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 (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.

Bioprospecting, Synergistic Antifungal and Toxicological Aspects of the Hydroxychalcones and Their Association with Azole Derivates against Candida spp. for Treating Vulvovaginal Candidiasis

“…All the combinations demonstrated promising antifungal results, highlighting the combinations of 2-HC + 3′-HC, with MIC values of 3.9 to 7.8 mg/L improving antifungal activity when compared to the individual effect and, in turn, demonstrated a synergistic effect against all three of the Candida species observed. On the other hand, the 2-HC + FCZ combination demonstrated high antifungal activity, with MICs of 15.6 to 0.06 mg/L, in addition to exhibiting a synergistic C. krusei and additive effect against C. tropicalis, species genetically resistant to FCZ [43,65].…”

“…For the interpretation of the checkerboard, the "Lowest Fractional Inhibitory Concentration Index" (FICI) method of each well of the growth and non-growth interface, as proposed by Feng et al (2021) and Feng and Yang (2023) [42,43]. The wells with more than 80% fungal growth inhibition were used to limit the interface.…”

In Vitro Antimycobacterial Activity of Human Lactoferrin-Derived Peptide, D-hLF 1-11, against Susceptible and Drug-Resistant Mycobacterium tuberculosis and Its Synergistic Effect with Rifampicin

“…The experiment is conducted in triplicate and repeated three times. The interpretation of D-hLF 1-11 and anti-TB drug interaction is performed according to the prior publication [ 46 ]. The fractional inhibitory concentration (FIC) is defined as the lowest concentration of peptide and the anti-TB drug in combination that can inhibit the growth of M. tuberculosis divided by the MIC of either peptide or anti-TB drug.…”

Interaction of Selected Commercial Antiseptics with Natural Products against Methicillin-Resistant Staphylococcus aureus Strain

“…The results were interpreted as synergistic (FICI ≤ 0.5), additive (0.5 < FICI ≤ 1.0), no-effect (1.0 < FICI < 4.0) or antagonistic (FICI ≥ 4.0) [38].…”