Therapeutic drug monitoring of antifungal therapies: do we really need it and what are the best practices?

ABSTRACT

Introduction

Despite advancements, invasive fungal infections (IFI) still carry high mortality rates, often exceeding 30%. The challenges in diagnosis, coupled with limited effective antifungal options, make managing IFIs complex. Antifungal drugs are essential for IFI management, but their efficacy can be diminished by drug–drug interactions and pharmacokinetic variability. Therapeutic Drug Monitoring (TDM), especially in the context of triazole use, has emerged as a valuable strategy to optimize antifungal therapy.

Areas covered

This review provides current evidence regarding the potential benefits of TDM in IFI management. It discusses how TDM can enhance treatment response, safety, and address altered pharmacokinetics in specific patient populations.

Expert opinion

TDM plays a crucial role in achieving optimal therapeutic outcomes in IFI management, particularly for certain antifungal agents. Preclinical studies consistently show a link between therapeutic drug levels and antifungal efficacy. However, clinical research in mycology faces challenges due to patient heterogeneity and the diversity of fungal infections. TDM’s potential advantages in guiding Echinocandin therapy for critically ill patients warrant further investigation. Additionally, for drugs like Posaconazole, assessing whether serum levels or alternative markers like saliva offer the best measure of efficacy is an intriguing question.

KEYWORDS:

• TDM
• Therapeutic drug monitoring
• invasive fungal infection
• echinocandin
• posaconazole
• isavuconazole
• antifungals

Article highlights

• TDM plays a crucial role in achieving optimal therapeutic outcomes.

• Preclinical studies consistently show a link between therapeutic drug levels and antifungal efficacy.

• TDM of echinocandins might be useful in specific patient populations (e.g., obese, critically ill).

• Parameters other than serum concentrations, like saliva levels may aid in the guidance of antifungal therapy.

• Further investigations are required to establish clear cutoff concentrations for clinical utility.

Declaration of interest

M Hoenigl received research funding from Gilead, Astellas, MSD, Euroimmune, IMMY, Mundipharma, Scynexis, Pulmocide, F2G and Pfizer, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.