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  • Sensitization of Candida albicans biofilms to various antifungal drugs by cyclosporine A.

Sensitization of Candida albicans biofilms to various antifungal drugs by cyclosporine A.

Annals of clinical microbiology and antimicrobials (2012-10-06)
Ravikumar B Shinde, Nitin M Chauhan, Jayant S Raut, Sankunny M Karuppayil
ABSTRACT

Biofilms formed by Candida albicans are resistant towards most of the available antifungal drugs. Therefore, infections associated with Candida biofilms are considered as a threat to immunocompromised patients. Combinatorial drug therapy may be a good strategy to combat C. albicans biofilms. Combinations of five antifungal drugs- fluconazole (FLC), voriconazole (VOR), caspofungin (CSP), amphotericin B (AmB) and nystatin (NYT) with cyclosporine A (CSA) were tested in vitro against planktonic and biofilm growth of C. albicans. Standard broth micro dilution method was used to study planktonic growth, while biofilms were studied in an in vitro 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. MICs of various antifungal drugs for planktonic growth of C. albicans 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. The combinations with CSA resulted 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 C. albicans infections.

MATERIALS
Product Number
Brand
Product Description

Nystatin, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Nystatin, ≥4,400 USP units/mg
Sigma-Aldrich
Nystatin, powder, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
Nystatin, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Nystatin Suspension, suspension, 10,000 unit/mL in DPBS, BioReagent, suitable for cell culture