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JAC Advance Access originally published online on March 13, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 913-919
© 2003 The British Society for Antimicrobial Chemotherapy

Activity of micafungin (FK463) against an itraconazole-resistant strain of Aspergillus fumigatus and a strain of Aspergillus terreus demonstrating in vivo resistance to amphotericin B

P. A. Warn1,2,*, G. Morrissey1, J. Morrissey1 and D. W. Denning1,3

1 School of Medicine, University of Manchester, Manchester; 2 Department of Medicine, Hope Hospital, Salford M6 8HD; 3 Wythenshawe Hospital, Education and Research Centre, Southmoor Road, Manchester M29 9PL, UK

Received 8 January 2003; returned 25 January 2003; revised 30 January 2003; accepted 31 January 2003

We compared the activity of four doses of micafungin (FK463) with that of amphotericin B, liposomal amphotericin B and itraconazole in a murine model of disseminated aspergillosis. Temporarily neutropenic mice were infected with a lethal dose of either an itraconazole-resistant Aspergillus fumigatus isolate or Aspergillus terreus, a species that is less susceptible to amphotericin B. Treatment was started 24 h after infection and lasted for 7 days. Mice were treated with either amphotericin B (0.5 or 5 mg/kg), liposomal amphotericin (5 or 25 mg/kg), itraconazole (25 or 75 mg/kg) or FK463 (either 1, 2, 5 or 10 mg/kg). Treatment of the A. fumigatus model with either amphotericin B, liposomal amphotericin or FK463 prolonged survival. Doses of FK463 5 and 10 mg/kg had a 100% survival. Treatment of A. terreus infection with either itraconazole or FK463, but not amphotericin B, also prolonged survival. Doses of liposomal amphotericin of 5 and 25 mg/kg were ineffective against A. terreus infection. No treatment regime was able to totally clear the liver or kidneys in either model. The data indicate that FK463 may have a clinical role in the treatment of life-threatening invasive aspergillosis.

Keywords: micafungin, Aspergillus, murine, FK463, mouse

* Correspondence address. University of Manchester, Hope Hospital, Salford, Manchester M6 8HD, UK. Tel: +44-161-787-4420; Fax: +44-161-787-1495; E-mail: pwarn{at}fs1.ho.man.ac.uk


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