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Heart drug might help fight chronic fungal infections

Johns Hopkins scientists have determined why a drug routinely used to treat heart arrhythmias might become a crucial addition to fighting chronic fungal infections, they report online in the Journal of Biological Chemistry.

Last year, scientists elsewhere noted the drug's ability to kill fungi. Now, a Johns Hopkins research team has found that amiodarone kills by disrupting cells' interior and exterior calcium balance.

Importantly, this is completely different from the way in which commonly used antifungal agents miconazole and fluconazole stop fungal growth, say the researchers. In their experiments, a combination of amiodarone and either of the "azoles" killed dramatically more fungi than expected.

"This antiarrhythmic drug, in low doses, combined with azoles looks very promising in the lab and appears to be worth taking a look at clinically," says Rajini Rao, Ph.D., associate professor of physiology in the Johns Hopkins School of Medicine's Institute for Basic Biomedical Sciences. "The azoles prevent fungi from growing, but don't actually kill them -- the immune system is supposed to do that. Amiodarone kills them instead of keeping them dormant."

While fungal infections in general are easy to get rid of, in patients with depressed immune systems or with conditions like cystic fibrosis that increase susceptibility to chronic or recurring fungal infections, prolonged use of azoles can lead to the fungus becoming resistant to treatment. Finding a way to treat severe and life-threatening fungal infections with an option that boosts the effects of azoles without relying on the strength of the immune system is attractive, says Rao, who studies how calcium is brought into cells.

"Importantly, amiodarone and miconazole or fluconazole were synergistic, killing more fungus together than expected by just adding their individual results," says Rao. "What we've learned about amiodarone's effects on cellular calcium lev
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
5-Jun-2003


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