Hirano M, Shinoda M, Ohta A, Kamei H, Oki T.
    Journal: Antimicrob Agents Chemother; 1991 Nov; 35(11):2185-90. PubMed ID: 1803990.
    Abstract:
    BMY-28864, a water-soluble pradimicin derivative, had potent in vitro activity against a wide variety of fungi, including those associated with deep-seated mycosis; it inhibited the growth of standard strains and clinical isolates at concentrations of 12.5 micrograms/ml or less. At the MIC or higher concentrations, BMY-28864 was fungicidal for Candida albicans under both growing and nongrowing conditions. BMY-28864 expressed fungicidal activity only in the presence of Ca2+, and its activity was totally diminished when ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), a Ca2+ chelator, was added to the test medium. The effectiveness of intravenously administered BMY-28864 in vivo was examined and compared with that of amphotericin B in mouse models of fungal infections. Both normal and cyclophosphamide-treated immunosuppressed mice infected with C. albicans, Cryptococcus neoformans, or Aspergillus fumigatus responded to therapy with BMY-28864 (50% protective doses of 17, 18, and 37 mg/kg of body weight in normal mice and of 32, 35, and 51 mg/kg in cyclophosphamide-treated mice, respectively). Lethal lung infections were also established with C. albicans or A. fumigatus in cyclophosphamide-treated mice. The 50% protective doses of BMY-28864 were 15 and 23 mg/kg per dose against C. albicans and A. fumigatus, respectively. The immunosuppression induced by intraperitoneal administration of 200 mg of cyclophosphamide per kg lasted for 5 days, and total recovery was observed by day 7.
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