Abstract
The optimization of antifungal therapy based on pharmacokinetics/pharmacodynamics (PK/PD) principles is crucial for improving outcomes in invasive fungal infections; however, its clinical application faces considerable hurdles. This review presents a comprehensive overview of current knowledge and aims to bridge basic research and clinical practice. We outline the fundamental concepts of PK/PD and the characteristics of the major antifungal drug classes (polyenes, echinocandins, flucytosines, and azoles), along with preclinical evidence defining the main PK/PD indices (maximum concentration to minimum inhibitory concentration ratio, 24-h area under the concentration-time curve to the minimum inhibitory concentration ratio, and percentage of time the concentration remains above the minimum inhibitory concentration). Key challenges hindering translation are critically analyzed, including substantial knowledge gaps—particularly for filamentous fungi; high inter-patient pharmacokinetic variability complicating standard dosing; limitations of therapeutic drug monitoring (TDM); the narrow therapeutic window requiring careful balance between efficacy and toxicity; and the role of suboptimal exposure in antifungal resistance. Current strategies, including antifungal stewardship, are discussed, and future directions highlighted. Prioritizing research on understudied pathogens, improving TDM, developing novel agents, and strengthening collaboration between basic research and clinical practice are essential. A deeper understanding and effective application of PK/PD principles are vital to advance personalized antifungal therapies and improve patient outcomes.
