Bindellini Davide, Simon Philipp, Busse David, Michelet Robin, Petroff David, Aulin Linda B S, Dorn Christoph, Zeitlinger Markus, Huisinga Wilhelm, Wrigge Hermann, Kloft Charlotte
Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany; Graduate Research Training Programme, PharMetrX, Berlin, Germany.
Department of Anaesthesiology and Operative Intensive Care, Faculty of Medicine, University of Augsburg, Augsburg, Germany; Integrated Research and Treatment Center (IFB), Adiposity Diseases, University of Leipzig, Leipzig, Germany; Department of Anesthesiology and Intensive Care Medicine, University of Leipzig Medical Center, Leipzig, Germany.
Br J Anaesth. 2025 Apr;134(4):1041-1049. doi: 10.1016/j.bja.2024.11.044. Epub 2025 Feb 1.
Cefazolin is used as a prophylactic antibiotic to reduce surgical site infections (SSIs). Obesity has been identified as a risk factor for SSIs. Cefazolin dosing recommendations and guidelines are currently inconsistent for obese patients. As plasma and target-site exposure might differ, pharmacokinetic data from the sites of SSIs are essential to evaluate treatment efficacy: these data can be obtained via tissue microdialysis. This analysis was designed to evaluate the need for dosing adaptations in obese patients for surgical prophylaxis.
Data from 15 obese (BMI = 52.6 kg m) and 15 age- and sex-matched nonobese patients (BMI = 26.0 kg m) who received 2 g cefazolin i.v. infusion for infection prophylaxis were included in the analysis. Pharmacokinetic data from plasma and interstitial space fluid (ISF) of adipose tissue were obtained and analysed simultaneously using nonlinear mixed-effects modelling. Dosing regimens were evaluated by calculating the probability of target attainment (PTA) and the cumulative fraction of response (CFR) for plasma and ISF using unbound cefazolin concentration above minimum inhibitory concentration 100% of the time as target (fT = 100%). Dosing regimens were considered adequate when PTA and CFR were ≥90%.
Evaluation of cefazolin doses of 1 and 2 g with redosing at either 3 or 4 h by PTA and CFR in plasma and ISF found 2 g cefazolin with redosing at 4 h to be the most suitable dosing regimen for both obese and nonobese patients (PTA >90% and CFR >90% for both).
This model-based analysis, using fT = 100% as a target, showed that cefazolin dosing adaptations are not required for surgical prophylaxis in obese patients.
头孢唑林用作预防性抗生素以减少手术部位感染（SSIs）。肥胖已被确定为手术部位感染的一个风险因素。目前，针对肥胖患者的头孢唑林给药建议和指南并不一致。由于血浆和靶部位暴露可能不同，来自手术部位感染部位的药代动力学数据对于评估治疗效果至关重要：这些数据可通过组织微透析获得。本分析旨在评估肥胖患者手术预防中调整给药剂量的必要性。
分析纳入了15名肥胖患者（BMI = 52.6 kg/m）和15名年龄及性别匹配的非肥胖患者（BMI = 26.0 kg/m），他们接受了2 g静脉输注头孢唑林以预防感染。使用非线性混合效应模型同时获取并分析血浆和脂肪组织间质液（ISF）的药代动力学数据。通过计算血浆和ISF达到目标的概率（PTA）和反应累积分数（CFR）来评估给药方案，以无结合头孢唑林浓度在最低抑菌浓度之上的时间占比100%为目标（fT = 100%）。当PTA和CFR≥90%时，给药方案被认为是合适的。
通过血浆和ISF中的PTA和CFR评估1 g和2 g头孢唑林在3或4小时重新给药的剂量，发现2 g头孢唑林在4小时重新给药是肥胖和非肥胖患者最合适的给药方案（两者的PTA>90%且CFR>90%）。
以fT = 100%为目标的基于模型的分析表明，肥胖患者手术预防不需要调整头孢唑林的给药剂量。
