INSERM, U1059, Dysfonction Vasculaire et Hémostase, Saint-Etienne, France
Département d'Anesthésie-Réanimation, CHU de Saint-Etienne, Saint-Etienne, France.
Antimicrob Agents Chemother. 2020 Nov 17;64(12). doi: 10.1128/AAC.01687-20.
Cefuroxime (CXM) is an antibiotic recommended for surgical site infection prevention in cardiac surgery. However, the dosing regimens commonly used do not sustain therapeutic concentrations throughout surgery. The aim of this study was to conduct a population analysis of CXM pharmacokinetics (PK), and to propose an optimized dosing regimen. Adult patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) received a 1,500 mg CXM intravenous bolus followed by a 750 mg bolus at CPB priming, then every 2 h thereafter. Model-based PK simulations were used to develop an optimized dosing regimen and evaluate its efficacy in attaining various concentration thresholds, including those recommended in US and European guidelines. In total, 447 CXM measurements were acquired in 50 patients. A two-compartment model best fit the data, with total body weight and creatinine clearance determining interpatient variability in the central and peripheral volumes of distribution, and in elimination clearance, respectively. Using our optimized dosing regimen, different dosing schemes adapted to body weight and renal function were calculated to attain total concentration thresholds ranging from 12 to 96 mg/liter. Our simulations showed that the dosing regimens recommended in US and European guidelines failed to maintain concentrations above 48 mg/liter. Our individualized dosing strategy was capable of ensuring therapeutic CXM concentrations conforming to each target threshold. Our model yielded an optimized CXM dosing regimen adapted to body weight and renal function, and sustaining therapeutic concentrations consistent with each desired threshold. The optimal target concentration and necessary duration of its maintenance in cardiac surgery still remain unclear.
头孢呋辛（CXM）是一种推荐用于心脏手术部位感染预防的抗生素。然而，常用的给药方案在手术过程中无法维持治疗浓度。本研究的目的是对 CXM 的药代动力学（PK）进行群体分析，并提出优化的给药方案。接受体外循环（CPB）下心脏手术的成年患者接受 1500mg CXM 静脉推注，然后在 CPB 预充时给予 750mg 推注，之后每 2 小时给予一次。基于模型的 PK 模拟用于开发优化的给药方案，并评估其在达到各种浓度阈值（包括美国和欧洲指南推荐的阈值）方面的疗效。在 50 名患者中总共获得了 447 次 CXM 测量值。两室模型最适合数据，总体重和肌酐清除率分别确定了分布中心和外周容积以及消除清除率的个体间变异性。使用我们的优化给药方案，根据体重和肾功能计算了不同的给药方案，以达到总浓度阈值范围从 12 到 96mg/liter。我们的模拟表明，美国和欧洲指南推荐的给药方案未能维持浓度高于 48mg/liter。我们的个体化给药策略能够确保符合每个目标阈值的治疗性 CXM 浓度。我们的模型产生了一种适应体重和肾功能的优化 CXM 给药方案，并维持与每个所需阈值一致的治疗浓度。心脏手术中最佳目标浓度及其维持所需的时间仍不清楚。
