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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Therapeutic drug monitoring of piperacillin-tazobactam using spent dialysate effluent in patients receiving continuous venovenous hemodialysis.
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Therapeutic drug monitoring of piperacillin-tazobactam using spent dialysate effluent in patients receiving continuous venovenous hemodialysis.

机译：在接受连续静脉血液透析的患者中，使用用过的透析液流出物监测哌拉西林-他唑巴坦的治疗药物。

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Sepsis and multisystem organ failure are common diagnoses affecting nearly three-quarters of a million Americans annually. Infection is the leading cause of death in acute kidney injury, and the majority of critically ill patients who receive continuous dialysis also receive antibiotics. Dialysis equipment and prescriptions have gradually changed over time, raising concern that current drug dosing recommendations in the literature may result in underdosing of antibiotics. Our research group directed its attention toward antibiotic dosing strategies in patients with acute renal failure (ARF), and we sought data confirming that patients receiving continuous dialysis and antibiotics actually were achieving therapeutic plasma drug levels during treatment. In the course of those investigations, we explored "fast-track" strategies to estimate plasma drug concentrations. As most antimicrobial antibiotics are small molecules and should pass freely through modern high-flux hemodialyzer filters, we hypothesized that continuous renal replacement therapy (CRRT) effluent could be used as the medium for drug concentration measurement by reverse-phase high-pressure liquid chromatography (HPLC). Here we present the first data demonstrating this approach for piperacillin-tazobactam. Paired blood and dialysate trough-peak-trough samples were drawn from 19 patients receiving piperacillin-tazobactam and continuous venovenous hemodialysis (CVVHD). Total, free, and dialysate drug concentrations were measured by HPLC. Dialysate drug levels predicted plasma free drug levels well (r(2) = 0.91 and 0.92 for piperacillin and tazobactam, respectively) in all patients. These data suggest a strategy for therapeutic drug monitoring that minimizes blood loss from phlebotomy and simplifies analytic procedures.
机译：败血症和多系统器官衰竭是常见的诊断，每年影响到近一百万美国人的四分之三。感染是急性肾损伤的主要死亡原因，大多数接受持续透析的危重患者也接受抗生素治疗。透析设备和处方随着时间的推移逐渐变化，引起了人们的关注，即文献中当前的药物剂量建议可能会导致抗生素剂量不足。我们的研究小组将注意力转向了急性肾衰竭（ARF）患者的抗生素用药策略，我们寻求的数据证实接受连续透析和抗生素治疗的患者实际上在治疗过程中达到了血浆药物水平。在这些调查过程中，我们探索了“快速”策略来估计血浆药物浓度。由于大多数抗菌抗生素都是小分子，应自由通过现代高通量血液透析滤池，因此我们假设连续肾脏替代疗法（CRRT）流出物可用作通过反相高压液相色谱法测量药物浓度的介质（ HPLC）。在这里，我们提供了第一个数据，证明了哌拉西林-他唑巴坦的这种方法。从19名接受哌拉西林-他唑巴坦和连续静脉血液透析（CVVHD）的患者中抽取成对的血液和透析液谷-峰-谷样品。通过HPLC测量总的，游离的和透析液的药物浓度。在所有患者中，透析液药物水平均能很好地预测血浆游离药物水平（哌拉西林和他唑巴坦的r（2）= 0.91和0.92）。这些数据提出了一种治疗药物监测的策略，该策略可最大程度地减少静脉放血造成的失血量并简化分析程序。

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