Infectious Diseases - Internal Medicine Departments, Bellvitge University Hospital, University of Barcelona, L'Hopspitalet de Llobregat, Spain.
Pharmacy Department, Division of Medicines, Hospital Clinic de Barcelona, Barcelona, Spain.
Eur J Clin Pharmacol. 2021 Aug;77(8):1169-1180. doi: 10.1007/s00228-021-03100-5. Epub 2021 Feb 9.
Ceftriaxone total and unbound pharmacokinetics (PK) can be altered in critically ill patients with septic shock and hypoalbuminemia receiving continuous veno-venous hemodiafiltration (CVVHDF). The objective of this study was to determine the dosing strategy of ceftriaxone that maximizes the probability of maintaining the concentration above the MIC of the susceptible bacteria (≤2 mg/L by the EUCAST) for a 100% of the dosing interval (100% ƒT).
In a prospective PK study in the intensive care units of two tertiary Spanish hospitals, six timed blood samples were collected per patient; for each sample, ceftriaxone total and unbound concentrations were measured using a liquid chromatography coupled to tandem mass spectrometry method. Population PK analysis and Monte-Carlo simulations were performed using NONMEMv.7.3®.
We enrolled 8 critically ill patients that met the inclusion criteria (47 blood samples). Median age (range) was 70 years (47-85), weight 72.5 kg (40-95), albumin concentration 24.2 g/L (22-34), APACHE II score at admission 26 (17-36), and SOFA score on the day of study 12 (9-15). The unbound fraction (ƒ) of ceftriaxone was 44%, and total CL was 1.27 L/h, 25-30% higher than the CL reported in septic critically ill patients not receiving renal replacement therapies, and dependent on albumin concentration and weight. Despite this increment in ƒ and CL, Monte-Carlo simulations showed that a dose of 1 g once-daily ceftriaxone is sufficient to achieve a 100% ƒT for MICs ≤2 mg/L for any range of weight and albumin concentration.
Once-daily 1 g ceftriaxone provides optimal exposure in critically ill patients with septic shock and hypoalbuminemia receiving CVVHDF.
在接受连续性静脉-静脉血液透析滤过（CVVHDF）治疗的伴有脓毒性休克和低白蛋白血症的重症患者中，头孢曲松的总浓度和游离浓度的药代动力学（PK）可能会发生改变。本研究的目的是确定头孢曲松的给药方案，该方案可使 100%的给药间隔（100% ƒT）内药物浓度维持在敏感菌（EUCAST 标准为≤2mg/L）的 MIC 以上，概率最大化。
在西班牙两家三级医院的重症监护病房进行的一项前瞻性 PK 研究中，每位患者采集 6 个时间点的血样；对于每个样本，使用液相色谱-串联质谱法测量头孢曲松的总浓度和游离浓度。使用 NONMEMv.7.3®进行群体 PK 分析和 Monte-Carlo 模拟。
我们共纳入 8 名符合纳入标准的重症患者（共 47 个血样）。中位年龄（范围）为 70 岁（47-85 岁），体重 72.5kg（40-95kg），白蛋白浓度 24.2g/L（22-34g/L），入院时的急性生理学与慢性健康状况评分系统 II （APACHE II）评分为 26 分（17-36 分），研究当天的序贯器官衰竭评估（SOFA）评分 12 分（9-15 分）。头孢曲松的游离分数（ƒ）为 44%，总清除率（CL）为 1.27L/h，比未接受肾脏替代治疗的脓毒症重症患者的 CL 高 25-30%，且与白蛋白浓度和体重相关。尽管 ƒ和 CL 增加，但 Monte-Carlo 模拟显示，对于任何体重和白蛋白浓度范围，每日一次给予 1g 头孢曲松即可达到 MIC≤2mg/L 时的 100% ƒT。
在接受 CVVHDF 治疗的伴有脓毒性休克和低白蛋白血症的重症患者中，每日一次给予 1g 头孢曲松可提供最佳的暴露度。
