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There have recently been significant increases in the prevalence of systemic invasive fungal infections. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of cross-resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapies have become one of the most widely used and effective strategies to alleviate this problem. Amiodarone (AMD) is classically used for the treatment of atrial fibrillation and is the drug of choice for patients with arrhythmia. Recent studies have shown broad antifungal activity of the drug when administered in combination with fluconazole (FLC). In the present study, we induced resistance to fluconazole in six strains of Candida tropicalis and evaluated potential synergism between fluconazole and amiodarone. The evaluation of drug interaction was determined by calculating the fractional inhibitory concentration and by performing flow cytometry. We conclude that amiodarone, when administered in combination with fluconazole, exhibits activity against strains of C. tropicalis that are resistant to fluconazole, which most likely occurs via changes in the integrity of the yeast cell membrane and the generation of oxidative stress, mitochondrial dysfunction, and DNA damage that could lead to cell death by apoptosis.

Citation

Cecília Rocha da Silva, João Batista de Andrade Neto, José Júlio Costa Sidrim, Maria Rozzelê Ferreira Angelo, Hemerson Iury Ferreira Magalhães, Bruno Coêlho Cavalcanti, Raimunda Sâmia Nogueira Brilhante, Danielle Silveira Macedo, Manoel Odorico de Moraes, Marina Duarte Pinto Lobo, Thalles Barbosa Grangeiro, Hélio Vitoriano Nobre Júnior. Synergistic effects of amiodarone and fluconazole on Candida tropicalis resistant to fluconazole. Antimicrobial agents and chemotherapy. 2013 Apr;57(4):1691-700

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PMID: 23357774

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