JAC Advance Access published online on July 26, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki268
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1 School of Medicine, 1.800 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK
* To whom correspondence should be addressed. Objectives: To compare the activity of aminocandin (IP960), a new echinocandin with broad-spectrum in vitro activity against Aspergillus and Candida spp., with that of amphotericin B and fluconazole in a temporarily immunocompromised murine model of disseminated candidiasis. Methods: Mice were rendered neutropenic with cyclophosphamide and infected intravenously 3 days later with a fluconazole-resistant Candida tropicalis strain. Mice were treated with intraperitoneal amphotericin B (5 mg/kg/dose), oral fluconazole (50 mg/kg/dose), intravenous aminocandin (0.1-5 mg/kg/dose) or solvent control for 9 days. Mice were observed for survival and survivors were sacrificed 11 days post-infection. Kidneys, liver, brain and lungs were removed for semi-quantitative culture. Results: Control mice had 90-100% mortality. After infection with C. tropicalis, aminocandin 2.5 and 5 mg/kg/day and amphotericin B yielded 80% survival; aminocandin 1 mg/kg/day yielded 70% survival; aminocandin 0.25 and 0.1 mg/kg/day yielded 30% and 20% survival, respectively; and fluconazole 50 mg/kg/day and control regimens yielded 10% and 0-10% survival, respectively. Aminocandin 2.5 and 5.0 mg/kg/day and amphotericin B were superior in reducing mortality compared with aminocandin 0.25 and 0.1 mg/kg/day, fluconazole and controls (P < 0.047). The only regimen to reduce organ burdens below detectable levels was amphotericin B, which cleared 40% of mice. All organ burdens in the aminocandin 1.0, 2.5 and 5.0 mg/kg/day and amphotericin B regimens were significantly lower than other groups (P < 0.02). Conclusions: The data demonstrate that aminocandin at doses of
Received October 5, 2004
Revised June 29, 2004
Accepted June 30, 2005
Brief report
Activity of aminocandin (IP960) compared with amphotericin B and fluconazole in a neutropenic murine model of disseminated infection caused by a fluconazole-resistant strain of Candida tropicalis
2 School of Medicine, 1.800 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK; Wythenshawe Hospital, Southmoor Road, Manchester M23 9PL, UK
Peter A. Warn, E-mail: Peter.Warn{at}manchester.ac.uk
Abstract 
1.0 mg/kg/day is as effective as amphotericin B at improving survival and reducing organ burdens in this murine model of disseminated C. tropicalis.
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