Therapeutic Drug Monitoring of Antifungal Agents: Toward Harmonization of Therapeutic Ranges.
Abstract
Background
Invasive fungal infections are associated with high morbidity and mortality, particularly among immunocompromised and critically ill patients. Antifungal therapy is complicated by substantial pharmacokinetic variability, drug-drug interactions, and narrow therapeutic windows for some agents. Although therapeutic drug monitoring (TDM) can optimize drug exposure, therapeutic targets vary across studies and guidelines. The aim of this review was to provide an updated overview of antifungal TDM and support the harmonization of therapeutic ranges based on pharmacokinetic/pharmacodynamic (PK/PD) evidence.
Methods
A comprehensive search of major literature databases and international guidelines was conducted through November 2025 to identify studies reporting antifungal therapeutic targets and clinical applications of TDM. When therapeutic ranges differed across studies or guidelines, alternative targets were reported, considering the clinical settings and populations in which they were proposed.
Results
Robust evidence supports routine TDM for triazoles with high pharmacokinetic variability, particularly voriconazole and posaconazole, for which target trough concentrations are well established and associated with clinical outcomes. For isavuconazole, routine TDM is not universally recommended but may benefit selected high-risk populations, including critically ill, pediatric, and obese patients and those receiving extracorporeal therapies. Conversely, routine TDM is not currently recommended for echinocandins or amphotericin B because of limited exposure-response data, although emerging evidence suggests that TDM may be useful in selected clinical scenarios. Variability in PK/PD targets, analytical methods, and preanalytical factors contributes to inconsistent implementation in clinical practice.
Conclusions
Harmonization of antifungal therapeutic ranges is essential to improve the clinical utility of TDM and support individualized antifungal therapy. Further studies are required to establish standardized targets for all antifungal classes.