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ation; moderate-quality proof) [10]. Apart from, panel members of scientific societies like European Society of Intensive Care Medicine (ESICM) [11] recommends voriconazole TDM to become routinely performed when it is applied in critically ill patients; indeed, TDM-guided voriconazole dosing enhanced clinical response and decreased voriconazole discontinuation due to adverse events [12]. Ultimately, timely TDM for triazole antifungal agents is viewed as by the Mycoses Study Group Education and Investigation Consortium as a core element for best practices in antifungal stewardship [13]. Within this context, we carried out a retrospective multicenter cohort study in Lyon University Hospital primarily based around the determination of serum voriconazole trough concentrations in adult patients who received voriconazole as a treatment in the course of their ICU stay. The primary objective of this study was to describe factors related to voriconazole trough concentrations around the first TDM occasion. The secondary objectives have been to evaluate the effect of trough voriconazole concentrations on occurrence of adverse effects.Supplies and methods Study designThis study was a 2-year (2018019) retrospective multicenter cohort study applying hospital database. Six intensive care units (ICUs) such as medical (two units), surgical (1 unit), and mixed healthcare and surgical (three units) ICUs, situated in 4 health-related centers were involved. Adult individuals 18 years-old who received voriconazole as a therapy and had no less than a single TDM during ICU remain were included within the study. There was no upper age limit for inclusion. Sufferers who weren’t sampled 12 +/- 2 h after voriconazole administration, patients who received an antifungal combination, pediatric patients, and sufferers who werePLOS A single | doi.org/10.1371/journal.pone.0260656 November 24,two /PLOS ONEAssociation among voriconazole exposure and SOFA score in critically ill patientsnot admitted to an ICU, weren’t incorporated. Serum voriconazole concentrations have been determined in the pharmacology laboratory of Lyon hospital using a validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) process. The reduce limit of quantification was 0.05 mg/L plus the inter-day precision was much less than 5.9 over the calibration variety (0.05.89 mg/L). Voriconazole trough concentration (Cmin) was sampled 12 +/- 2 h following voriconazole administration. Target trough voriconazole serum concentration ranged from 1 to five mg/L [11]. Based on this target and based on results observed on the initially TDM occasion, individuals were categorized into 3 groups: sufferers who had optimal voriconazole concentrations (Cmin = 1 to 5 mg/L), supratherapeutic concentrations (Cmin five mg/L) and subtherapeutic concentrations (Cmin 1 mg/L). During the study period, big diagnostic, therapeutic, and infection handle standards, remained unchanged. The study was registered in Clinicaltrials.gov (BACE1 custom synthesis NCT04502771). This study was part of an antifungal stewardship program implemented in our institution which important aim would be to promote the optimal use of antifungals.Ethics statementThis was a non-interventional study, devoid of any additional process. Information had been collected Caspase 9 list through routine patient care. This study was carried out in accordance with the Declaration of Helsinki and national and institutional requirements. The study was authorized by the institutional Ethics Committee (N01). As a result of retrospective nature of the study, formal consent was not expected. Electronic records had been beneath the a