In vitro synergy of azole antifungals and methotrexate against Candida albicans

Objective: This study aims to evaluate the effective of azoles and MTX for patients with invasive candidiasis. Methods: We used the disk diffusion assay and the checkerboard assay to evaluate the in vitro interactions between MTX and antifungals. In addition, we used the transmission electron microscopy to observe the ultrastructure of the effect of MTX and fluconazole on Candida albicans. Results: The rates of synergy for the combination of MTX with fluconazole (FLC), itraconazole (ITC), and voriconazole (VRZ) were 91.3%, 65.2%, and 87% in checkerboard testing. No antagonism was found between methotrexate and azole antifungals in any of the strains. Furthermore, MTX treated C. albicans showed extensive cell wall vacuolations and the inhibition of blastospores growth, as observed using transmission electron microscopy. There was an apparent destruction of the cell membrane and cell wall resulting in the destruction of cytoplasm, a phenomenon observed when MTX was combined with azoles. Conclusion: This study provides evidence that the combination of azoles and MTX is effective for patients with invasive candidiasis, which on the other hand, will reduce the side effects of the drugs.