JAC Advance Access published online on November 18, 2002
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkf247
© 2002 by The British Society for Antimicrobial Chemotherapy
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In Brief
1 School of Medicine, University
of Manchester; Hope Hospital,
Salford M6 8HD2
* Corresponding author. E-mail: pwarn{at}fs1.ho.man.ac.uk.
Received 9 May 2002
; revised 4 July 2002
; accepted 10 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
In vivo activity of micafungin
in a persistently neutropenic murine model of disseminated infection
caused by Candida tropicalis
2 School of Medicine, University
of Manchester
3 School of Medicine, University
of Manchester; Wythenshawe Hospital, Southmoor
Road, Manchester M23 9PL, UK
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