Efficacy of FK463, a Novel Water-Soluble Echinocandin-Like Lipopeptide, in Murine Models of Pulmonary Aspergillosis.

Y. WAKAI, S. MATSUMOTO, K. MAKI, E. WATABE, K. OTOMO, T. NAKAI, K. HATANO, Y. WATANABE, F. IKEDA, S. TAWARA, T. GOTO, F. MATSUMOTO, and S. KUWAHARA

Abstract: 

FK463 is a novel water soluble echinocandin-like lipopeptide that has demonstrated potent in vitro activity against Aspergillus fumigatus. The efficacy of FK463 was evaluated in murine models of pulmonary aspergillosis and was compared with those of fluconazole (FLCZ) and amphotericin B (AMPH-B). ICR mice were rendered neutropenic with intraperitoneally administered cyclophosphamide at 200 mg/kg 4 days before and 1 day after infection and were intranasally infected with conidia of A. fumigatus. The mice were intravenously treated with FK463, FLCZ and AMPH-B once daily for 4 days starting at 1.5 hours after infection. ED_{50} values were calculated based on the number of surviving mice at 15 days after infection. The ED_{50} values of FK463 against 3 strains of A. fumigatus (0.26-0.51 mg/kg) were lower than those of FLCZ (>20 mg/kg) and comparable to those of AMPH-B (0.26-0.46 mg/kg). In the Aspergillus target organ assay with neutropenic mice which determines lung counts at 5 days after infection under constantly maintained plasma levels of FK463 by a subcutaneously implanted osmotic pressure pump, a significant reduction in viable fungal cells in lungs was observed at plasma levels of 0.55 micro g/mL or higher of FK463. We conclude that FK463 is highly effective in treatment of pulmonary aspergillosis in an animal model.
1998

abstract No: 

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Full conference title: 

38th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 38th