Are contemporary antifungal doses sufficient for critically ill patients? Outcomes from an international, multicenter pharmacokinetics study for screening antifungal exposure in intensive care units— the SAFE‑ICU study

Roberts, Jason A. and Sime, Fekade B. and Lipman, Jeffrey and Hernandez‑Mitre, Maria Patricia and Baptista, Joao Pedro and Bruggemann, Roger J. and Darvall, Jai and Waele, Jan J. De and Dimopoulos, George and Lefran, Jean‑Yves and Mat Nor, Mohd Basri and Rello, Jordi and Seoane, Leonardo and Slavin, Monica A. and Valkonen, Miia and Venditti, Mario and Ceccarelli, Giancarlo and Wong, Wai Tat and Zeitlinger, Markus and Roger, Claire (2025) Are contemporary antifungal doses sufficient for critically ill patients? Outcomes from an international, multicenter pharmacokinetics study for screening antifungal exposure in intensive care units— the SAFE‑ICU study. Intensive Care Medicine, 51 (2). pp. 302-317. ISSN 0342-4642 E-ISSN 1432-1238

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Abstract

Purpose Appropriate antifungal therapy is a major determinant of survival in critically ill patients with invasive fungal disease. We sought to describe whether contemporary dosing of antifungals achieves therapeutic exposures in critically ill patients. Methods In a prospective, open-label, multicenter pharmacokinetic study, intensive care unit (ICU) patients prescribed azoles, echinocandins, or polyene antifungals for treatment or prophylaxis of invasive fungal disease were enrolled. Blood samples were collected on two occasions, with three samples taken during a single dosing interval on each occasion. Total concentrations were centrally measured using validated chromatographic methods. Pharmacokinetic parameters were estimated using noncompartmental methods. Antifungal dosing adequacy was assessed using predefined PK/PD targets. Results We included 339 patients from 30 ICUs across 12 countries. Median age 62 (interquartile range [IQR], 51–70) years, median APACHE II score 22 (IQR, 17–28), and 61% males. Antifungal therapy was primarily prescribed for treatment (80.8%). Fluconazole was the most frequently prescribed antifungal (40.7%). The most common indication for treatment was intra-abdominal infection (30.7%). Fungi were identified in 45% of patients, of which only 26% had a minimum inhibitory concentration available. Target attainment was higher for patients receiving prophylaxis (> 80% for most drugs). For patients receiving treatment, low target attainment was noted for voriconazole (57.1%), posaconazole (63.2%), micafungin (64.1%) and amphotericin B (41.7%). Conclusion This study highlights the varying degrees of target attainment across antifungal agents in critically ill patients. While a significant proportion of patients achieved the predefined PK/PD targets, wide variability and subtherapeutic exposures persist.

Item Type:	Article (Journal)
Additional Information:	5608/119581
Uncontrolled Keywords:	Antifungals, Pharmacokinetics, Critically ill, Intensive care unit, Invasive fungal disease
Subjects:	R Medicine > RC Internal medicine > RC82 Medical Emergencies, Critical Care, Intensive Care, First Aid
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine Kulliyyah of Medicine > Department of Anaesthesiology & Intensive Care
Depositing User:	Dr. Mohd Basri Mat Nor
Date Deposited:	28 Mar 2025 14:32
Last Modified:	28 Mar 2025 15:15
URI:	http://irep.iium.edu.my/id/eprint/119581

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