Aspirin and verapamil increase the sensitivity of Candida albicans to caspofungin under planktonic and biofilm conditions

Abstract

Objectives: This study aimed to investigate the effects of caspofungin (CAS) combined with aspirin (ASP) or verapamil (VPL) on the sensitivity of Candida albicans under planktonic and biofilm conditions.

Methods: A total of 39 C. albicans clinical strains were used to construct biofilms. Sensitivity to ASP or VPL combined with CAS was analysed by broth microdilution. MIC₅₀ values were obtained and the fractional inhibitory concentration index (FICI) was calculated. Subsequently, C. albicans ZY22 was selected for time-growth curve analysis and strains ZY15 and ZY22 were used for time-kill curve analysis.

Results: Under planktonic condition the MIC₅₀ of CAS was 0.0313-8 μg/mL following treatment with CAS alone, whereas it decreased to 0.0313-4 μg/mL following CAS combined with ASP or VPL. Under biofilm condition the MIC₅₀ of CAS was 0.125-16 μg/mL following treatment with CAS alone, whereas it decreased to 0.0625-16 μg/mL or 0.0625-8 μg/mL following CAS combined with ASP or VPL. FICI results showed synergistic interactions between CAS and ASP under planktonic and biofilm conditions in 17 and 16 strains, respectively. However, synergistic interactions between CAS and VPL under planktonic and biofilm conditions were observed in 19 and 23 strains, respectively. Additionally, 8000 μg/mL ASP or 8 μg/mL VPL combined with CAS had better inhibitory effects on C. albicans.

Conclusion: ASP and VPL may be a sensitiser for CAS, and the antifungal effects of CAS may be sensitised by 8000 μg/mL ASP or 8 μg/mL VPL against C. albicans under planktonic and biofilm conditions.

Keywords: Aspirin; Biofilm; Candida albicans; Caspofungin; Planktonic; Verapamil.