دورية
Caspofungin Inhibits Rhizopus oryzae1,3-β-d-Glucan Synthase, Lowers Burden in Brain Measured by Quantitative PCR, and Improves Survival at a Low but Not a High Dose during Murine Disseminated Zygomycosis
| العنوان: | Caspofungin Inhibits Rhizopus oryzae1,3-β-d-Glucan Synthase, Lowers Burden in Brain Measured by Quantitative PCR, and Improves Survival at a Low but Not a High Dose during Murine Disseminated Zygomycosis |
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| المؤلفون: | Ibrahim, Ashraf S., Bowman, Joel C., Avanessian, Valentina, Brown, Keturah, Spellberg, Brad, Edwards, John E., Douglas, Cameron M. |
| المصدر: | Antimicrobial Agents and Chemotherapy; February 2005, Vol. 49 Issue: 2 p721-727, 7p |
| مستخلص: | ABSTRACTRhizopus oryzaeis the most common cause of zygomycosis, a life-threatening infection that usually occurs in patients with diabetic ketoacidosis. Despite standard therapy, the overall rate of mortality from zygomycosis remains >50%, and new strategies for treatment are urgently needed. The activities of caspofungin acetate (CAS) and other echinocandins (antifungal inhibitors of the synthesis of 1,3-β-d-glucan synthase [GS]) against the agents of zygomycosis have remained relatively unexplored, especially in animal models of infection. We found that R. oryzaehas both an FKSgene, which in other fungi encodes a subunit of the GS synthesis complex, and CAS-susceptible, membrane-associated GS activity. Low-dose but not high-dose CAS improved the survival of mice with diabetic ketoacidosis infected with a small inoculum but not a large inoculum of R. oryzae. Fungal burden, assessed by a novel quantitative PCR assay, correlated with increasing inocula and progression of disease, particularly later in the infection, when CFU counts did not. CAS decreased the brain burden of R. oryzaewhen it was given prophylactically but not when therapy was started after infection. These results indicate that CAS has significant but limited activity against R. oryzaein vivo and demonstrates an inverse dose-response effect. The potential for CAS to play a role in combination therapy against zygomycosis merits further investigation. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 00664804 10986596 |
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| DOI: | 10.1128/AAC.49.2.721-727.2005 |