Cotreatment with Aspirin and Azole Drugs Increases Sensitivity of Candida albicans in vitro

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 (MIC(50)) 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 MIC(50) 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.