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Association between voriconazole exposure and Sequential Organ Failure Assessment (SOFA) score in critically ill patients.

Authors
  • Bienvenu, Anne-Lise1, 2
  • Pradat, Pierre3
  • Plesa, Alexandra1
  • Leclerc, Vincent1
  • Piriou, Vincent4
  • Fellahi, Jean-Luc5
  • Argaud, Laurent6
  • Rimmelé, Thomas7
  • Menotti, Jean8
  • Aubrun, Frédéric9
  • Richard, Jean-Christophe10
  • Gagnieu, Marie-Claude11
  • Parant, François11
  • Chidiac, Christian12
  • Leboucher, Gilles1
  • Tod, Michel1
  • Goutelle, Sylvain1, 13, 14
  • 1 Service Pharmacie, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France. , (France)
  • 2 ICBMS CNRS 5246, Campus Lyon-Tech La Doua, Université de Lyon, Lyon, France. , (France)
  • 3 Centre de Recherche Clinique, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France. , (France)
  • 4 Service d'anesthésie-réanimation, Groupement Hospitalier Sud, Hospices Civils de Lyon, Lyon, France. , (France)
  • 5 Service d'anesthésie-réanimation, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France. , (France)
  • 6 Service de réanimation médicale, Groupement Hospitalier Centre, Hospices Civils de Lyon, Lyon, France. , (France)
  • 7 Service d'anesthésie-réanimation, Groupement Hospitalier Centre, Hospices Civils de Lyon, Lyon, France. , (France)
  • 8 Service de Mycologie, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France. , (France)
  • 9 Service de réanimation chirurgicale, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France. , (France)
  • 10 Service de réanimation médicale, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France. , (France)
  • 11 Laboratoire de Biochimie et Biologie Moléculaire, UM Pharmaco-toxicologie Groupement Hospitalier Sud, Hospices Civils de Lyon, Lyon, France. , (France)
  • 12 Comité des Anti-Infectieux, Hospices Civils de Lyon, Lyon, France. , (France)
  • 13 Univ Lyon, Université Lyon 1, ISPB, Faculté de Pharmacie de Lyon, Lyon, France. , (France)
  • 14 Univ Lyon, Université Lyon 1 UMR CNRS 5558, Laboratoire de Biométrie et Biologie Evolutive, Villeurbanne, France. , (France)
Type
Published Article
Journal
PLoS ONE
Publisher
Public Library of Science
Publication Date
Jan 01, 2021
Volume
16
Issue
11
Identifiers
DOI: 10.1371/journal.pone.0260656
PMID: 34818379
Source
Medline
Language
English
License
Unknown

Abstract

Therapeutic drug monitoring (TDM) is essential for voriconazole to ensure optimal drug exposure, mainly in critically ill patients for whom voriconazole demonstrated a large variability. The study aimed at describing factors associated with trough voriconazole concentrations in critically ill patients and evaluating the impact of voriconazole concentrations on adverse effects. A 2-year retrospective multicenter cohort study (NCT04502771) was conducted in six intensive care units. Adult patients who had at least one voriconazole TDM were included. Univariable and multivariable linear regression analyses were performed to identify predictors of voriconazole concentrations, and univariable logistic regression analysis, to study the relationship between voriconazole concentrations and adverse effects. During the 2-year study period, 70 patients were included. Optimal trough voriconazole concentrations were reported in 37 patients (52.8%), subtherapeutic in 20 (28.6%), and supratherapeutic in 13 (18.6%). Adverse effects were reported in six (8.6%) patients. SOFA score was identified as a factor associated with an increase in voriconazole concentration (p = 0.025), mainly in the group of patients who had SOFA score ≥ 10. Moreover, an increase in voriconazole concentration was shown to be a risk factor for occurrence of adverse effects (p = 0.011). In that respect, critically ill patients who received voriconazole treatment must benefit from a TDM, particularly if they have a SOFA score ≥ 10. Indeed, identifying patients who are overdosed will help to prevent voriconazole related adverse effects. This result is of utmost importance given the recognized COVID-19-associated pulmonary aspergillosis in ICU patients for whom voriconazole is among the recommended first-line treatment.

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