Amphotericin B: A Comprehensive Pharmacological and Clinical Review

Introduction and Historical Context

Discovery and Enduring Legacy

Amphotericin B (AmB) represents one of the most significant milestones in the history of antimicrobial chemotherapy and stands as a foundational agent in the treatment of severe fungal diseases.[1] Its discovery in the 1950s marked the dawn of effective systemic antifungal therapy. The journey began with a broad screening program of actinomycete cultures, leading to the isolation of a potent antifungal compound from a strain of

Streptomyces nodosus.[1] This particular microorganism, originally identified as M-4575, was cultured from a soil sample collected in the Orinoco River region of Venezuela, a testament to the power of natural product screening in drug discovery.[1]

As a therapeutic agent, AmB was licensed in 1959 based on the available clinical data and became commercially accessible in 1960 under the trade name Fungizone® (Bristol-Myers-Squibb).[1] This initial formulation was a colloidal suspension of AmB complexed with the bile salt sodium deoxycholate, a necessary innovation to overcome the drug's inherent insolubility in water.[2] For decades following its introduction, AmB was the only reliable treatment for life-threatening systemic mycoses and quickly established itself as the "gold standard" against which all subsequent antifungals would be measured.[2] Even after more than 60 years and the development of newer antifungal classes like the azoles and echinocandins, AmB remains a first-line or indispensable second-line therapy for many of the most aggressive fungal infections, including cryptococcal meningitis, invasive mucormycosis, and severe forms of aspergillosis and candidiasis.[2] Its enduring relevance is rooted in its exceptionally broad spectrum of activity and a remarkably low incidence of acquired microbial resistance, a feature that sets it apart from nearly all other antimicrobial