Sarah Dräger, Tim M J Ewoldt, Alan Abdulla, Wim J R Rietdijk, Nelianne J Verkaik, Peter van Vliet, Ilse M Purmer, Michael Osthoff, Birgit C P Koch, Henrik Endeman
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The study outcome included the rate of pharmacodynamic target attainment of 100 % ƒT<sub>>1xEpidemiological cut-off value (ECOFF)</sub> for beta-lactams, and of fAUC<sub>0-24h</sub>/ECOFF>125 for ciprofloxacin at T1.</p><p><strong>Results: </strong>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<sub>>1xECOFF</sub> (28.9 % vs. 12.5 %; p = 0.01). 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引用次数: 0
摘要
研究目的本研究旨在评估重症患者的药效学目标达成情况，并确定影响目标达成和死亡率结果的因素：我们分析了 DOLPHIN 试验的数据。我们对 DOLPHIN 试验的数据进行了分析。在开始治疗后的前 36 小时（T1）内测量了β-内酰胺类药物和环丙沙星的峰值和谷值浓度。研究结果包括β-内酰胺类药物 100 % ƒT>1x 流行病学临界值（ECOFF）和环丙沙星在 T1 的 fAUC0-24h/ECOFF>125 的药效学目标达标率：β-内酰胺类药物的达标率为 78.1%（n = 228/292），环丙沙星的达标率为 41.5%（n = 39/94）。估计肾小球滤过率较低和 SOFA 评分较高与达标率有关。在接受β-内酰胺类药物治疗的患者中，ƒT>1xECOFF达标率为100%的患者的28天死亡率明显更高（28.9% vs. 12.5%；p = 0.01）。在多变量分析中，达到 100 % ƒT>4xECOFF 的患者 28 天死亡率较高（OR 2.70，95 % CI 1.36-5.48 vs. OR 1.28，95 % CI 0.53-3.34），而达到 100 % ƒT>1xECOFF 的患者 28 天死亡率较低（OR 2.70，95 % CI 1.36-5.48 vs. OR 1.28，95 % CI 0.53-3.34）：观察发现，β-内酰胺类药物的达标率较高（100 % ƒT>1xECOFF ），而环丙沙星的达标率较低。达到 100 % ƒT>4xECOFF 的暴露与 28 天死亡率有关。抗生素目标达标率对临床结果的影响需要成为未来研究的重点。
Target attainment of beta-lactam antibiotics and ciprofloxacin in critically ill patients and its association with 28-day mortality.
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 fAUC0-24h/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.
期刊介绍：
The Journal of Critical Care, the official publication of the World Federation of Societies of Intensive and Critical Care Medicine (WFSICCM), is a leading international, peer-reviewed journal providing original research, review articles, tutorials, and invited articles for physicians and allied health professionals involved in treating the critically ill. The Journal aims to improve patient care by furthering understanding of health systems research and its integration into clinical practice.
The Journal will include articles which discuss:
All aspects of health services research in critical care
System based practice in anesthesiology, perioperative and critical care medicine
The interface between anesthesiology, critical care medicine and pain
Integrating intraoperative management in preparation for postoperative critical care management and recovery
Optimizing patient management, i.e., exploring the interface between evidence-based principles or clinical insight into management and care of complex patients
The team approach in the OR and ICU
System-based research
Medical ethics
Technology in medicine
Seminars discussing current, state of the art, and sometimes controversial topics in anesthesiology, critical care medicine, and professional education
Residency Education.
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