Effect of butylated hydroxyanisole on the antifungal activity of amphotericin B

Monitoring the growth curves of Candida albicans has shown that in the presence of sub-MIC levels of amphotericin B the lag phase is extended. If butylated hydroxyanisole (BHA) is added prior to, or with the amphotericin B the lag phase is extended further. However, if BHA is added after the antibiotic, the growth curve is identical to that produced in the presence of amphotericin B alone. The effect of BHA was found to follow the kinetics of a zero order reaction, and adsorption data for amphotericin B to yeast cells shows that BHA may occupy sites in the cell wall of the organism normally occupied by amphotericin B. It is suggested that if the polyene binding capacity in the cell wall is satisfied by the BHA, then the effective concentration of amphotericin B available to exert its lethal effect on the sterol in the cell membrane is increased.