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Amphotericin B resistance of Aspergillus terreus in a murine model of disseminated aspergillosis

Laboratoire de Parasitologie, Mycologie Médicale et Pathologie Exotique, Université Claude Bernard Lyon I, 8 Avenue Rockefeller, 69373 Lyon Cedex, France

Corresponding author: Dr E. Dannaoui (e-mail: edanna{at}rockefeller.univ-lyon1.fr).

Received 28 June 1999; revised version received 21 Dec. 1999; accepted 23 Dec. 1999.

Abstract

The in-vivo activity of amphotericin B and itraconazole against a clinical isolate of Aspergillus terreus was determined in a murine model of disseminated aspergillosis. MICs of amphotericin B and itraconazole for the strain, determined by an NCCLS-based technique, were 2 µg/ml and 1 µg/ml, respectively. Mice infected intravenously were treated with either itraconazole (50 or 100 mg/kg/day) or amphotericin B 4.5 mg/kg/day for 10 days. Treatment with both doses of itraconazole significantly prolonged the survival rates compared with those for untreated mice. In comparison, mortality rate and median survival time were identical for mice treated with amphotericin B and for mice given no therapy, indicating that the strain was highly resistant to amphotericin B in this model. Analysis of sterol composition showed that the major sterol was ergosterol. This suggests that amphotericin B resistance was not related to a modified sterol profile.

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