Disclosure(s): No relevant financial relationship(s) to disclose.
Introduction: Due to the favorable pharmacokinetic characteristics of isavuconazole, TDM is not required based on the SECURE trial. However, interindividual variability and subtherapeutic levels have been scarcely reported in the critically ill population, who are known to have significantly altered pharmacokinetics. We conducted this analysis to gather more data on this population.
Methods: This is a retrospective, single-center study. Adults (≥ 20 yo) at ICU of a tertiary academic medical center who had isavuconazole levels between 10/2023 and 7/2025 were included. Levels that reflected separate isavuconazole treatment courses were allowed, but those drawn after dose modification based on the previous TDM results were excluded.
Results: A total of 26 patients with 28 samples were eligible for the analysis. Male 73%, median 58 years (IQR 47.8-68), median BW 58 kg (51.8-63.3), and a median BMI 21 (19.9-23.5) on the day of TDM. Malignant hematology 61.5%, oncology 26.9%, rheumatology 23%, and organ transplant 7.6%. All patients received a standard isavuconazole regimen, except for 3 patients. Median SOFA score 13.5 (8-15.25) on the day of TDM. 57.1% hyperbilirubinemia and 7.6% liver cirrhosis, but only 9% developed acute liver failure. 2 patients were on ECMO.
The levels were drawn at a median of 10 days in 23 samples, after excluding 5 samples that were collected after chronic (>21 days) use. Median level 2.94, and 60.7% were within the therapeutic range (2-5 mg/L). 26% of levels were drawn earlier than day 7, with a median of 4.5 days and 2.05 mg/L. 21.4% supratherapeutic levels. The individuals who had liver cirrhosis both had supratherapeutic levels. Subtherapeutic levels 17.8%, and 7.1% < 1 mg/L. Two of the subtherapeutic levels were drawn during DDI with rifabutin.
Discussion Unlike subtherapeutic isavuconazole levels in critically ill patients reported before, the therapeutic target of isavuconazole was met in our cohort. The most significant difference is that our patients had a lower BMI < 25.
Although our patients reached the isavuconazole therapeutic target, only 60.7% remained in the therapeutic range.
Conclusions: Isavuconazole TDM in the critically ill population is warranted, especially when liver cirrhosis or DDI is present.
