Low isavuconazole trough levels in critically ill patients with and without extracorporeal membrane oxygenation

Data on isavuconazole exposure in critically ill patients and particularly during extracorporeal membrane oxygenation (ECMO) are scarce, and therapeutic drug monitoring is not routinely performed. Critically ill patients admitted to a tertiary ECMO referral center from October 2017 to August 2024 with documented isavuconazole trough levels were retrospectively analyzed. First, measured isavuconazole trough blood levels and the occurrence of dose adjustments were analyzed in patients with and without ECMO support. Fifty-three adult patients were included, of whom 11 (21%) patients were on ECMO support at the first isavuconazole trough level measurement. Median isavuconazole trough level was overall 1.4 (interquartile range [IQR] 0.9-2.5) mg/L and did not differ between ECMO (1.3 [IQR 0.9-1.5] mg/L) and non-ECMO patients (1.6 [IQR 0.9-2.8] mg/L, P = 0.423). During the entire intensive care unit stay, individual doses were increased in 12 (23%) patients, of whom 5 were on ECMO support, whereas dosage was reduced or interrupted in 2 (4%) patients (both without ECMO support). Dose adjustments occurred irregularly and inconsistently after therapeutic drug monitoring, i.e., only in 6 (11%) patients after the initial therapeutic drug monitoring despite 37 (70%) drug levels being outside the target range of 2-4 mg/L. In conclusion, below targeted isavuconazole trough levels were common in critically ill patients investigated, but ECMO did not seem to have an additional negative influence. Dose adjustments appeared more frequently than previously reported, albeit irregularly performed. Regular therapeutic drug monitoring and protocolized dose adjustments should be investigated in future studies.