In vitro synergistic effect of tetrandrine on ketoconazole against Candida parapsilosis complex

Objective To evaluate the in vitro synergistic effect of tetrandrine on ketoconazole against Candida parapsilosis complex. Methods According to the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines, the microdilution checkerboard method was used to evaluate in vitro antifungal activities of ketoconazole alone and in combination with tetrandrine against 21 clinical isolates of Candida parapsilosis complex based on the fractional inhibitory concentration index (FICI) . Antifungal effects of the above drugs at different time points were evaluated by the XTT assay, and then time-killing curves were drawn and assessed to investigate the in vitro dynamic antifungal activity. Results The minimum inhibitory concentrations (MICs) of tetrandrine and ketoconazole alone against 21 clinical isolates of Candida parapsilosis complex were 32-64 mg/L and 0.031 25-2 mg/L, respectively. When ketoconazole was combined with tetrandrine, MICs of tetrandrine and ketoconazole were reduced to 2-8 mg/L and 0.008-0.25 mg/L respectively, and the FICI ranged from 0.09 to 0.5. The time-killing curves revealed that the fungal growth was delayed obviously in the combination group compared with the ketoconazole alone group and tetrandrine alone group. Conclusion Tetrandrine has obvious synergistic effects on ketoconazole against Candida parapsilosis complex in vitro. Key words: Candida; Ketoconazole; Tetrandrine; Drug synergism; Candida parapsilosis complex