Cotreatment with aspirin and azole drugs increases sensitivity of candida albicans in vitro

Abstract

Purpose: This study aimed to investigate the effects of aspirin (acetyl salicylic acid [ASA]) combined with fluconazole (FCA), itraconazole (ITR), or voriconazole (VRC) on Candida albicans under planktonic and biofilm conditions. Methods: A total of 39 clinical C. albicans strains were used to perform the in vitro drug sensitivity assay under different conditions using the M27-A4 broth microdilution method. The minimal inhibitory concentrations (MICs) and fractional inhibitory concentration index (FICI) values were calculated. C. albicans ZY23 was chosen for the further analyses. Results: Under planktonic conditions, the half maximal MIC (MIC50) values of FCA, ITR, and VRC were 64-0.5 µg/mL, 32-0.0625 µg/mL, and 16-0.125 µg/mL, respectively, when applied, whereas in combination with ASA, the values decreased to 32-0.25 µg/mL, 8-0.0313 µg/mL, and 8-0.0313 µg/mL, respectively. Under biofilm conditions, FCA, ITR, or VRC alone showed MIC50 values of 128-8 µg/mL, 32-4 µg/mL, and 32-0.5 µg/mL, whereas in combination with ASA the values were decreased to 32-0.5 µg/mL, 16-0.5 µg/ mL, and 8-0.0625 µg/mL, respectively. Analysis of the FICI showed that the sensitization rate of ASA to FCA, ITR, and FCA under planktonic conditions was 43.59%, whereas the sensitization rates of ASP to FCA, ITR, and FCA under biofilm conditions were 46.15%, 46.15%, and 48.72%, respectively. Additionally, the time-growth and time-kill curves of C. albicans ZY23 further verified the synergistic effects of ASA on azole drugs. Conclusion: ASA may act as an enhancer of the inhibitory effects of azole drugs on the growth of clinical C. albicans under planktonic and biofilm conditions.