Clinical Pharmacology Department, University Hospital of Nantes, Nantes, France; EA 3826 Thérapeutiques Cliniques et Expérimentales des Infections, University of Nantes, Nantes, France.
Intensive Care Unit, Anaesthesia and Critical Care Department, University Hospital of Nantes, Nantes, France.
Int J Antimicrob Agents. 2018 Jul;52(1):28-34. doi: 10.1016/j.ijantimicag.2018.02.015. Epub 2018 Mar 1.
Morbid obesity is known to increase the risk of surgical site infections. Optimal concentrations of prophylactic antibacterial drugs are required. Using Monte Carlo simulations, the aim of this work was to build a population pharmacokinetics model for a morbidly obese population to assess a 4000-mg dose of cefazolin recommended by the guidelines and to propose new administration schemes. One hundred and seventeen morbidly obese patients (mean body mass index, 46.95 kg/m) received 4000 mg of cefazolin intravenously before sleeve gastrectomy. Using population pharmacokinetics modelling and Monte Carlo simulations, probabilities of target attainment (PTAs) (subcutaneous tissue concentration of cefazolin above the minimum inhibitory concentration (MIC) throughout the surgical procedure was targeted) were determined. For Staphylococcus spp. and Streptococcus spp., which are the most frequent species isolated from post-surgical infections in bariatric surgery (MIC usually ≤2 mg/L), PTA remains greater than 0.9 until 2 h after administration of 4000 mg of cefazolin. For MIC up to 4 mg/L, efficient prophylaxis was checked until 1 h after the initial administration. A 3000-mg regimen followed by a continuous infusion (1000 mg/h) achieves these two targets until 4 h after the loading dose. A 2000-mg and a 3000-mg regimen do not achieve sufficient concentrations. According to the duration of surgery and MIC values, an initial administration of 4000 mg should be sufficient, but for extended surgeries continuous infusion can be considered.
病态肥胖已知会增加手术部位感染的风险。需要使用最佳浓度的预防性抗菌药物。本研究采用蒙特卡罗模拟，旨在构建病态肥胖人群的群体药代动力学模型，以评估指南推荐的头孢唑林 4000mg 剂量，并提出新的给药方案。117 例病态肥胖患者（平均体重指数 46.95kg/m）在接受袖状胃切除术前行 4000mg 头孢唑林静脉注射。采用群体药代动力学模型和蒙特卡罗模拟，确定目标浓度（subcutaneous tissue concentration of cefazolin above the minimum inhibitory concentration (MIC) throughout the surgical procedure was targeted）的达标概率（PTAs）。对于金黄色葡萄球菌和链球菌，它们是肥胖手术中术后感染最常见的分离菌（MIC 通常≤2mg/L），4000mg 头孢唑林给药后 2 小时内 PTA 仍大于 0.9。对于 MIC 达 4mg/L，初始给药后 1 小时内检查有效预防。3000mg 剂量方案加持续输注（1000mg/h）可在负荷剂量后 4 小时内达到这两个目标。2000mg 和 3000mg 剂量方案无法达到足够的浓度。根据手术持续时间和 MIC 值，初始给药 4000mg 可能就足够了，但对于延长的手术，可以考虑持续输注。
