The in-vivo activity of an antifungal antibiotic, benanomicin A, in comparison with amphotericin B and fluconazole.
The in-vivo antifungal activity of benanomicin A administered intravenously or subcutaneously was compared with that of amphotericin B and fluconazole using animal models of systemic infections with Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. The efficacy of benanomicin A in C. albicans infection was more pronounced when administered in multiple doses than in a single dose. This was also true of fluconazole, but not of amphotericin B, which showed no difference between single and multiple dosings. Benanomcin A eradicated C. albicans cells from the kidneys of infected mice in a manner comparable to that of amphotericin B, but more effectively than fluconazole. The histopathological findings obtained from the kidneys of the C. albicans-infected mice confirmed the therapeutic efficacy of benanomicin A. The subcutaneous ED50 values of benanomicin A were 1.30 mg/kg/day (C. albicans) and 19.0 mg/kg/day (A. fumigatus) which were intermediate between those of amphotericin B and fluconazole in the two models. The subcutaneous ED50 value of benanomicin A for C. neoformans was 21.5 mg/kg/day, which was higher than that of amphotericin B.
Ohtsuka
K
K
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, Yokohama, Japan.
Watanabe
M
M
Orikasa
Y
Y
Inouye
S
S
Uchida
K
K
Yamaguchi
H
H
Kondo
S
S
Takeuchi
T
T
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D002177:Candidiasis / Q000188:drug therapy; D003453:Cryptococcosis / Q000188:drug therapy / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy* / Q000473:pathology; D000095643:Pradimicins and Benanomicins
D000666:Amphotericin B; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D015725:Fluconazole; C056805:benanomicin A; D000095643:Pradimicins and Benanomicins