Factors influencing voriconazole plasma level in intensive care patients

Christopher Alexander Hinze; Jan Fuge; Denis Grote-Koska; Korbinian Brand; Hortense Slevogt; Markus Cornberg; Susanne Simon; Oana Joean; Tobias Welte; Jessica Rademacher

doi:10.1093/jacamr/dlae045

Factors influencing voriconazole plasma level in intensive care patients

JAC Antimicrob Resist. 2024 Mar 18;6(2):dlae045. doi: 10.1093/jacamr/dlae045. eCollection 2024 Apr.

Authors

Christopher Alexander Hinze¹, Jan Fuge², Denis Grote-Koska³, Korbinian Brand³, Hortense Slevogt^{1

2

4}, Markus Cornberg^{5

6}, Susanne Simon¹, Oana Joean¹, Tobias Welte^{1

2}, Jessica Rademacher^{1

2}

Affiliations

¹ Department of Respiratory Medicine and Infectious Disease, Hannover Medical School, Hannover, Germany.
² Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany.
³ Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany.
⁴ Respiratory Infection Dynamics Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
⁵ Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Centre for Individualized Infection Medicine, Hannover, Germany.
⁶ German Center for Infection Research (DZIF), partner-site Hannover-Braunschweig, Hannover, Germany.

Abstract

Background: In clinical routine, voriconazole plasma trough levels (C_min) out of target range are often observed with little knowledge about predisposing influences.

Objectives: To determine the distribution and influencing factors on voriconazole blood levels of patients treated on intensive- or intermediate care units (ICU/IMC).

Patients and methods: Data were collected retrospectively from patients with at least one voriconazole trough plasma level on ICU/IMC (n = 153) to determine the proportion of sub-, supra- or therapeutic plasma levels. Ordinal logistic regression analysis was used to assess factors hindering patients to reach voriconazole target range.

Results: Of 153 patients, only 71 (46%) reached the target range at the first therapeutic drug monitoring, whereas 66 (43%) patients experienced too-low and 16 (10%) too-high plasma levels. Ordinal logistic regression analysis identified the use of extra corporeal membrane oxygenation (ECMO), low international normalized ratio (INR) and aspartate-aminotransferase (AST) serum levels as predictors for too-low plasma levels.

Conclusion: Our data highlight an association of ECMO, INR and AST levels with voriconazole plasma levels, which should be considered in the care of critically ill patients to optimize antifungal therapy with voriconazole.