Journal Article

Alternative dosing regimens of liposomal amphotericin B (AmBisome) effective in treating murine systemic candidiasis

Jill P. Adler-Moore, Jon A. Olson and Richard T. Proffitt

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 54, issue 6, pages 1096-1102
Published in print December 2004 | ISSN: 0305-7453
Published online December 2004 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh460
Alternative dosing regimens of liposomal amphotericin B (AmBisome) effective in treating murine systemic candidiasis

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  • Medical Oncology
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Objectives: This study was done to determine whether high dose AmBisome (4–20 mg/kg), given intermittently, could reduce the frequency of dosing needed to treat murine systemic candidiasis when compared with conventional daily treatment.

Methods: Mice were immunosuppressed with cyclophosphamide every 3 days, beginning day −3 before challenge with log10 5.0 cfu Candida albicans. Treatment was begun 48–72 h post-challenge with daily or intermittent dose regimens of AmBisome, followed by determination of kidney cfu for up to 1 month post-treatment.

Results: A single AmBisome dose of 4 mg/kg was as effective as four daily, 1 mg/kg treatments. A total of 8 mg/kg, given as 4 mg/kg on days 2 and 4, or as 5 mg/kg on day 2 followed by 1 mg/kg on days 3, 4, and 5, also produced comparable efficacy. While 20 mg/kg given day 2, 4 and 6 post-challenge as a 1 week loading dose, followed by one 10 mg/kg treatment on day 13, decreased the fungal burden by up to 5 logs compared with controls (log10 2.3 cfu/g and log10 7.5 cfu/g, respectively), 20 mg/kg given Monday, Wednesday and Friday for 5 weeks, reduced the fungal burden to undetectable levels (i.e. log10 1.0 cfu).

Conclusions: Significant reduction or clearance of kidney cfu, following intermittent, high dose AmBisome treatment, indicated that non-daily dosing regimens could be successfully used instead of conventional daily dosing to treat established C. albicans infection in immunosuppressed mice.

Keywords: AmBisome loading dose; antifungal therapy; intermittent AmBisome dosing

Journal Article.  5233 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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