JAC Advance Access originally published online on September 14, 2006
Journal of Antimicrobial Chemotherapy 2006 58(5):973-979; doi:10.1093/jac/dkl378
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Comparison of antifungal treatments for murine fusariosis
1 David Geffen School of Medicine at UCLA Los Angeles, CA, USA 2 Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center Torrance, CA, USA 3 Charles River Laboratories Davis, CA, USA 4 California State Polytechnic University Pomona, CA, USA
Received 30 May 2006; returned 2 August 2006; revised 3 August 2006; accepted 17 August 2006
*Corresponding author. Tel: +1-310-222-6424; Fax: +1-310-782-2016; E-mail: ibrahim{at}labiomed.org
Objectives: Fusarium solani infections are notoriously difficult to treat. We compared the efficacy of polyenes and an echinocandin in treating murine fusariosis to identify the optimal therapeutic regimen.
Methods: Neutropenic mice infected intravenously with F. solani were treated with amphotericin B (AmB), liposomal AmB (LAmB), amphotericin B lipid complex (ABLC), caspofungin acetate or a combination of LAmB and caspofungin. Treatment was initiated prior to infection (prophylactic therapy), 24 h post-infection (delayed therapy) or 2 days before infection and continued for 1 day after (continuous therapy).
Results: Prophylaxis only with LAmB significantly reduced brain or kidney fungal burden compared with placebo. No prophylactic treatment improved survival. LAmB levels in the kidneys were higher than ABLC or AmB levels, which were often undetectable. In the delayed therapy model, neither polyenes nor caspofungin improved survival. In the continuous therapy model, LAmB or LAmB plus caspofungin did not improve survival even though they did decrease fungal burden. In contrast, continuous caspofungin at 1 but not 5 mg/kg/day improved survival, but did not decrease fungal burden. Kidney inflammation and tissue necrosis were markedly decreased in mice treated with caspofungin compared with other treatments.
Conclusions: These studies demonstrate a dissociation between survival and tissue fungal burden during murine fusariosis. Although prophylactic LAmB may be useful at reducing tissue fungal burden, polyenes had limited survival benefit for active fusariosis. Caspofungin at 1 but not 5 mg/kg/day mediated surprising improvements in survival during active fusariosis, despite lack of reduction in fungal burden. Further studies are warranted.
Keywords: mice , antifungal therapy , Fusarium solani
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