Selig Daniel J, Akers Kevin S, Chung Kevin K, Kress Adrian T, Livezey Jeffrey R, Por Elaine D, Pruskowski Kaitlin A, DeLuca Jesse P
Walter Reed Army Institute of Research, Experimental Therapeutics, Silver Spring, MD 20910, USA.
United States Army Institute of Surgical Research, San Antonio, TX 78234, USA.
Antibiotics (Basel). 2022 May 4;11(5):618. doi: 10.3390/antibiotics11050618.
Critical illness caused by burn and sepsis is associated with pathophysiologic changes that may result in the alteration of pharmacokinetics (PK) of antibiotics. However, it is unclear if one mechanism of critical illness alters PK more significantly than another. We developed a population PK model for piperacillin and tazobactam (pip-tazo) using data from 19 critically ill patients (14 non-burn trauma and 5 burn) treated in the Military Health System. A two-compartment model best described pip-tazo data. There were no significant differences found in the volume of distribution or clearance of pip-tazo in burn and non-burn patients. Although exploratory in nature, our data suggest that after accounting for creatinine clearance (CrCl), doses would not need to be increased for burn patients compared to trauma patients on consideration of PK alone. However, there is a high reported incidence of augmented renal clearance (ARC) in burn patients and pharmacodynamic (PD) considerations may lead clinicians to choose higher doses. For critically ill patients with normal kidney function, continuous infusions of 13.5-18 g pip-tazo per day are preferable. If ARC is suspected or the most stringent PD targets are desired, then continuous infusions of 31.5 g pip-tazo or higher may be required. This approach may be reasonable provided that therapeutic drug monitoring is enacted to ensure pip-tazo levels are not supra-therapeutic.
烧伤和脓毒症所致的危重病与病理生理变化相关，这些变化可能导致抗生素的药代动力学（PK）改变。然而，尚不清楚危重病的一种机制是否比另一种机制更显著地改变药代动力学。我们利用军事卫生系统中治疗的19例危重病患者（14例非烧伤创伤患者和5例烧伤患者）的数据，建立了哌拉西林和他唑巴坦（哌拉西林-他唑巴坦）的群体药代动力学模型。二室模型能最好地描述哌拉西林-他唑巴坦的数据。在烧伤患者和非烧伤患者中，未发现哌拉西林-他唑巴坦的分布容积或清除率有显著差异。尽管本质上是探索性的，但我们的数据表明，在考虑肌酐清除率（CrCl）后，仅从药代动力学角度考虑，与创伤患者相比，烧伤患者无需增加剂量。然而，据报道烧伤患者中高肾清除率（ARC）的发生率较高，药效学（PD）方面的考虑可能会导致临床医生选择更高的剂量。对于肾功能正常的危重病患者，每天持续输注13.5 - 18 g哌拉西林-他唑巴坦更为合适。如果怀疑有高肾清除率或需要最严格的药效学目标，那么可能需要持续输注31.5 g或更高剂量的哌拉西林-他唑巴坦。如果实施治疗药物监测以确保哌拉西林-他唑巴坦水平不超过治疗范围，这种方法可能是合理的。
