Sensitization of <it>Candida albicans</it> biofilms to various antifungal drugs by cyclosporine A

Abstract

<p>Abstract</p> <p>Background</p> <p>Biofilms formed by <it>Candida albicans</it> are resistant towards most of the available antifungal drugs. Therefore, infections associated with <it>Candida</it> biofilms are considered as a threat to immunocompromised patients. Combinatorial drug therapy may be a good strategy to combat <it>C. albicans</it> biofilms.</p> <p>Methods</p> <p>Combinations of five antifungal drugs- fluconazole (FLC), voriconazole (VOR), caspofungin (CSP), amphotericin B (AmB) and nystatin (NYT) with cyclosporine A (CSA) were tested <it>in vitro</it> against planktonic and biofilm growth of <it>C. albicans</it>. Standard broth micro dilution method was used to study planktonic growth, while biofilms were studied in an <it>in vitro</it> biofilm model. A chequerboard format was used to determine fractional inhibitory concentration indices (FICI) of combination effects. Biofilm growth was analyzed using XTT-metabolic assay.</p> <p>Results</p> <p>MICs of various antifungal drugs for planktonic growth of <it>C. albicans</it> were lowered in combination with CSA by 2 to 16 fold. Activity against biofilm development with FIC indices of 0.26, 0.28, 0.31 and 0.25 indicated synergistic interactions between FLC-CSA, VOR-CSA, CSP-CSA and AmB-CSA, respectively. Increase in efficacy of the drugs FLC, VOR and CSP against mature biofilms after addition of 62.5 μg/ml of CSA was evident with FIC indices 0.06, 0.14 and 0.37, respectively.</p> <p>Conclusions</p> <p>The combinations with CSA re<it>s</it>ulted in increased susceptibility of biofilms to antifungal drugs. Combination of antifungal drugs with CSA would be an effective prophylactic and therapeutic strategy against biofilm associated <it>C. albicans</it> infections.</p

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