Journal Article

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

van Vliet, Peter, Verkaik, Nelianne J., Abdulla, Alan, Rietdijk, Wim J.R., Ewoldt, Tim M.J., Purmer, Ilse M., Osthoff, Michael, Endeman, Henrik, Dräger, Sarah, Koch, Birgit C.P.

2025

Overview

This study aims to assess pharmacodynamic target attainment in critically ill patients and identify factors influencing target attainment and mortality outcomes. We 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. The 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). A 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. •Pharmacodynamic target attainment of beta-lactam antibiotics was high.•Pharmacodynamic target attainment of ciprofloxacin was low.•Higher exposure of beta-lactams was an independent risk factor of 28-day mortality.•The impact of antibiotic target attainment on clinical outcome merits further investigations.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Aged / Anti-Bacterial Agents - therapeutic use / Antibiotics / Antimicrobial agents / beta Lactam Antibiotics / beta-lactams / beta-Lactams - therapeutic use / Ciprofloxacin / Ciprofloxacin - therapeutic use / Creatinine / Critical Illness - mortality / Critically ill / Drug dosages / E coli / Epidemiology / Female / Humans / Male / Middle Aged / Mortality / Organ Dysfunction Scores / Pathogens / Patients / Pharmacodynamic target attainment / Pharmacodynamics / Regression analysis / Sepsis / Software / Therapeutic drug monitoring / Toxicity