Navigating Therapeutic drug monitoring of Isavuconazole in Invasive Mold Infection on Extracorporeal membrane oxygenation - A Case Report.

Abstract

Background: Isavuconazole is an azole antifungal with extended activity against yeast and molds. It is highly lipophilic, largely protein bound, and has a large volume of distribution. Critically ill patients exhibit altered pharmacokinetics (PK) of antimicrobials due to physiologic changes and other organ support modalities, including extracorporeal membrane oxygenation (ECMO). Azole antifungals, including isavuconazole, are prone to significant reduction in serum concentrations during ECMO support as a result of sequestration in the circuit and mechanical destruction of the drug via centrifugal pump, often necessitating therapeutic drug monitoring (TDM). Herein, we report a case of a young male treated for suspected invasive pulmonary aspergillosis who was placed on ECMO and treated with isavuconazole. Despite escalating doses and intense TDM, therapeutic concentrations were unable to be achieved. The patient was switched to voriconazole and liposomal amphotericin B. The patient achieved clinical improvement and switched back to isavuconazole to complete a 12-week course after ECMO decannulation occurred. This case highlights the importance of isavuconazole TDM, especially during ECMO, and consideration of alternative agents if necessary.