Effect of Chemosensitizers on Minimum Inhibitory Concentrations of Fluconazole in Candida albicans

Objective: To evaluate the effect of chemosensitizers on the in vitro activity of fluconazole against Candida albicans strains. Materials and Methods: Using Clinical Laboratory Standard Institute method, antifungal activity of fluconazole was determined alone and in combination with 16 chemosensitizers that included verapamil, reserpine, quinine, quinidine, gemfibrozil, lansoprazole, tamoxifen, diltiazem, desipramine, nicardipine, cyclosporine, chlorpromazine, prochlorperazine, promethazine, thioridazine, and trifluoperazine. Further studies were done using double combinations of selected chemosensitizers with fluconazole (28 combinations). For testing combinations, half of the minimum inhibitory concentration (MIC) of each agent was selected in order to avoid the effect of the drug alone. One reference strain (ATCC90028) and one clinical isolate of C. albicans were used for testing the in vitro activity. Broth dilution method was used to determine the MICs of fluconazole and chemosensitizers. Results: Of the 16 chemosensitizers tested, 3 exhibited in vitro activity by increasing fluconazole susceptibility to 7-fold. The MICs of the reference strain and clinical isolate for fluconazole were 5.5 and 0.55 μg/ml, respectively, and these were reduced to 0.76 μg/ml by gemfibrozil, 0.83 μg/ml by quinine, and 0.76 μg/ml by chlorpromazine in the reference strain, with MIC reduction to 0.08 μg/ml by all three chemosensitizers in the clinical isolate. Some double combinations reduced the MIC of fluconazole to 10- to 100-fold, even when the chemosensitizers were not effective alone. Conclusion: The most effective double combinations were those of chlorpromazine with either reserpine or nicardipine.