JAC Advance Access published online on March 13, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg185
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 School of Medicine, University
of Manchester, Manchester; Department
of Medicine, Hope Hospital,
Salford M6 8HD
* Corresponding author. E-mail: pwarn{at}fs1.ho.man.ac.uk.
Received 8 January 2003
; revised 25 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
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
2 School of Medicine, University
of Manchester, Manchester
3 School of Medicine, University
of Manchester, Manchester; Department
of Medicine, Hope Hospital,
Salford M6 8HD; Wythenshawe
Hospital, Education and Research Centre, Southmoor Road,
Manchester M29 9PL, UK
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