Study on the antifungal effect of amphotericin B combined with fluconazole at different time points

Abstract

Objective To investigate the in vitro interaction of amphotericin B (AmB) and fluconazole (FLC) at different time points and provide a reference for clinical combined treatment therapy of polyenes and azoles. MethodsCandida albicans ATCC SC5314 was used in the study. The minimum inhibitory concentration (MIC) of antifungal drugs was determined using the double microdilution broth method. The same amount of DMSO and low concentration drugs were added to the DMSO treatment group at different time points (0, 2, 4, 6 h) to determine whether the solvent background environment affected the growth of Candida albicans. In the experimental group, to observe the effect of low concentration AmB on the antifungal effect of FLC, the experimental group was administered a low concentration of AmB (0.25 μg/mL or 0.125 μg/mL) added to FLC at different time points (0, 2, 4, 6 h), and the same amount of DMSO was added to FLC at different time points in the single drug control group. In the experimental group, to observe the effect of low concentration of FLC on the antifungal effect of AmB, the experimental group was administered a low concentration of FLC (0.06 μg/mL or 0.03 μg/mL) in AmB at different time points (0, 2, 4, 6 h), and the same amount of DMSO was used at different time points as the single drug control group. In the solvent group, the same amounts of DMSO and low concentration drugs were added at different time points. After resuscitation, the colony growth of each solvent control group, single-drug control group and experimental group was observed to evaluate the interaction between drug concentration and time. Compared with the AmB single-drug control group, there was no significant change in the experimental group with added low concentrations of FLC at 0 h (F=0.27, P=0.775), which was 1.74-1.93 times that of the control group at 2-4 h (P 0.05). Results Under the treatment of FLC at an inhibitory concentration (0.25 μg/ml), adding low concentration AMB did not affect the antifungal effect of FLC, and the multiple of colony count differences were not significant (P > 0.05). Conclusion The interaction between AmB and FLC was time-dependent. At the early stage (0 h), the interaction effect between fluconazole and amphotericin B was not clear. The fungicidal effect of AmB could be weakened when FLC was supplied at 2-4 h, and the effect of FLC on AmB was absent after 6 h.

Keywords

• candida albicans，
• amphotericin b，
• fluconazole，
• in vitro antifungal activity，
• minimal inhibitory concentration，
• drug combination，
• time-dependence，