A Large Retrospective Assessment of Voriconazole Exposure in Patients Treated with Extracorporeal Membrane Oxygenation.

Autor:	Van Daele R; Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.; Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium., Bekkers B; Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium., Lindfors M; ECMO Centre Karolinska, Department of Pediatric Perioperative Medicine and Intensive Care, Karolinska University Hospital, 17177 Stockholm, Sweden.; Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden., Broman LM; ECMO Centre Karolinska, Department of Pediatric Perioperative Medicine and Intensive Care, Karolinska University Hospital, 17177 Stockholm, Sweden.; Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden., Schauwvlieghe A; Department of Hematology, Ghent University Hospital, 9000 Ghent, Belgium.; Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, 3015 CP Rotterdam, The Netherlands., Rijnders B; Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, 3015 CP Rotterdam, The Netherlands.; Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, 3015 CP Rotterdam, The Netherlands., Hunfeld NGM; Department of Intensive Care and Department of Hospital Pharmacy, Erasmus University Medical Center, 3015 CP Rotterdam, The Netherlands., Juffermans NP; Department of Intensive Care, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands., Taccone FS; Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles (ULB), 1050 Brussels, Belgium., Coimbra Sousa CA; Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles (ULB), 1050 Brussels, Belgium., Jacquet LM; Cardiovascular Intensive Care, Cliniques Universitaires Saint-Luc, 1050 Brussels, Belgium., Laterre PF; Department of Intensive Care, Cliniques Universitaires St-Luc, Université Catholique de Louvain, 1050 Brussels, Belgium., Nulens E; Laboratory Medicine, Medical Microbiology, Algemeen Ziekenhuis Sint-Jan, Brugge-Oostende, 8000 Brugge, Belgium., Grootaert V; Pharmacy Department, Algemeen Ziekenhuis Sint-Jan Brugge-Oostende AV, 8000 Brugge, Belgium., Lyster H; Pharmacy Department, Royal Brompton & Harefield Hospitals, London SW3 6NP, UK.; Cardiothoracic Transplant Unit, Royal Brompton & Harefield Hospitals, London SW3 6NP, UK., Reed A; Cardiothoracic Transplant Unit, Royal Brompton & Harefield Hospitals, London SW3 6NP, UK.; Imperial College London, London SW3 6NP, UK., Patel B; Division of Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery & Cancer, Faculty of Medicine, Imperial College, London SW3 6NP, UK.; Department of Adult Intensive Care, The Royal Brompton and Harefield Hospitals, London SW3 6NP, UK., Meersseman P; Department of General Internal Medicine, Medical Intensive Care Unit, University Hospitals Leuven, 3000 Leuven, Belgium., Debaveye Y; Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.; Intensive Care Unit, University Hospitals Leuven, 3000 Leuven, Belgium., Wauters J; Department of Microbiology and Immunology, KU Leuven, 3000 Leuven, Belgium.; Medical Intensive Care Unit, University Hospitals Leuven, 3000 Leuven, Belgium., Vandenbriele C; Department of Adult Intensive Care, The Royal Brompton and Harefield Hospitals, London SW3 6NP, UK.; Department of Cardiovascular Sciences, KU Leuven, 3000 Leuven, Belgium.; Department of Cardiovascular Diseases, University Hospitals Leuven, 3000 Leuven, Belgium., Spriet I; Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.; Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium.
Jazyk:	angličtina
Zdroj:	Microorganisms [Microorganisms] 2021 Jul 20; Vol. 9 (7). Date of Electronic Publication: 2021 Jul 20.
DOI:	10.3390/microorganisms9071543
Abstrakt:	Background: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population. Methods: Critically ill patients from eight centers in four countries treated with voriconazole during ECMO support were included in this retrospective study. Voriconazole concentrations were collected in a period on ECMO and before/after ECMO treatment. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure and to assess the impact of possible saturation of the circuit's binding sites over time. Results: Sixty-nine patients and 337 samples (190 during and 147 before/after ECMO) were analyzed. Subtherapeutic concentrations (<2 mg/L) were observed in 56% of the samples during ECMO and 39% without ECMO ( p = 0.80). The median trough concentration, for a similar daily dose, was 2.4 (1.2-4.7) mg/L under ECMO and 2.5 (1.4-3.9) mg/L without ECMO ( p = 0.58). Extensive inter-and intrasubject variability were observed. Neither ECMO nor squared day of ECMO (saturation) were retained as significant covariates on voriconazole exposure. Conclusions: No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations.
Databáze:	MEDLINE
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