Sixty years of Amphotericin B: An Overview of the Main Antifungal Agent Used to Treat Invasive Fungal Infections

Abstract

Introduced in the late 1950s, polyenes represent the oldest family of antifungal drugs. The discovery of amphotericin B and its therapeutic uses is considered one of the most important scientific milestones of the twentieth century . Despite its toxic potential, it remains useful in the treatment of invasive fungal diseases owing to its broad spectrum of activity, low resistance rate, and excellent clinical and pharmacological action. The well-reported and defined toxicity of the conventional drug has meant that much attention has been paid to the development of new products that could minimize this effect. As a result, lipid-based formulations of amphotericin B have emerged and, even keeping the active principle in common, present distinct characteristics that may influence therapeutic results. This study presents an overview of the pharmacological properties of the different formulations for systemic use of amphotericin B available for the treatment of invasive fungal infections, highlighting the characteristics related to their chemical, pharmacokinetic structures, drug–target interactions, stability, and others, and points out the most relevant aspects for clinical practice.

Quest for the Molecular Basis of Improved Selective Toxicity of All-Trans Isomers of Aromatic Heptaene Macrolide Antifungal Antibiotics

“…They are characterized by a large macrocyclic lactone ring (macronolide) containing a system of 3–7 conjugated double bonds and a number of hydrophilic substituents, including a glycosidically bound aminosugar, most often D-mycosamine (3,6-dideoxy-3-amino- d -mannose) [ 1 ]. The most interesting and prospective group of polyene macrolides are the heptaenes, with Amphotericin B (AmB) still being considered as ‘the lifesaving drug’ and ‘the golden standard’ for antifungal agents [ 2 ]. Heptaenes fall into two major categories: non-aromatic heptaenes (including AmB) and aromatic heptaene macrolides (AHMs).…”

Polyhydroxyalkanoate/Antifungal Polyene Formulations with Monomeric Hydroxyalkanoic Acids for Improved Antifungal Efficiency

“…Introduced in 1950s, polyenes represent the oldest family of antifungal drugs [ 31 , 32 ]. Despite their potential toxicity, polyenes remain useful in the treatment of invasive fungal infections because of their broad-spectrum activity, low rates of resistance and established clinical record, particularly in immunocompromised patients.…”

“…While different formulations of nystatin have been developed [ 36 ], the topical formulation of nystatin remains the most widespread in clinical use [ 37 ]. Amphotericin B deoxycholate has been the “gold standard” treatment for invasive fungal infections for over 50 years [ 31 , 38 , 39 ]. Driven to improve on the renal toxicity of amphotericin B deoxycholate, extensive pharmaceutical research has led to the development of several new amphotericin B formulations.…”

Antifungal macrocycle antibiotic amphotericin B — its present and future. Multidisciplinary perspective for the use in the medical practice

“…Очень эффективно лечение амфотерицином В офтальмомикозов грибковой этиологии, таких как кератиты, вызванные нитчатыми грибами [16][17][18][19], а также грибковые заболевания, вызываемые Candida, Aspergillus, Fusarium, Cryptococcus, Mucorales, Scedosporium, Paecilomyces [20,21]. Хотелось бы отметить его особую роль (преимущественно при лечении липид-ассоциированными формами амфотерицина В) при лёгочных микозах, особенно при аспергиллёзе, который является причиной 30% летальных исходов аспергиллёзных пациентов, заражённых коронавирусом, что особенно актуально в период пандемии [22][23][24][25]. Лечение амфотерицином В весьма эффективно также при инвазивных микозах, таких как гистоплазмоз, бластомикоз и грибковый менингит, которые имеют локальные очаги инфекции [22,26].…”

“…Хотелось бы отметить его особую роль (преимущественно при лечении липид-ассоциированными формами амфотерицина В) при лёгочных микозах, особенно при аспергиллёзе, который является причиной 30% летальных исходов аспергиллёзных пациентов, заражённых коронавирусом, что особенно актуально в период пандемии [22][23][24][25]. Лечение амфотерицином В весьма эффективно также при инвазивных микозах, таких как гистоплазмоз, бластомикоз и грибковый менингит, которые имеют локальные очаги инфекции [22,26]. [3,4,22,[30][31][32].…”