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JAC Advance Access originally published online on September 29, 2006
Journal of Antimicrobial Chemotherapy 2006 58(6):1295-1298; doi:10.1093/jac/dkl395
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Combined antifungal therapy in a murine infection by Candida glabrata

Marçal Mariné, Carolina Serena, F. Javier Pastor* and Josep Guarro

Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili Carrer Sant Llorenç 21, 43201, Reus, Spain

Received 28 June 2006; returned 12 August 2006; revised 24 August 2006; accepted 9 September 2006

*Corresponding author. Tel: +34-977-759359; Fax: +34-977-759322; E-mail: franciscojavier.pastor{at}urv.cat

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.

Keywords: candidiasis , animal models , micafungin , fluconazole , flucytosine


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