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

Abstract

Objectives: This study aims to assess pharmacodynamic target attainment in critically ill patients and identify factors influencing target attainment and mortality outcomes.

Methods: 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 fAUC_0-24h/ECOFF>125 for ciprofloxacin at T1.

Results: 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).

Conclusions: 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.

Keywords: Antibiotics; Ciprofloxacin; Critically ill; Pharmacodynamic target attainment; Therapeutic drug monitoring; beta-lactams.