PDF(Pubmed)
Abstract：
Piperacillin/tazobactam (TZP) is administered intravenously in a fixed ratio (8:1) with the potential for inadequate tazobactam exposure to ensure piperacillin activity against Enterobacterales. Adult patients receiving continuous infusion (CI) of TZP and therapeutic drug monitoring (TDM) of both agents were evaluated. Demographic variables and other pertinent laboratory data were collected retrospectively. A population pharmacokinetic approach was used to select the best kidney function model predictive of TZP clearance (CL). The probability of target attainment (PTA), cumulative fraction of response (CFR) and the ratio between piperacillin and tazobactam were computed to identify optimal dosage regimens by continuous infusion across kidney function. This study included 257 critically ill patients (79.3% male) with intra-abdominal, bloodstream, and hospital-acquired pneumonia infections in 89.5% as the primary indication. The median (min-max range) age, body weight, and estimated glomerular filtration rate (eGFR) were 66 (23-93) years, 75 (39-310) kg, and 79.2 (6.4-234) mL/min, respectively. Doses of up to 22.5 g/day were used to optimize TZP based on TDM. The 2021 chronic kidney disease epidemiology equation in mL/min best modeled TZP CL. The ratio of piperacillin:tazobactam increased from 6:1 to 10:1 between an eGFR of <20 mL/min and >120 mL/min. At conventional doses, the PTA is below 90% when eGFR is ≥100 mL/min. Daily doses of 18 g/day and 22.5 g/day by CI are expected to achieve a >80% CFR when eGFR is 100-120 mL/min and >120-160 mL/min, respectively. Inadequate piperacillin and tazobactam exposure is likely in patients with eGFR ≥ 100 mL/min. Dose regimen adjustments informed by TDM should be evaluated in this specific population.
摘要：
哌拉西林/他唑巴坦（TZP）以固定比例（8：1）静脉内给药，有可能使他唑巴坦暴露不足，以确保哌拉西林对肠杆菌的活性。评估接受TZP连续输注（CI）和两种药物治疗药物监测（TDM）的成年患者。回顾性收集人口统计学变量和其他相关实验室数据。使用群体药代动力学方法来选择预测TZP清除(CL)的最佳肾功能模型。达到目标的概率(PTA)，通过计算累积应答分数(CFR)和哌拉西林和他唑巴坦之间的比率,通过跨肾功能连续输注确定最佳给药方案.这项研究包括257例重症患者（79.3％为男性），血流,以医院获得性肺炎感染占89.5%为主要指征。年龄中位数（最小-最大范围），体重,估计肾小球滤过率(eGFR)为66(23-93)年，75(39-310)kg,和79.2（6.4-234）mL/min，分别。使用高达22.5g/天的剂量来基于TDM优化TZP。以mL/min为单位的2021年慢性肾脏病流行病学方程最佳建模TZPCL。哌拉西林:他唑巴坦的比例在eGFR<20mL/min和>120mL/min之间从6:1增加到10:1。在常规剂量下，当eGFR≥100mL/min时，PTA低于90%。当eGFR为100-120mL/min和>120-160mL/min时，每日剂量为18g/天和22.5g/天的CI有望达到>80％的CFR，分别。eGFR≥100mL/min的患者可能存在哌拉西林和他唑巴坦暴露不足。应在该特定人群中评估由TDM告知的剂量方案调整。
