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. 2022 May 4;11(5):618.
doi: 10.3390/antibiotics11050618.

Comparison of Piperacillin and Tazobactam Pharmacokinetics in Critically Ill Patients with Trauma or with Burn

Daniel J Selig  1 , Kevin S Akers  2 , Kevin K Chung  3 , Adrian T Kress  1 , Jeffrey R Livezey  3 , Elaine D Por  1 , Kaitlin A Pruskowski  2   3 , Jesse P DeLuca  1
Affiliations

Comparison of Piperacillin and Tazobactam Pharmacokinetics in Critically Ill Patients with Trauma or with Burn

Daniel J Selig et al. Antibiotics (Basel). .

Abstract

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.

Keywords: burns; critical illness; pharmacokinetics; piperacillin; tazobactam.

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Conflict of interest statement

The authors have no conflicts of interest to report. Material has been reviewed by the Walter Reed Army Institute of Research, the Uniformed Services University of the Health Sciences and the United States Institute of Surgical Research. There is no objection to its presentation and/or publication. The views expressed in this article are those of the authors and do not reflect the official policy or position of the USA Army Medical Department, Department of the Army, DoD or the USA Government.

Figures

Figure 1
Figure 1
Goodness of fit plots for final models: (a) piperacillin; (b) tazobactam.
Figure 2
Figure 2
Probability of target attainment for (a) piperacillin intermittent infusions; (b) continuous infusions. Intermittent infusions assumed to be infused over 30 min. Creatinine clearance was randomly selected between 100 and 130 mL/min, with 1000 virtual patients simulated per dosing group.
Figure 3
Figure 3
Time-concentration plots with LOESS trend lines: (a) piperacillin; (b) tazobactam (right).
See this image and copyright information in PMC

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