Department of Pharmacy Practice, College of Pharmacy, University of Findlay, 1000 N. Main Street, 45840, Findlay, OH, USA.
Department of Pharmacy, Mercy Health - St. Anne Hospital, 43623, Toledo, OH, USA.
BMC Nephrol. 2024 Feb 27;25(1):73. doi: 10.1186/s12882-024-03469-2.
The Tablo Hemodialysis System is a new innovative kidney replacement therapy (KRT) providing a range of options for critically ill patients with acute kidney injury. The use of various effluent rate and treatment durations/frequencies may clear antibiotics differently than traditional KRT. This Monte Carlo Simulation (MCS) study was to develop antibiotic doses likely to attain therapeutic targets for various KRT combinations.
Published body weights and pharmacokinetic parameter estimates were used to predict drug exposure for cefepime, ceftazidime, imipenem, meropenem and piperacillin/tazobactam in virtual critically ill patients receiving five KRT regimens. Standard free β-lactam plasma concentration time above minimum inhibitory concentration targets (40-60%fT and 40-60%fT) were used as efficacy targets. MCS assessed the probability of target attainment (PTA) and likelihood of toxicity for various antibiotic dosing strategies. The smallest doses attaining PTA ≥ 90% during 1-week of therapy were considered optimal.
MCS determined β-lactam doses achieving ∼90% PTA in all KRT options. KRT characteristics influenced antibiotic dosing. Cefepime and piperacillin/tazobactam regimens designed for rigorous efficacy targets were likely to exceed toxicity thresholds.
The flexibility offered by new KRT systems can influence β-lactam antibiotic dosing, but doses can be devised to meet therapeutic targets. Further clinical validations are warranted.
Tablo 血液透析系统是一种新的创新肾脏替代疗法 (KRT)，为急性肾损伤的重症患者提供了一系列选择。不同的流出率和治疗持续时间/频率的使用可能会以不同于传统 KRT 的方式清除抗生素。这项蒙特卡罗模拟 (MCS) 研究旨在为各种 KRT 组合开发可能达到治疗目标的抗生素剂量。
使用已发表的体重和药代动力学参数估算值来预测虚拟重症患者接受五种 KRT 方案时头孢吡肟、头孢他啶、亚胺培南、美罗培南和哌拉西林/他唑巴坦的药物暴露情况。标准游离β-内酰胺血浆浓度时间超过最小抑菌浓度目标（40-60%fT 和 40-60%fT）被用作疗效目标。MCS 评估了各种抗生素剂量策略的目标达标概率 (PTA) 和毒性发生可能性。在 1 周治疗期间达到 PTA≥90%的最小剂量被认为是最佳剂量。
MCS 确定了在所有 KRT 方案中达到约 90%PTA 的β-内酰胺剂量。KRT 特征会影响抗生素的剂量。针对严格疗效目标设计的头孢吡肟和哌拉西林/他唑巴坦方案可能会超过毒性阈值。
新 KRT 系统提供的灵活性可能会影响β-内酰胺抗生素的剂量，但可以设计剂量以达到治疗目标。需要进一步的临床验证。
