Journal
MEDICAL MYCOLOGY
Volume 48, Issue 2, Pages 255-262Publisher
OXFORD UNIV PRESS
DOI: 10.3109/13693780903081968
Keywords
fluconazole; astemizole; Cryptococcus neoformans; fungicidal; drug
Categories
Funding
- NIHAID
Ask authors/readers for more resources
Cryptococcus neoformans is the leading cause of fungal meningitis, a life-threatening infection that occurs predominately in immuocompromised patients. Current drug therapies are limited to amphotericin B, flucytosine and the azoles since the echinocandins have no demonstrated activity against yeast like pathogens. Fluconazole, a drug belonging to the azole class and often the only available antifungal in the developing world, is fungistatic and therefore not effective in clearing cryptococcal infections in immunosuppressed individuals. Here we report that astemizole and a closely related analog (A2) promoted in vitro fungicidal activity of fluconazole against Cryptococcus neoformans var. grubii and Cryptococcus gattii. Astemizole, a second-generation antihistamine drug used as an H-1 antagonist, has also been found to have antimalarial activity. Disk diffusion assays and MIC and MFC analysis confirmed that the inhibitory concentrations of these drug combinations were fungicidal. When tested in vivo, astemizole or A2 in combination with fluconazole significantly improved the survival of Galleria mellonella (wax moth caterpillar) that had been previously challenged with C. neoformans but not when caterpillars were challenged with a fluconazole-resistant strain. The findings reported here suggest that fungicidal combinations between azoles and other existing drugs may represent an alternative strategy for improving treatments for fungal infections.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available