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.
Keywords: acetylsalicylic acid, synergistic effects, invasive fungus, virulence