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本研究的目的是根据患者不同程度的肾功能损伤和细菌耐药情况,探索哌拉西林/他唑巴坦在肾功能不全患者中的给药方案.本研究基于已发表的群体药动学模型,使用非线性混合效应模型(NONMEM)法进行2700次的仿真,最佳的给药方案定义为不达标的患者的概率低于10％.研究发现对于肾功能轻度至中度损害的患者,常规4/0.5 g哌拉西林/他唑巴坦,q12h,30 min给药方案是合适的.但当MIC为8 mg/L或16 mg/L时,需要调整给药方案为q8h或q6h或者延长输注时间为2--6 h.当MIC大于32 mg/L时,12-24 g/天的高剂量哌拉西林持续输注是唯一可以达到目标值的给药方案.对于严重肾损伤的病人,推荐采用低剂量并延长输注4-6 h.本研究中给出不同MIC(直到64 mg/L)下,肾功能不全患者给予哌拉西林/他唑巴坦的具体推荐给药方案,研究结果将会为哌拉西林/他唑巴坦在临床上的精确给药提供帮助.“,”In the present study,we aimed to investigate the optimal dosage regimens of piperacillin/tazobactam in patients with chronic kidney disease according to their different classes of renal function based on bacterial resistance.A total of 2700 simulations were applied based on a published population pharmacokinetic and pharmacodynamic model using nonlinear mixed effects modeling (NONMEM) software.Permissible optimal dosage regimens were defined as those associated with a less than 10％ of patients whose probabilities of target attainment (PTA) were not attain target.For patients with mild to moderate renal injury,4/0.5 g of piperacillin/tazobactam every 12 h in 30 min intermittent infusion could attain the target.If the MIC (minimum inhibitory concentration) for the pathogen was 8 mg/L or 16 mg/L,either an 8-h or 6-h dosing interval or extended 2-6 h infusion regimen had to be used to achieve the outcome of the therapy.Regarding MIC was up to above 32 mg/L,a high do se of piperacillin (12-24 g/d) in continuous infusion was the only approach that could achieve the effective target in patients with renal dysfunction.A low dose with extended 4-6 h infusion regimen was recommended for patients with severe renal injury.Our study identified permissible optimal piperacillin/tazobactam dosage regimens for patients with renal dysfunction with an MIC up to 64 mg/L.The findings of this study would be helpful for precise administration of piperacillin/tazobactam in clinical practice.