Therapeutic Drug Monitoring of Antifungal Agents in Clinical Practice

Therapeutic drug monitoring (TDM) of antifungal agents has emerged as a critical component in the management of invasive fungal infections. Wide interindividual variability in absorption, distribution, metabolism and elimination of triazoles, echinocandins and polyenes can result in subtherapeutic exposure or toxic concentrations. Monitoring plasma levels enables clinicians to tailor dosing, optimise efficacy and minimise adverse events. Integration of pharmacogenetic factors, such as CYP2C19 polymorphisms affecting voriconazole metabolism, and the influence of critical illness, inflammation and extracorporeal devices on drug disposition has refined TDM strategies. Advances in bioanalytical methods now permit simultaneous quantification of multiple agents from small serum volumes, facilitating rapid dose adjustment in diverse clinical settings. Ultimately, incorporation of TDM into antifungal stewardship offers a personalised approach that improves global outcomes in high-risk populations.

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Therapeutic Drug Monitoring of Antifungal Agents in Clinical Practice publication trend

The graph below shows the total number of articles in therapeutic drug monitoring of antifungal agents in clinical practice across all publications each year (not limited to Nature Index journals).

Technical terms

Therapeutic drug monitoring (TDM): Measurement of drug concentrations at designated intervals to maintain a constant therapeutic range.

Pharmacokinetics (PK): Study of drug absorption, distribution, metabolism and excretion over time.

Trough concentration: Lowest drug level in plasma, typically measured immediately before the next dose.

Area under the concentration–time curve (AUC): Integral of plasma drug concentration over time, reflecting overall exposure.

Minimum inhibitory concentration (MIC): Lowest drug concentration that prevents visible growth of a fungal pathogen in vitro.

CYP2C19 polymorphism: Genetic variation in the liver enzyme that influences metabolism of triazole antifungals.

Extracorporeal membrane oxygenation (ECMO): Life-support technique that can alter drug clearance by external circulation and oxygenation.

References

1. Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections. Pharmaceutics (2023).
2. Establishment of a mathematical prediction model for voriconazole stable maintenance dose: a prospective study. Frontiers in Cellular and Infection Microbiology (2023).
3. Simultaneous Quantification of Seven Antifungal Agents in Human Serum Using Liquid Chromatography-Tandem Mass Spectrometry. Pharmaceuticals (2023).
4. Isavuconazole Exposure in Critically Ill Patients Treated with Extracorporeal Membrane Oxygenation: Two Case Reports and a Narrative Literature Review. Antibiotics (2023).