Amphotericin B

Abstract

Amphotericin B (AmB) has been the cornerstone of antifungal therapy for almost 50 years. Discovered in the late 1950s, it was approved for human use as an antifungal agent in 1960. Initial formulations of AmB were plagued with impurities. Allergic responses, presumably secondary to these impurities, and endotoxin-like infusion-related reactions were common. Although improvements in purification and fermentation over the last 30 years have enhanced tolerability, infusion-related reactions and renal dysfunction are still commonplace with the use of the deoxycholate solubilized formulation. Formulations using a lipid carrier have significantly improved tolerability. Safety aside, AmB remains the most effective, broad-spectrum, fungicidal agent with the greatest experience for the treatment of systemic mycoses. Both intrinsic and acquired resistance are limited. The treatment failures seen with AmB are multifaceted. These can be attributed to delays in diagnosis of invasive mycoses, the immune compromised state of the patient being treated, the unique pharmacokinetic/pharmacodynamic properties of the different formulations, and dose limitations related to toxicity. In an effort to enhance antifungal efficacy and reduce toxicity, AmB has been combined with other antifungals and new nonlipid formulations are being evaluated.