Affiliation:
1. Mycology Reference and Research Laboratory (National Centre for Microbiology CNM-ISCIII) , Instituto de Salud Carlos III Carretera Majadahonda-Pozuelo Km 2 28220 Madrid , Spain
2. Center for Biomedical Research in Network in Infectious Diseases (CIBERINFEC-CB21/13/00105) , Instituto de Salud Carlos III. Carretera Majadahonda-Pozuelo Km 2 Madrid , Spain
Abstract
Abstract
We aimed to assess patient exposure to isavuconazole (ISZ) from samples received in our laboratory for therapeutic antifungal monitoring. We used liquid chromatography coupled with ultraviolet (UV) absorbance detection adapted from a multiplex-validated method with photodiode array (PDA) detection to monitor the analytes. The latter device allows the characterization of the azoles UV spectra. The method was validated according to international guidelines for efficient ISZ monitoring.
The assay exhibited linearity between 0.25 and 16 mg/l for ISZ. Accuracy and intra- and inter-day precision were within acceptable ranges, and the method was successfully applied to quantify azoles and major metabolites from clinical samples collected from treated patients. We focus on ISZ blood concentrations and compared them to those of voriconazole, posaconazole, and itraconazole for a period of 5 years (2017–2021). Median ISZ concentration was 2.92 mg/l (interquartile range 1.82–5.33 mg/l) with 89% of measurements classified as adequate exposure (> 1 mg/l). Additionally, 71% of samples reach concentration values > 2 mg/l. Different ISZ exposure between adults to children were found.
In conclusion, ISZ achieves excellent blood concentrations compared to other azole drugs, they are almost identical to those previously described, they exceed the MICs of most fungi for which its use was recommended and they differ depending on the patient’s age. The method we describe for antifungal monitoring is simple, robust, and efficient. It simultaneously analyzes azoles and metabolites, and can be used for tailored interventions, achieve exposures associated with therapeutic success, decrease treatment-related toxicity, and help prevent resistance emergence due to continuous azole sub-optimal concentrations.
Funder
Instituto de Salud Carlos III
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,General Medicine
Cited by
1 articles.
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