Merino-Bohórquez Vicente, Docobo-Pérez Fernando, Valiente-Méndez Adoración, Delgado-Valverde Mercedes, Cameán Manuel, Hope William W, Pascual Álvaro, Rodríguez-Baño Jesús
Unidad de Gestión de Farmacia Hospitalaria, Hospital Universitario Virgen Macarena, 41009 Sevilla, Spain.
Departamento de Farmacología, Universidad de Sevilla, 41009 Sevilla, Spain.
Antibiotics (Basel). 2021 Mar 25;10(4):348. doi: 10.3390/antibiotics10040348.
This study analyzes the pharmacokinetic variability of piperacillin in non-critically ill patients with Enterobacteriaceae bloodstream infections (EBSI) and explores predicted clinical outcomes and piperacillin-related neurotoxicity under different renal conditions. Hospitalized, non-critically ill patients treated with piperacillin-tazobactam for EBSI were included. Four serum samples per patient were collected and analyzed. A population pharmacokinetic model was developed using the Pmetrics package for R. Monte Carlo simulations of various dosage regimens of 4 g piperacillin, administered q8 h or q12 h by short (0.5 h) or long (4 h) infusion, following the different glomerular filtration rate (GFR) categories used to classify chronic kidney disease (Kidney Disease: Improving Global Outcomes, KDIGO) to determine the probability of target attainment (PTA) using a free drug concentrations above the minimal inhibitory concentration (T > MIC) of 50% for efficacy and targets for piperacillin-associated neurotoxicity. Twenty-seven patients (102 samples) were included. Extended piperacillin infusions reached a PTA > 90% (50%T > MIC) within the susceptibility range, although a loading dose did not greatly improve the expected outcome. Long infusions reduced the expected toxicity in patients with severe renal impairment. The study supports the use of extended infusions of piperacillin in non-critically ill patients with EBSI. No benefits of a loading dose were expected in our population. Finally, extended infusions may reduce the risk of toxicity in patients with severe renal impairment.
本研究分析了哌拉西林在非重症肠杆菌科血流感染（EBSI）患者中的药代动力学变异性，并探讨了不同肾脏状况下预测的临床结局及与哌拉西林相关的神经毒性。纳入了因EBSI接受哌拉西林-他唑巴坦治疗的住院非重症患者。每位患者采集并分析4份血清样本。使用R语言的Pmetrics软件包建立群体药代动力学模型。根据用于对慢性肾脏病进行分类的不同肾小球滤过率（GFR）类别（肾脏病：改善全球预后，KDIGO），对4g哌拉西林以q8h或q12h的给药方案通过短时间（0.5小时）或长时间（4小时）输注进行蒙特卡洛模拟，以确定达到目标概率（PTA），即游离药物浓度高于最低抑菌浓度（T>MIC）50%时的疗效以及哌拉西林相关神经毒性的目标。共纳入27例患者（102份样本）。在药敏范围内，延长哌拉西林输注时间可使PTA>90%（50%T>MIC），尽管负荷剂量并不能显著改善预期结局。长时间输注可降低重度肾功能损害患者的预期毒性。本研究支持在非重症EBSI患者中使用延长输注时间的哌拉西林。在我们的研究人群中，未预期到负荷剂量的益处。最后，延长输注时间可能会降低重度肾功能损害患者的毒性风险。
