3--hydroxybenanomicin-a and Candidiasis

BMS 181184 (BMS), an analogue of pradimicin, was administered intravenously to neutropenic mice infected with either a fluconazole-susceptible or a fluconazole-resistant clinical isolate of Candida tropicalis. BMS prolonged survival at doses >3 mg kg -1 day-1, and at higher doses reduced tissue counts in mice. BMS was less potent mg for mg than amphotericin B. Combined BMS and amphotericin B were no more effective than either of the individual drugs.

Topics: Amphotericin B; Animals; Anthracyclines; Antibiotics, Antineoplastic; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Microbial; Fluconazole; Injections, Intravenous; Kidney; Mice; Microbial Sensitivity Tests; Spleen

BMS-181184 is a water-soluble derivative of the pradimicin group of antifungal compounds. We determined the in vitro activities of BMS-181184 and comparator agents amphotericin B, 5-fluorocytosine, fluconazole, and ketoconazole against 184 systemic fungal isolates collected at the Health Sciences Centre in Winnipeg, Canada, between 1987 and 1995. BMS-181184 demonstrated MICs of between 1 and 8 micrograms/mL for all Candida albicans, Candida glabrata, Candida tropicalis, Candida krusei, Candida lusitaniae, and Cryptococcus neoformans isolates tested. BMS-181184 was less active against Candida parapsilosis (MIC90 = 16 micrograms/mL) and Blastomyces dermatitidis (MIC90 = 32 micrograms/mL). Isolates of Candida species with fluconazole MICs of > or = 16 micrograms/mL and those with fluconazole MICs of < or = 8 micrograms/mL demonstrated similar BMS-181184 sensitivities.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Antifungal Agents; Blastomyces; Blastomycosis; Candida; Candidiasis; Cryptococcosis; Cryptococcus; Drug Resistance, Microbial; Fungemia; Humans; Microbial Sensitivity Tests

We compared the in vitro activity of BMS-181184, the first compound of a new class of antifungal agents, the pradimicins, with those of fluconazole and amphotericin B against 64 clinical isolates of Candida species. MICs were determined by a microdilution method with high resolution medium for BMS-181184 and fluconazole and antibiotic medium no. 3 with 2% glucose for amphotericin B. MICs of BMS-181184 for all yeasts were in the range of 0.78 to 12.5 micrograms/ml. BMS-181184 was active against isolates resistant to other antifungal agents, consistent with a novel mode of action. Minimum fungicidal concentrations for 16 isolates showed that BMS-181184 was fungicidal. Clinical studies are now required to confirm its activity.

Topics: Amphotericin B; Anthracyclines; Antibiotics, Antineoplastic; Antifungal Agents; Candida; Candidiasis; Fluconazole; Humans; Microbial Sensitivity Tests

Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Candidiasis; Cryptococcosis; Cyclophosphamide; Lethal Dose 50; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Structure-Activity Relationship