JAC Advance Access originally published online on October 27, 2004
Journal of Antimicrobial Chemotherapy 2004 54(6):1096-1102; doi:10.1093/jac/dkh460
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JAC vol.54 no.6 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved
Alternative dosing regimens of liposomal amphotericin B (AmBisome) effective in treating murine systemic candidiasis
Department of Biological Sciences, California State Polytechnic University, Pomona, CA 91768, USA
* Corresponding author. Tel: +1-909-869-4047; Fax: +1-909-869-4078; Email: jpadler{at}csupomona.edu
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
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