Tilanus Alwin M, Shields Ryan K, Lodise Thomas P, Drusano George L
Vida Medical/Department of Infectious Diseases, Bogotá, Colombia.
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Clin Infect Dis. 2025 Jul 18;80(6):1275-1280. doi: 10.1093/cid/ciaf038.
Based on the fact that beta-lactam antibiotics demonstrate time-dependent killing, different dosing strategies have been implemented to increase the time that free (unbound) antibiotic concentrations remain above the minimal inhibitory concentration, including prolonged and continuous infusion. Multiple studies have been performed that compared continuous with traditional intermittent infusion to improve outcomes in patients with severe sepsis. These studies have yielded inconsistent results for patients, as measured by clinical response to treatment and mortality due to heterogeneity of included patients, pathogens, dosing strategies, and the absence of therapeutic drug monitoring. The Continuous Infusion versus Intermittent Administration of Meropenem in Critically Ill Patients and Beta-Lactam Infusion Group trials failed to show a difference in mortality between patients randomized to receive continuous or intermittent infusion of beta-lactam antibiotics deeper understanding of the pharmacokinetic and pharmacodynamic mechanisms that occur in critically ill patients should guide us in dose optimization and improvement in methodology for future clinical trials.
基于β-内酰胺类抗生素呈现时间依赖性杀菌这一事实，已实施了不同的给药策略以延长游离（未结合）抗生素浓度维持在最低抑菌浓度之上的时间，包括延长输注和持续输注。已经开展了多项研究，比较持续输注与传统间歇输注对严重脓毒症患者预后的影响。这些研究针对患者得出了不一致的结果，这是由纳入患者的异质性、病原体、给药策略以及缺乏治疗药物监测等因素导致的，具体衡量指标为对治疗的临床反应和死亡率。“美罗培南在重症患者中的持续输注与间歇给药”试验以及“β-内酰胺输注组”试验均未显示，随机接受β-内酰胺类抗生素持续或间歇输注的患者在死亡率上存在差异。对重症患者体内发生的药代动力学和药效学机制有更深入的了解，应能指导我们进行剂量优化，并改进未来临床试验的方法。
