In vitro and in vivo antifungal activities of BMY-28864, a water-soluble pradimicin derivative.

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.

• Authors: M Kakushima, S Masuyoshi, M Hirano, M Shinoda, A Ohta, H Kamei, T Oki
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 35 Issue 11 Pg. 2185-90 (Nov 1991) ISSN: 0066-4804 [Print] United States
• PMID: 1803990 (Publication Type: Journal Article)

Chemical References

• Anthracyclines
• Antibiotics, Antineoplastic
• Antifungal Agents
• Culture Media
• N,N-dimethylpradimicin FA-2
• Egtazic Acid
• Amphotericin B
• Calcium

Topics

• Amphotericin B (therapeutic use)
• Animals
• Anthracyclines
• Antibiotics, Antineoplastic (pharmacology, therapeutic use)
• Antifungal Agents (pharmacology, therapeutic use)
• Calcium (physiology)
• Culture Media
• Egtazic Acid (pharmacology)
• Fungi (drug effects)
• Immunosuppression Therapy
• Lung Diseases, Fungal (drug therapy, microbiology)
• Male
• Mice
• Mice, Inbred ICR
• Microbial Sensitivity Tests
• Mycoses (drug therapy, microbiology)