• Journal of critical care · Sep 2024

    Target attainment of beta-lactam antibiotics and ciprofloxacin in critically ill patients and its association with 28-day mortality.

    • Sarah Dräger, Tim M J Ewoldt, Alan Abdulla, Wim J R Rietdijk, Nelianne J Verkaik, Peter van Vliet, Ilse M Purmer, Michael Osthoff, KochBirgit C PBCPDepartment of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands; Rotterdam Clinical Pharmacometrics Group, Rotterdam, the Netherlands., Henrik Endeman, and DOLPHIN investigators.
    • Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands; Rotterdam Clinical Pharmacometrics Group, Rotterdam, the Netherlands; Department of Internal Medicine, University Hospital Basel, Basel, Switzerland. Electronic address: s.drager@erasmusmc.nl.
    • J Crit Care. 2024 Sep 13: 154904154904.

    ObjectivesThis study aims to assess pharmacodynamic target attainment in critically ill patients and identify factors influencing target attainment and mortality outcomes.MethodsWe analysed data from the DOLPHIN trial. Beta-lactam and ciprofloxacin peak and trough concentration were measured within the first 36 h (T1) after initiation of treatment. The study outcome included the rate of pharmacodynamic target attainment of 100 % ƒT>1xEpidemiological cut-off value (ECOFF) for beta-lactams, and of fAUC0-24h/ECOFF>125 for ciprofloxacin at T1.ResultsThe target attainment rates were 78.1 % (n = 228/292) for beta-lactams, and 41.5 % (n = 39/94) for ciprofloxacin, respectively. Lower estimated glomerular filtration rate and higher SOFA score were associated with target attainment. In patients receiving beta-lactams, 28-day mortality was significantly higher in patients who attained 100 % ƒT>1xECOFF (28.9 % vs. 12.5 %; p = 0.01). In the multivariate analysis, attainment of 100 % ƒT>4xECOFF, but not 100 % ƒT>1xECOFF, was associated with a higher 28-day mortality (OR 2.70, 95 % CI 1.36-5.48 vs. OR 1.28, 95 % CI 0.53-3.34).ConclusionsA high rate of target attainment (100 % ƒT>1xECOFF) for beta-lactams and a lower rate for ciprofloxacin was observed. Achieving exposures of 100 % ƒT>4xECOFF was associated with 28-day mortality. The impact of antibiotic target attainment on clinical outcome needs to be a focus of future research.Copyright © 2024. Published by Elsevier Inc.

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