• Jason A Roberts, Fekade Sime, Jeffrey Lipman, Maria 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, Wai Tat Wong, Markus Zeitlinger, and Claire Roger.
• University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
• Crit Care Resusc. 2023 Mar 1; 25 (1): 151-5.

ObjectiveTo describe whether contemporary dosing of antifungal drugs achieves therapeutic exposures in critically ill patients that are associated with optimal outcomes. Adequate antifungal therapy is a key determinant of survival of critically ill patients with fungal infections. Critical illness can alter an antifungal agents' pharmacokinetics, increasing the risk of inappropriate antifungal exposure that may lead to treatment failure and/or toxicity.Design Setting And ParticipantsThis international, multicentre, observational pharmacokinetic study will comprise adult critically ill patients prescribed antifungal agents including fluconazole, voriconazole, posaconazole, isavuconazole, caspofungin, micafungin, anidulafungin, and amphotericin B for the treatment or prophylaxis of invasive fungal disease. A minimum of 12 patients are targeted for enrolment for each antifungal agent, across 12 countries and 30 intensive care units to perform descriptive pharmacokinetics. Pharmacokinetic sampling will occur during two dosing intervals (occasions): firstly, between days 1 and 3, and secondly, between days 4 and 7 of the antifungal course, collecting three samples per occasion. Patients' demographic and clinical data will be collected.Main Outcome MeasuresThe primary endpoint of the study is attainment of pharmacokinetic/pharmacodynamic target exposures that are associated with optimal efficacy. Thirty-day mortality will also be measured.Results And ConclusionsThis study will describe whether contemporary antifungal drug dosing achieves drug exposures associated with optimal outcomes. Data will also be used for the development of antifungal dosing algorithms for critically ill patients. Optimised drug dosing should be considered a priority for improving clinical outcomes for critically ill patients with fungal infections.© 2023 Published by Elsevier B.V. on behalf of College of Intensive Care Medicine of Australia and New Zealand.

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