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
Jason A. Roberts, Fekade B. Sime, Jeffrey Lipman, María Patricia Hernández-Mitre, João Pedro Baptista, Roger J. Brüggemann, Jai Darvall, Jan J. De Waele, George Dimopoulos, Jean-Yves Lefrant, Mohd Basri Mat Nor, Jordi Rello, Leonardo Seoane, Monica A. Slavin, Miia Valkonen, Mario Venditti, Giancarlo Ceccarelli, Wai Tat Wong, Markus Zeitlinger, Claire Roger
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引用次数: 0
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.
期刊介绍：
Intensive Care Medicine is the premier publication platform fostering the communication and exchange of cutting-edge research and ideas within the field of intensive care medicine on a comprehensive scale. Catering to professionals involved in intensive medical care, including intensivists, medical specialists, nurses, and other healthcare professionals, ICM stands as the official journal of The European Society of Intensive Care Medicine. ICM is dedicated to advancing the understanding and practice of intensive care medicine among professionals in Europe and beyond. The journal provides a robust platform for disseminating current research findings and innovative ideas in intensive care medicine. Content published in Intensive Care Medicine encompasses a wide range, including review articles, original research papers, letters, reviews, debates, and more.
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