Observed Isavuconazole exposure: Five-year experience of azole TDM from a Spanish reference laboratory.

We aimed to assess patient exposure to isavuconazole from samples received in our laboratory for therapeutic antifungal monitoring. We used liquid chromatography coupled with ultraviolet absorbance detection adapted from a multiplex validated method with photodiode array 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 isavuconazole monitoring. The assay exhibited linearity between 0.25-16 mg/L for isavuconazole. 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 isavuconazole blood concentrations and compared them to those of voriconazole, posaconazole, and itraconazole for a period of five years (2017 to 2021). Median isavuconazole 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 reaches concentration values >2 mg/L. Different isavuconazole exposure between adults to children were found. In conclusion, isavuconazole achieves excellent blood concentrations compared to other azole drugs, they are almost identical to those previously described, they exceedthe MICs of most of 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, 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.