Abstract：
Augmented renal clearance (ARC) is commonly described in critically ill patients, making drug pharmacokinetics even harder to predict in this population. This case report displays the value of therapeutic drug monitoring (TDM) of piperacillin/tazobactam (PTZ) in this population. We identified two patients with ARC and intermittent administration of PTZ who took part in a prospective, descriptive study conducted at Hôpital du Sacré-Cœur de Montréal. Both had plasma samples drawn at peak, middle, and end of their dosing intervals of PTZ. Minimal inhibitory concentrations (MICs) of 4 and 8 mg/L were chosen to evaluate therapeutic target attainment at middle and end of dosing interval. The first patient was a 52-year-old male with a renal clearance rate estimated at 147 mL/min who received 3.375 g PTZ every 6 h. The second patient, a 49-year-old male, had an estimated renal clearance rate of 163 mL/min and received the same regimen. Both patients had piperacillin concentrations above the target MICs at middle of the dosing interval, but they failed to reach a trough concentration above 8 mg/L. The present case report showcases two patients with subtherapeutic PTZ concentrations despite strict following of local administration protocols. This suboptimal administration could not only lead to treatment failure, but also to the selection and growth of resistant pathogens. Implementing TDM would offer the possibility to adjust drug regimens in real-time and prevent situations like these from occurring.
摘要：
背景：在危重患者中通常描述增加的肾脏清除率（ARC），使得在这个人群中药物的药代动力学更加难以预测。该病例报告显示了该人群中哌拉西林/他唑巴坦（PTZ）治疗药物监测（TDM）的价值。
方法：本报告中介绍的患者参与了一项前瞻性研究，在蒙特利尔医院进行的描述性研究。我们确定了两名患有ARC和间歇性PTZ的患者的病例。两者都有在峰值处抽取的血浆样本，PTZ给药间隔的中间和结束。选择4和8mg/L的最小抑制浓度(MIC)来评价在给药间隔的中间和结束时的治疗目标的达成。
结果：第一位患者是一名52岁男性，肾脏清除率估计为147mL/min，每6小时接受3.375gPTZ。第二个病人,一个49岁的男性,估计肾脏清除率为163mL/min，并接受相同的治疗方案。在给药间隔的中间，两个患者的哌拉西林浓度均高于目标MIC，但是它们未能达到8mg/L以上的谷浓度。
结论：次优给药不仅会导致治疗失败，而是抗性病原体的选择和生长。实施TDM将提供实时调整药物方案并防止此类情况发生的可能性。
方法：本报告中介绍的患者参与了一项前瞻性研究，在蒙特利尔医院进行的描述性研究。我们确定了两名患有ARC和间歇性PTZ的患者的病例。两者都有在峰值处抽取的血浆样本，PTZ给药间隔的中间和结束。选择4和8mg/L的最小抑制浓度(MIC)来评价在给药间隔的中间和结束时的治疗目标的达成。
结果：第一位患者是一名52岁男性，肾脏清除率估计为147mL/min，每6小时接受3.375gPTZ。第二个病人,一个49岁的男性,估计肾脏清除率为163mL/min，并接受相同的治疗方案。在给药间隔的中间，两个患者的哌拉西林浓度均高于目标MIC，但是它们未能达到8mg/L以上的谷浓度。
结论：次优给药不仅会导致治疗失败，而是抗性病原体的选择和生长。实施TDM将提供实时调整药物方案并防止此类情况发生的可能性。
