Department of Pharmaceutical and Medical Chemistry-Clinical Pharmacy, Muenster, Germany.
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
Br J Clin Pharmacol. 2019 Dec;85(12):2864-2877. doi: 10.1111/bcp.14121. Epub 2019 Dec 15.
Adequate plasma concentrations of antibiotics during surgery are essential for the prevention of surgical site infections. We examined the pharmacokinetics of 1.5 g cefuroxime administered during induction of anaesthesia with follow-up doses every 2.5 hours until the end of surgery. We built a physiologically based pharmacokinetic model with the aim to ensure adequate antibiotic plasma concentrations in a heterogeneous population.
A physiologically based pharmacokinetic model (PK-Sim /MoBi ) was developed to investigate unbound plasma concentrations of cefuroxime. Blood samples from 25 thoracic surgical patients were analysed with high-performance liquid chromatography. To evaluate optimized dosing regimens, physiologically based pharmacokinetic model simulations were conducted.
Dosing simulations revealed that a standard dosing regimen of 1.5 g every 2.5 hours reached the pharmacokinetic/pharmacodynamic target for Staphylococcus aureus. However, for Escherichia coli, >50% of the study participants did not reach predefined targets. Effectiveness of cefuroxime against E. coli can be improved by administering a 1.5 g bolus immediately followed by a continuous infusion of 3 g cefuroxime over 3 hours.
The use of cefuroxime for perioperative antibiotic prophylaxis to prevent staphylococcal surgical site infections appears to be effective with standard dosing of 1.5 g preoperatively and follow-up doses every 2.5 hours. In contrast, if E. coli is relevant in surgeries, this dosing regimen appears insufficient. With our derived dose recommendations, we provide a solution for this issue.
手术期间抗生素的血浆浓度应足够高，以预防手术部位感染。我们研究了麻醉诱导时给予 1.5g 头孢呋辛，随后每 2.5 小时给予一次维持剂量直至手术结束时的药代动力学。我们构建了一个基于生理的药代动力学模型，旨在确保在异质人群中达到足够的抗生素血浆浓度。
开发了一个基于生理的药代动力学模型（PK-Sim / MoBi）来研究头孢呋辛的游离血浆浓度。对 25 例胸外科患者的血样进行了高效液相色谱分析。为了评估优化的给药方案，进行了基于生理的药代动力学模型模拟。
给药模拟显示，每 2.5 小时给予 1.5g 的标准剂量方案可达到金黄色葡萄球菌的药代动力学/药效学目标。然而，对于大肠杆菌，超过 50%的研究参与者未达到预设目标。通过立即给予 1.5g 头孢呋辛的负荷剂量，然后连续输注 3g 头孢呋辛 3 小时，可以提高头孢呋辛对大肠杆菌的疗效。
在预防金黄色葡萄球菌手术部位感染的围手术期预防性使用头孢呋辛时，术前给予标准剂量 1.5g，随后每 2.5 小时给予一次维持剂量，似乎是有效的。相比之下，如果大肠杆菌在手术中相关，这种给药方案似乎不足够。我们提出的剂量建议提供了解决这个问题的方案。
