Synergistic effects of amiodarone and fluconazole on Candida tropicalis resistant to fluconazole.
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.
Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast, LABEL, Federal University of Ceará, Fortaleza, CE, Brazil.
Cecília Rocha
CR
da Silva
João Batista
JB
de Andrade Neto
José Júlio Costa
JJ
Sidrim
Maria Rozzelê Ferreira
MR
Angelo
Hemerson Iury Ferreira
HI
Magalhães
Bruno Coêlho
BC
Cavalcanti
Raimunda Sâmia Nogueira
RS
Brilhante
Danielle Silveira
DS
Macedo
Manoel Odorico
MO
de Moraes
Marina Duarte Pinto
MD
Lobo
Thalles Barbosa
TB
Grangeiro
Hélio Vitoriano
HV
Nobre Júnior
D000638:Amiodarone / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D041022:Candida tropicalis / Q000187:drug effects* / Q000472:pathogenicity*; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D015725:Fluconazole; D000638:Amiodarone