JAC Advance Access published online on September 29, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl395
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1 Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201, Reus, Spain
* To whom correspondence should be addressed. Objectives: To develop proper treatments for patients who do not respond to current antifungal treatments, we tested new combinations of antifungal drugs for treating disseminated infections by Candida glabrata in a murine model. Methods: Mice were rendered neutropenic by intraperitoneal cyclophosphamide and intravenous 5-fluorouracil administration. The animals were infected intravenously with 2 x 108 cfu of C. glabrata. The efficacies of micafungin combined with amphotericin B, fluconazole or flucytosine, and of amphotericin B combined with fluconazole were evaluated by survival and tissue burden reduction. Results and Conclusions: Micafungin plus amphotericin B was the most effective combination at reducing tissue burden. Micafungin at 10 mg/kg combined with amphotericin B at 0.75, 1.5 or 3 mg/kg prolonged survival with respect to the monotherapies, but only the second combination showed a synergistic effect in reducing fungal load in spleen and kidney. Amphotericin B at 1.5 mg/kg combined with micafungin at 5, 10 or 20 mg/kg reduced tissue burden with respect to the monotherapies, but the effects of the three combinations were very similar. These results suggest that amphotericin B in combination with micafungin is promising for the treatment of disseminated C. glabrata infections.
Received June 28, 2006
Revised August 24, 2006
Accepted September 9, 2006
Brief report
Combined antifungal therapy in a murine infection by Candida glabrata
Marçal Mariné 1, Carolina Serena 1, F. Javier Pastor 1 *, and Josep Guarro 1
F. Javier Pastor, E-mail: franciscojavier.pastor{at}urv.cat
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