Checkerboard Analysis to Calculate the Fractional Inhibitory Concentration (FIC) Index of Pathogenic Fungi for Drug Interaction
摘要
The emergence of antifungal resistance has led to the need for new strategies to combat fungal infections. One such strategy is the use of drug combinations that can potentially improve antifungal efficacy and circumvent resistance mechanisms. A common method for evaluating drug interactions is checkerboard analysis, which allows the determination of the FIC (Fractional Inhibitory Concentration) index, a quantitative measure of the interaction between two antifungal drugs (Bellio et al, MethodsX 8:101543 2021). In this method, different concentrations of two drugs are tested in a two-dimensional array of wells, with each combination tested over a range of concentrations. The FIC index (FICI) is calculated by evaluating the minimum inhibitory concentrations (MIC) of each drug in the combination, relative to its MIC when used alone (Meletiadis et al, Antimicrob Agents Chemother 54(2):602–609 2010). By testing different concentrations of two drugs in combination, we were able to identify the most effective combinations and evaluate their potential for synergistic effects. The FIC index shows considerable variability in the nature of the interactions, with some combinations showing strong synergistic effects, while others are additive, indifferent, or antagonistic. The results of the checkerboard analysis emphasize the potential of combination therapy in the treatment of fungal infections, particularly in pathogens that exhibit resistance to conventional antifungal agents. The studies, which focus on the molecular mechanisms underlying these interactions, could be crucial for the development of targeted combination therapies that can effectively counter the growing threat of antifungal resistance.