Antifungals: From Pharmacokinetics to Clinical Practice

Area of Science:

• Mycology
• Pharmacology
• Infectious Diseases

Background:

• Antifungal drug development began in the 1950s, with amphotericin B (AmB) as a key treatment for invasive fungal infections.
• Despite AmB's efficacy, severe side effects spurred the creation of azoles, echinocandins, and other drug classes, each with limitations like toxicity and emerging resistance.
• Rising incidence of invasive fungal infections, highlighted by the WHO's 2022 priority pathogens list, necessitates improved diagnostics, rational drug use, and novel therapeutic strategies.

Purpose of the Study:

• To provide a comprehensive historical overview and classification of antifungal drugs.
• To analyze the mechanisms of action, pharmacokinetics/pharmacodynamics (PK/PD), and clinical applications of existing and emerging antifungals.
• To explore the role of fungal biology, genetics, therapeutic drug monitoring, and pharmacogenomics in combating antifungal resistance and optimizing treatment outcomes.

Main Methods:

• Literature review and synthesis of historical data on antifungal drug development.
• Analysis of scientific literature on antifungal mechanisms, PK/PD, and clinical trial data.
• Examination of research on fungal resistance mechanisms and host-related factors influencing treatment efficacy.

Main Results:

• Detailed classification and historical progression of antifungal agents from polyenes to newer classes.
• Explanation of diverse mechanisms of action and PK/PD profiles influencing drug selection and dosing.
• Identification of key factors in antifungal resistance, including fungal genetics and host-specific responses.
• Highlighting the potential of therapeutic drug monitoring and pharmacogenomics for personalized antifungal therapy.

Conclusions:

• The evolution of antifungals reflects a continuous effort to balance efficacy with safety and overcome resistance.
• Understanding fungal biology and host factors is critical for developing effective strategies against invasive fungal infections.
• Personalized approaches, including therapeutic drug monitoring and pharmacogenomics, offer promising avenues to improve patient outcomes and mitigate antifungal resistance.