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, J. A., Sime, F. B., Lipman, J., Hernández-Mitre, M. P., Baptista, J. P., Brüggemann, R. J., Darvall, J., De Waele, J. J., Dimopoulos, G., Lefrant, J. Y., Mat Nor, M. B., Rello, J., Seoane, L., Slavin, M. A., Valkonen, M., Venditti, M., Ceccarelli, G., Wong, W. T., Zeitlinger, M., & Roger, C. (2025)
The Screening Antifungal Exposure in Intensive Care Units (SAFE-ICU) study, published in Intensive Care Medicine, provides important evidence on the adequacy of antifungal drug exposure in critically ill patients, an area where dosing guidance remains limited.
The study included 339 patients across 30 ICUs in 12 countries and assessed whether contemporary dosing of triazole, echinocandin, and polyene antifungals achieve therapeutic exposures expected to lead to optimal outcomes. Despite standard dosing, more than 25% of patients receiving antifungal treatment did not reach predefined pharmacokinetic/pharmacodynamic (PK/PD) targets, particularly for voriconazole, posaconazole, micafungin, and amphotericin B. These findings highlight substantial variability in drug exposure, largely driven by altered pharmacokinetics in critically ill patients.
The scale and scope of this study, spanning multiple continents and healthcare systems, underscore the need for more individualised dosing strategies and reinforce the role of therapeutic drug monitoring in antifungal stewardship. Future analyses from this dataset will aim to directly inform dosing strategies for these antifungals, helping to ensure critically ill patients receive effective and safe therapy tailored to their unique clinical context.
This publication is a major output from the SAFE-ICU study and reflects the strength of CRE RESPOND’s international research partnerships in addressing critical gaps in infectious diseases pharmacotherapy.
