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

Abstract

PurposeThis 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.MethodsA 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.ResultsUnder 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.ConclusionASA may act as an enhancer of the inhibitory effects of azole drugs on the growth of clinical C. albicans under planktonic and biofilm conditions.