Antifungal therapeutic drug monitoring: focus on drugs without a clear recommendation.
Clin Microbiol Infect. 2020 Jun 11;:
Authors: Gómez-López A
BACKGROUND: The goal of therapeutic drug monitoring is to determine the appropriate exposure of difficult-to-manage medications to optimize the clinical outcomes in patients under various clinical situations. Concerning antifungal treatment, and knowing that this procedure is expensive and time consuming, it is particularly recommended for certain systemic antifungals, i.e., agents with a well-defined exposure-response relationship and unpredictable pharmacokinetic profile or narrow therapeutic index. Little evidence supports the routine use of therapeutic drug monitoring for polyenes (amphotericin B), echinocandins, fluconazole or new azoles such as isavuconazole, despite the fact that a better understanding of antifungal exposure may lead to a better response.
OBJECTIVES: The aim of this work is to review published pharmacokinetic/pharmacodynamic data on systemically administered antifungals focusing on those whose monitoring is not routinely recommended by experts.
SOURCES: A MEDLINE search of the literature in English was performed introducing the following search terms "Amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, triazoles, caspofungin, micafungin, anidulafungin, echinocandins, pharmacokinetics, pharmacodynamics, and therapeutic drug monitoring. Review articles and guidelines were also screened.
CONTENT: This article collects different pharmacokinetic/pharmacodynamics aspects of systemic antifungals and summarizes recent threshold values for clinical outcomes and adverse events. Although for polyenes, echinocandins, fluconazole and isavuconazole extensive clinical validation is still required for a clear threshold and a routine monitoring recommendation, particular points such as liposome structure or complex pathophysiological conditions, affecting final exposure, are discussed. For the rest, their better-defined exposure-response/toxicity relationship allow to have useful threshold values and to justify routine monitoring. Additionally, clinical data are needed to better define thresholds that can minimise the development of antifungal resistance.
IMPLICATIONS: General therapeutic drug monitoring for all systemic antifungals is not recommended, however, this approach may help to stablish an adequate antifungal exposure for a favourable response, prevention of toxicity or development of resistance in special clinical circumstances.
PMID: 32535150 [PubMed - as supplied by publisher]