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

critically ill patients exposure extracorporeal membrane oxygenation invasive fungal infections pharmacokinetics therapeutic drug monitoring variability voriconazole

Journal

Microorganisms
ISSN: 2076-2607
Titre abrégé: Microorganisms
Pays: Switzerland
ID NLM: 101625893

Informations de publication

Date de publication:
20 Jul 2021
Historique:
received: 31 05 2021
revised: 12 07 2021
accepted: 14 07 2021
entrez: 7 8 2021
pubmed: 8 8 2021
medline: 8 8 2021
Statut: epublish

Résumé

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. 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. 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 ( No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations.

Sections du résumé

BACKGROUND 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 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 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 (
CONCLUSIONS CONCLUSIONS
No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations.

Identifiants

pubmed: 34361978
pii: microorganisms9071543
doi: 10.3390/microorganisms9071543
pmc: PMC8303158
pii:
doi:

Types de publication

Journal Article

Langues

eng

Références

Intensive Care Med. 2007 Jun;33(6):1018-24
pubmed: 17404709
Drug Metab Rev. 2019 Aug;51(3):247-265
pubmed: 31215810
Intensive Care Med. 2009 Jan;35(1):183-4
pubmed: 18795256
ASAIO J. 2021 Mar 29;:
pubmed: 33788798
J Fungi (Basel). 2020 Jun 22;6(2):
pubmed: 32580296
Basic Clin Pharmacol Toxicol. 2020 Dec;127(6):495-504
pubmed: 32639669
Crit Care. 2018 Apr 17;22(1):98
pubmed: 29665838
Lancet. 2021 Feb 6;397(10273):499-509
pubmed: 33549194
Transpl Infect Dis. 2021 Jun;23(3):e13545
pubmed: 33316840
J Fungi (Basel). 2020 Jun 24;6(2):
pubmed: 32599813
Int J Antimicrob Agents. 2010 May;35(5):468-72
pubmed: 20188523
J Transl Med. 2020 May 27;18(1):213
pubmed: 32460856
Antimicrob Agents Chemother. 2013 Jul;57(7):3262-7
pubmed: 23629724
Front Pediatr. 2020 Aug 27;8:468
pubmed: 32974242
J Antimicrob Chemother. 2014 May;69(5):1162-76
pubmed: 24379304
J Antimicrob Chemother. 2021 Apr 13;76(5):1234-1241
pubmed: 33517360
Ann Clin Microbiol Antimicrob. 2017 Sep 11;16(1):60
pubmed: 28893246
Crit Care. 2018 Dec 22;22(1):355
pubmed: 30577863
J Antimicrob Chemother. 2009 Apr;63(4):767-70
pubmed: 19218271
J Clin Pharm Ther. 2019 Aug;44(4):572-578
pubmed: 30851209
Perfusion. 2020 Sep;35(6):529-533
pubmed: 32627659
J Clin Pharm Ther. 2017 Dec;42(6):661-671
pubmed: 28948652
Intensive Care Med. 2012 Nov;38(11):1761-8
pubmed: 22895826
Clin Infect Dis. 2016 Aug 15;63(4):e1-e60
pubmed: 27365388
Int J Environ Res Public Health. 2021 Jan 28;18(3):
pubmed: 33525739
Am J Health Syst Pharm. 2016 Mar 1;73(5 Suppl 1):S14-21
pubmed: 26896521
J Antimicrob Chemother. 2017 Mar 1;72(suppl_1):i39-i47
pubmed: 28355466
Clin Microbiol Infect. 2013 Dec;19(12):1115-21
pubmed: 24118188
ASAIO J. 2003 Jan-Feb;49(1):41-7
pubmed: 12558306
J Antimicrob Chemother. 2019 Mar 1;74(3):761-767
pubmed: 30476108
Crit Care. 2015 Jan 12;19:7
pubmed: 25928694
Curr Opin Crit Care. 2015 Oct;21(5):421-9
pubmed: 26165502
Ther Drug Monit. 2008 Feb;30(1):117-9
pubmed: 18223474
Pharmacotherapy. 2020 Jan;40(1):89-95
pubmed: 31742741
Ther Drug Monit. 2008 Dec;30(6):643-6
pubmed: 19057370
Lancet. 2016 Feb 20;387(10020):760-9
pubmed: 26684607

Auteurs

Ruth Van Daele (R)

Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.
Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium.

Britt Bekkers (B)

Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium.

Mattias 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.

Lars Mikael 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.

Alexander 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.

Bart 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.

Nicole G M Hunfeld (NGM)

Department of Intensive Care and Department of Hospital Pharmacy, Erasmus University Medical Center, 3015 CP Rotterdam, The Netherlands.

Nicole P Juffermans (NP)

Department of Intensive Care, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands.

Fabio Silvio Taccone (FS)

Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles (ULB), 1050 Brussels, Belgium.

Carlos Antônio Coimbra Sousa (CA)

Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles (ULB), 1050 Brussels, Belgium.

Luc-Marie Jacquet (LM)

Cardiovascular Intensive Care, Cliniques Universitaires Saint-Luc, 1050 Brussels, Belgium.

Pierre-François Laterre (PF)

Department of Intensive Care, Cliniques Universitaires St-Luc, Université Catholique de Louvain, 1050 Brussels, Belgium.

Eric Nulens (E)

Laboratory Medicine, Medical Microbiology, Algemeen Ziekenhuis Sint-Jan, Brugge-Oostende, 8000 Brugge, Belgium.

Veerle Grootaert (V)

Pharmacy Department, Algemeen Ziekenhuis Sint-Jan Brugge-Oostende AV, 8000 Brugge, Belgium.

Haifa Lyster (H)

Pharmacy Department, Royal Brompton & Harefield Hospitals, London SW3 6NP, UK.
Cardiothoracic Transplant Unit, Royal Brompton & Harefield Hospitals, London SW3 6NP, UK.

Anna Reed (A)

Cardiothoracic Transplant Unit, Royal Brompton & Harefield Hospitals, London SW3 6NP, UK.
Imperial College London, London SW3 6NP, UK.

Brijesh 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.

Philippe Meersseman (P)

Department of General Internal Medicine, Medical Intensive Care Unit, University Hospitals Leuven, 3000 Leuven, Belgium.

Yves Debaveye (Y)

Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.
Intensive Care Unit, University Hospitals Leuven, 3000 Leuven, Belgium.

Joost Wauters (J)

Department of Microbiology and Immunology, KU Leuven, 3000 Leuven, Belgium.
Medical Intensive Care Unit, University Hospitals Leuven, 3000 Leuven, Belgium.

Christophe 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.

Isabel Spriet (I)

Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.
Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium.

Classifications MeSH