Amphotericin B and Other Polyenic Antifungal Antibiotics

Abstract

The polyenic antifungal antibiotics are a large group of related macrolides whose ring contains a rigid planar lipophilic portion and a flexible hydrophilic portion. These inhibit growth of fungi (but not of bacteria) and have significant value in treatment of intestinal or topical monilial infections. Amphotericin B is used systemically for the treatment of acute histoplasmosis and blastomycosis. After the initial demonstration of therapeutic utility, attention became focused on the in vitro biologic action of the polyenes. The critical step was identified as formation of a complex with the membrane sterol of sensitive organisms. The consequences of this binding are being examined using natural and artificial membranes. The surprising feature that has emerged is the wide variation in ultimate physiologic effects produced by the individual polyenes. Investigation of this problem should provide important information on membrane function as well as on the nature of the specific membrane complexes. Finally, and of great interest at the moment, physiologic and pharmacologic effects on sterol and steroid metabolism in animals have been observed. These changes are consistent with available information on the mechanism of the microbial action of the polyenes. The possible practical application of these discoveries is of great interest.