Isavuconazole Exposure in Critically Ill Patients Treated with Extracorporeal Membrane Oxygenation: Two Case Reports and a Narrative Literature Review
Beatrijs Mertens,
Omar Elkayal,
Erwin Dreesen,
Joost Wauters,
Philippe Meersseman,
Yves Debaveye,
Karlien Degezelle,
Pieter Vermeersch,
Matthias Gijsen,
Isabel Spriet
Affiliations
Beatrijs Mertens
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven and Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium
Omar Elkayal
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium
Erwin Dreesen
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium
Joost Wauters
Department of Microbiology, Immunology and Transplantation, KU Leuven and Medical Intensive Care Unit, University Hospitals Leuven, 3000 Leuven, Belgium
Philippe Meersseman
Department of Microbiology, Immunology and Transplantation, KU Leuven and Medical Intensive Care Unit, University Hospitals Leuven, 3000 Leuven, Belgium
Yves Debaveye
Department of Cellular and Molecular Medicine, KU Leuven and Intensive Care Unit, University Hospitals Leuven, 3000 Leuven, Belgium
Karlien Degezelle
Department of Perfusion Technology, University Hospitals Leuven, 3000 Leuven, Belgium
Pieter Vermeersch
Clinical Department of Laboratory Medicine, University Hospitals Leuven, 3000 Leuven, Belgium
Matthias Gijsen
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven and Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium
Isabel Spriet
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven and Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium
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.
