Isavuconazole Exposure in Critically Ill Patients Treated with Extracorporeal Membrane Oxygenation: Two Case Reports and a Narrative Literature Review

Abstract

Effective dosing of isavuconazole in patients supported by extracorporeal membrane oxygenation (ECMO) is important due to the role of isavuconazole as a first-line treatment in patients with influenza- and COVID-19-associated pulmonary aspergillosis. To date, robust pharmacokinetic data in patients supported by ECMO are limited. Therefore, it is unknown whether ECMO independently impacts isavuconazole exposure. We measured isavuconazole plasma concentrations in two patients supported by ECMO and estimated individual pharmacokinetic parameters using non-compartmental analysis and two previously published population pharmacokinetic models. Furthermore, a narrative literature review on isavuconazole exposure in adult patients receiving ECMO was performed. The 24 h areas under the concentration–time curve and trough concentrations of isavuconazole were lower in both patients compared with exposure values published before. In the literature, highly variable isavuconazole concentrations have been documented in patients with ECMO support. The independent effect of ECMO versus critical illness itself on isavuconazole exposure cannot be deduced from our and previously published (case) reports. Pending additional data, therapeutic drug monitoring is recommended in critically ill patients, regardless of ECMO support.

Antifungals in Patients With Extracorporeal Membrane Oxygenation: Clinical Implications

“…Recently, isavuconazole plasma concentration measurements in 7 critically ill patients with ECMO showed that isavuconazole was not altered by the ECMO oxygenator and that median plasma concentrations were >1 mg/L 24 hours after the first routine loading dose [ 25 ]. In 2 recently published cases, the 24-hour areas under the concentration–time curve and trough concentrations of isavuconazole were lower in both patients with ECMO in comparison with previously published data from non-ECMO patients [ 26 ]. Another case series including 9 critically ill patients with IFD and ECMO revealed that isavuconazole plasma levels were lower in patients receiving ECMO therapy compared with patients without ECMO [ 27 ].…”

Isavuconazole Pharmacokinetics in Critically Ill Patients: Relationship with Clinical Effectiveness and Patient Safety

“…Nevertheless, extrapolating these conclusions to critically ill patient could be inaccurate. The limited number of studies on isavuconazole Pk in critical care patients has shown inconsistent results [12][13][14]. Impaired renal or hepatic function, continuous renal replacement therapy (CRRT) or extracorporeal membrane oxygenation (ECMO) make drug concentrations prediction di cult, and thus, TDM could be necessary in this population [15][16][17][18][19].…”