In Vivo Activity of Micafungin in a Persistently Neutropenic Murine Model of Disseminated Infection Caused Candida tropicalis

P. A. WARN, A. SHARP, G. MORRISSEY, D. DENNING

Author address: 

University Of Manchester, Manchester, United Kingdom.

Abstract: 

Background: Micafungin is a new candin antifungal agent with broad-spectrum in-vitro and in-vivo antifungal activity against both Aspergillus and Candida. We compared the activity of micafungin to that of amphotericin B and fluconazole in a persistently immunocompromised murine model of disseminated candidiasis against a strain of C.tropicalis that was resistant to amphotericin B and fluconazole in vitro. Methods: Mice were rendered persistently neutropenic with multiple doses of cyclophosphamide and infected intravenously with the C.tropicalis. Mice were treated 24 hours post infection with either intraperitoneal amphotericin B (0.5-5mg/kg/dose), oral fluconazole (50mg/kg BD), intravenous micafungin (1-10 mg/kg/dose) or solvent control for 7 days. Mice were sacrificed 11 days post infection and kidneys, lungs, brain and liver removed for quantitative culture.Results: Overall mortality in the model was low with rates varying between 10-25% in treatment groups (all mortality rates were not statistically different). All doses of micafungin were superior to amphotericin B at reducing organ burden in all organs. Micafungin 10mg/kg was superior to fluconazole at reducing organ burden. Other doses of micafungin tended to be superior to fluconazole but all did not reach statistical significance. Micafungin at doses between 2 and10mg/kg were the only regimes able to sterilize tissues infected with C.tropicalis. Conclusions: 1) Micafungin was well tolerated by the mice and was much more effective than amphotericin B or fluconazole against an amphotericin B and fluconazole resistant C.tropicalis. 2) Micafungin (>2mg/kg) was the only treatment able to sterilize mouse tissues in this persistently neutropenic model.
2002

abstract No: 

M-187

Full conference title: 

42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 42nd