Shotwell Matthew S, Nesbitt Ross, Madonia Phillip N, Gould Edward R, Connor Michael J, Salem Charbel, Aduroja Olufemi A, Amde Milen, Groszek Joseph J, Wei Peilin, Taylor Maria E, Tolwani Ashita J, Fissell William H
Departments of Biostatistics.
Nephrology and Hypertension, and.
Clin J Am Soc Nephrol. 2016 Aug 8;11(8):1377-1383. doi: 10.2215/CJN.10260915. Epub 2016 May 19.
Infection is the most common cause of death in severe AKI, but many patients receiving continuous RRT do not reach target antibiotic concentrations in plasma. Extended infusion of β-lactams is associated with improved target attainment in critically ill patients; thus, we hypothesized that extended infusion piperacillin-tazobactam would improve piperacillin target attainment compared with short infusion in patients receiving continuous RRT.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted an institutional review board-approved observational cohort study of piperacillin-tazobactam pharmacokinetics and pharmacodynamics in critically ill patients receiving continuous venovenous hemodialysis and hemodiafiltration at three tertiary care hospitals between 2007 and 2015. Antibiotic concentrations in blood and/or dialysate samples were measured by liquid chromatography, and one- and two-compartment pharmacokinetic models were fitted to the data using nonlinear mixed effects regression. Target attainment for piperacillin was defined as achieving four times the minimum inhibitory concentration of 16 μg/ml for >50% of the dosing cycle. The probabilities of target attainment for a range of doses, frequencies, and infusion durations were estimated using a Monte Carlo simulation method. Target attainment was also examined as a function of patient weight and continuous RRT effluent rate.
Sixty-eight participants had data for analysis. Regardless of infusion duration, 6 g/d piperacillin was associated with ≤45% target attainment, whereas 12 g/d was associated with ≥95% target attainment. For 8 and 9 g/d, target attainment ranged between 68% and 85%. The probability of target attainment was lower at higher effluent rates and patient weights. For all doses, frequencies, patient weights, and continuous RRT effluent rates, extended infusion was associated with higher probability of target attainment compared with short infusion.
Extended infusions of piperacillin-tazobactam are associated with greater probability of target attainment in patients receiving continuous RRT.
感染是重症急性肾损伤（AKI）最常见的死亡原因，但许多接受连续性肾脏替代治疗（RRT）的患者血浆中抗生素浓度未达到目标值。β-内酰胺类药物延长输注时间与危重症患者目标浓度达标率提高相关；因此，我们推测，与接受连续性RRT的患者短时间输注哌拉西林-他唑巴坦相比，延长输注时间会提高哌拉西林的目标浓度达标率。
设计、地点、参与者及测量方法：我们进行了一项经机构审查委员会批准的观察性队列研究，研究2007年至2015年期间在三家三级医疗机构接受连续性静脉-静脉血液透析和血液透析滤过的危重症患者中哌拉西林-他唑巴坦的药代动力学和药效学。通过液相色谱法测量血液和/或透析液样本中的抗生素浓度，并使用非线性混合效应回归将一室和二室药代动力学模型拟合到数据中。哌拉西林的目标浓度达标定义为在>50%的给药周期内达到最低抑菌浓度16μg/ml的四倍。使用蒙特卡罗模拟方法估计一系列剂量、频率和输注持续时间的目标浓度达标概率。还将目标浓度达标作为患者体重和连续性RRT废液流速的函数进行了研究。
68名参与者有数据可供分析。无论输注持续时间如何，哌拉西林6g/d的目标浓度达标率≤45%，而12g/d的目标浓度达标率≥95%。对于8g/d和9g/d，目标浓度达标率在68%至85%之间。废液流速和患者体重越高，目标浓度达标概率越低。对于所有剂量、频率、患者体重和连续性RRT废液流速，与短时间输注相比，延长输注时间的目标浓度达标概率更高。
接受连续性RRT的患者延长输注哌拉西林-他唑巴坦与更高的目标浓度达标概率相关。
