JAC Advance Access originally published online on November 18, 2002
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Journal of Antimicrobial Chemotherapy (2002) 50, 1071-1074
© 2002 The British Society for Antimicrobial Chemotherapy
In vivo activity of micafungin in a persistently neutropenic murine model of disseminated infection caused by Candida tropicalis
1 School of Medicine, University of Manchester; 2 Hope Hospital, Salford M6 8HD2; 3 Wythenshawe Hospital, Southmoor Road, Manchester M23 9PL, UK
Received 9 May 2002; returned 4 July 2002; revised 10 September 2002; accepted 13 September 2002
Micafungin is a new echinocandin with broad-spectrum in vitro and in vivo antifungal activity against both Aspergillus and Candida species. We compared the activity of micafungin with that of amphotericin B and fluconazole in a persistently immunocompromised murine model of disseminated candidiasis against a strain of Candida tropicalis that was resistant to amphotericin B and fluconazole in vitro. Mice were rendered persistently neutropenic with multiple doses of cyclophosphamide and infected intravenously with C. tropicalis. Mice were treated with either intraperitoneal amphotericin B (0.5–5 mg/kg per dose), oral fluconazole (50 mg/kg twice a day), intravenous micafungin (1–10 mg/kg per dose) or solvent control for 7 days. Mice were killed at 11 days post-infection and kidneys, lungs, brain and liver removed for quantitative culture. Overall mortality in the model was low, with rates varying between 10% and 25% in treatment groups. Micafungin at doses between 2 and 10 mg/kg were the only regimes able to reduce cfu below the level of detection of tissues infected with C. tropicalis. 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.
Keywords: micafungin, murine, Aspergillus
* Corresponding author. Tel: +44-161-787-4420; Fax: +44-161-787-1495; E-mail: pwarn{at}fs1.ho.man.ac.uk
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