Suboptimal exposure to fluconazole in critically ill patients: Pharmacokinetic analysis and determinants - 03/12/22

Doi : 10.1016/j.idnow.2022.10.002

A.L. Bienvenu ^a,^b,^⁎ , P. Pradat ^c, E. Matusik ^a, V. Piriou ^d, T. Rimmelé ^e, F. Parant ^f, M. Tod ^a,^g,^h, G. Leboucher ^a, S. Goutelle ^a,^g,^h
on behalf of the
Antifungal study group
Florence Ader ⁱ, Laurent Argaud ^j, Frédéric Aubrun ^k, Jean-Luc Fellahi ^l, Céline Guichon ^k, Laurent Juillard ^m, Vincent Leclerc ⁿ, Charline Miossec ^o, Carole Paillet ^p, Alexandra Plesa ⁿ, Jean-Christophe Richard ^q, Sandrine Roux ⁱ, Florent Wallet ^r
ⁱ Maladies infectieuses, GHN, Hospices Civils de Lyon, Lyon, France
^j Réanimation médicale, GHC, Hospices Civils de Lyon, Lyon, France
^k Réanimation chirurgicale, GHN, Hospices Civils de Lyon, Lyon, France
^l Anesthésie-réanimation, GHE, Hospices Civils de Lyon, Lyon, France
^m Néphrologie, Hospices Civils de Lyon, Lyon, France
ⁿ Pharmacie, GHN, Hospices Civils de Lyon, France
^o Parasitologie et Mycologie, GHN, Hospices Civils de Lyon, Lyon, France
^p Pharmacie, GHC, Hospices Civils de Lyon, Lyon, France
^q Réanimation médicale, GHN, Hospices Civils de Lyon, Lyon, France
^r Anesthésie-réanimation, GHS, Hospices Civils de Lyon, Lyon, France

^a Service Pharmacie, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France
^b ICBMS CNRS 5246, Campus Lyon-Tech La Doua, Université de Lyon, Lyon, France
^c Centre de Recherche Clinique, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France
^d Service d’anesthésie-réanimation, Groupement Hospitalier Sud, Hospices Civils de Lyon, Lyon, France
^e Service d’anesthésie-réanimation, Groupement Hospitalier Centre, Hospices Civils de Lyon, Lyon, France
^f Laboratoire de Biochimie et Biologie Moléculaire, UM Pharmaco-toxicologie Groupement Hospitalier Sud, Hospices Civils de Lyon, Lyon, France
^g Univ Lyon, Université Lyon 1, ISPB, Faculté de Pharmacie de Lyon, Lyon, France
^h Univ Lyon, Université Lyon 1 UMR CNRS 5558, Laboratoire de Biométrie et Biologie Evolutive, Villeurbanne, France

^⁎Corresponding author at: Service Pharmacie, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.Service Pharmacie, Groupement Hospitalier Nord, Hospices Civils de LyonLyonFrance

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Saturday 03 December 2022
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Highlights

•	SOFA score ≥ 7 and GGT ≥ 100 associated with fluconazole underexposure.
•	A median loading dose of 890 mg (640–3450) needed to avoid underexposure.
•	Fluconazole therapeutic drug monitoring for critically ill patients.

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Abstract

Objectives

This study aims at evaluating fluconazole exposure in critically ill patients and identifying variables associated with the latter.

Patients and methods

This was a 2-year (2018–2019) retrospective multicenter cohort study. Adult patients > 18 years-old with at least one fluconazole concentration measurement during their ICU stay were included.

Results

Twenty patients were included. Only 11 patients had a fluconazole trough concentration (Cmin) within the target range (≥15 mg/L). According to bivariable analysis, SOFA score, GGT, fluconazole clearance, Ke, and Vd, were independently associated with a decrease in fluconazole Cmin. The median loading dose required to achieve the Cmin target appeared to be greater in patients with higher SOFA or GGT level and in patients undergoing renal replacement therapy.

Conclusions

This study supports recommendation for routine fluconazole therapeutic drug monitoring in ICU patients so as to avoid underexposure, especially if SOFA score is ≥ 7 and/or GGT is ≥ 100 U/L.

Le texte complet de cet article est disponible en PDF.

Keywords : Antifungal stewardship, Critically ill patients, Fluconazole, Pharmacokinetic, Therapeutic drug monitoring