Amphotericin B and Other Polyenes-Discovery, Clinical Use, Mode of Action and Drug Resistance

Area of Science:

• Mycology
• Pharmacology
• Infectious Diseases

Background:

• Polyenes, including amphotericin B, represent the oldest class of broad-spectrum antifungal agents.
• Despite their long history, polyenes are still considered the gold standard for treating numerous fungal infections.
• These antifungals possess broad-spectrum activity and fungicidal properties, with relatively rare resistance development.

Purpose of the Study:

• To review the historical context and clinical applications of polyene antifungal drugs.
• To explore the current understanding and ongoing debate surrounding the mode of action of polyenes.
• To summarize the diverse mechanisms of antifungal resistance to polyenes and emerging trends.

Main Methods:

• Literature review of historical and recent studies on polyene antifungals.
• Analysis of research on polyene mechanism of action and drug resistance.
• Examination of clinical data and emerging fungal pathogens, such as Candida auris.

Main Results:

• Polyenes exhibit broad-spectrum antifungal activity and fungicidal effects, but are associated with significant host toxicity.
• Recent research has revised the understanding of polyene mechanisms of action.
• New drug resistance mechanisms have been identified, with increasing concern over polyene-resistant fungal species.

Conclusions:

• Polyene antifungals remain vital therapeutic agents despite their toxicity.
• Understanding evolving resistance mechanisms is critical for effective antifungal therapy.
• Further research into polyene action and resistance is essential to combat emerging resistant fungal infections.