Synergistic Effects of Amiodarone and Fluconazole on Candida tropicalis Resistant to Fluconazole
Autor: | Hemerson Iury Ferreira Magalhães, Manoel Odorico de Moraes, Thalles B. Grangeiro, Marina Duarte Pinto Lobo, Raimunda Sâmia Nogueira Brilhante, Bruno C. Cavalcanti, José Júlio Costa Sidrim, Cecília Rocha da Silva, Danielle Silveira Macêdo, João Batista de Andrade Neto, Maria Rozzelê Ferreira Ângelo, Hélio Vitoriano Nobre Júnior |
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Rok vydání: | 2013 |
Předmět: |
Drug
Antifungal Agents media_common.quotation_subject Amiodarone Microbial Sensitivity Tests Drug resistance Pharmacology Amiodarona Candida tropicalis Drug Resistance Fungal medicine Pharmacology (medical) Mechanisms of Action: Physiological Effects Fluconazole media_common biology Drug Synergism Drug interaction biology.organism_classification Infectious Diseases Apoptosis Fluconazol medicine.drug Combination drug |
Zdroj: | Repositório Institucional da Universidade Federal do Ceará (UFC) Universidade Federal do Ceará (UFC) instacron:UFC |
ISSN: | 1098-6596 0066-4804 |
Popis: | 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. |
Databáze: | OpenAIRE |
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