Current Role of Therapy with Amphotericin B

Abstract

Systemic antifungal chemotherapy frequently is more difficult to conduct than antibacterial therapy. Factors that make it difficult include, but are not limited to, common biosynthetic pathways among the eukaryotes and humans, a relative lack of agents, imprecise modes of use, general lack of standardization of in vitro susceptibility tests that have clinical correlations, and, with certain exceptions, lack of clinical correlations with in vitro results of combination antifungal chemotherapy. Amphotericin B has been available for intravenous administration for greater than 30 years and, despite its shortcomings, remains the drug of choice or reference agent in the therapy for many specific systemic fungal infections in various clinical settings. The current role of amphotericin B therapy in these situations and the need for additional controlled, comparative clinical trials with azoles, liposomal amphotericin B, and amphotericin B complex are discussed.

Heat Treatment of Amphotericin B Modifies Its Serum Pharmacokinetics, Tissue Distribution, and Renal Toxicity following Administration of a Single Intravenous Dose to Rabbits

“…The conventional AmpB-deoxycholate micellar formulation, Fungizone (FZ) (Bristol-Myers Squibb, Princeton, N.J.), has been used for over 45 years, and, despite its dose-dependent kidney toxicity, it remains the most widely used drug for the treatment of most systemic fungal infections (2,8,13). In addition, lesstoxic liposomal and lipid-associated AmpB formulations have been developed (e.g., AmBisome, Abelcet, and Amphocil), and, although they have been proven to reduce AmpB-induced kidney toxicity (6,(16)(17)(18)(19)(20), their use has been limited by their high expense.…”

A newly identified derivative of amphotericin B: isolation, structure determination and primary evaluation of the activity and toxicity

“…1,2 It was first isolated from Streptomyces nodosus in 1955 and has been used in the clinic since 1960 to treat a large variety of systemic fungal infections. 3,4 Amphotericin B is a macrocyclic lactone composed of a hydrophilic polyhydroxyl chain on one side and a lipophilic polyene hydrocarbon chain on the other side. Its molecular formula is C 47 H 73 NO 17 , and its chemical structure is shown in Figure 1.…”

Effect of Heat-Treated Amphotericin B on Renal and Fungal Cytotoxicity

“…For both FZ and HFZ, the concentration range which resulted in a 50% reduction of the growth of fungal cells was 0.125 to 1 mg/ml. These findings suggest that heat treatment decreases AMB's renal cytotoxicity without modifying its antifungal activity.Amphotericin B (AMB) is a polyene macrolide antibiotic used for the treatment of systemic fungal infections commonly found in immunocompromised patients (e.g., patients with AIDS), cancer patients, and diabetics (2,4,5,12,17,23). The conventional AMB-deoxycholate micellar formulation Fungizone (FZ; Bristol-Myers Squibb, Princeton, N.J.) has been used for over 45 years, and despite its dose-dependent kidney toxicity, it remains the most widely used drug for the treatment of most systemic fungal infections (2,12,17).…”

“…The conventional AMB-deoxycholate micellar formulation Fungizone (FZ; Bristol-Myers Squibb, Princeton, N.J.) has been used for over 45 years, and despite its dose-dependent kidney toxicity, it remains the most widely used drug for the treatment of most systemic fungal infections (2,12,17). In addition, less-toxic liposomal and lipid-associated AMB formulations have been developed (e.g., AmBisome, Abelcet, also known as AMB lipid complex [ABLC], and Amphocil), and although they have proved to reduce AMB-induced kidney toxicity (7,(20)(21)(22)(23)(24)(25), their use has been limited by their high expense.…”