Pharmacokinetic Analysis of Intravenous Push Cefepime in Burn Patients with Augmented Renal Clearance

Author:

Hill David M1ORCID,Yang Bing2ORCID,Laizure S Casey2ORCID,Boucher Bradley2ORCID,Swanson Joseph M2ORCID,Wood G Christopher2ORCID,Hickerson William L3ORCID,Liu Xiangxia4,Velamuri Sai R4

Affiliation:

1. Department of Pharmacy, Regional One Health , 877 Jefferson Avenue, Memphis, TN 38103 , USA

2. Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center , 881 Madison Avenue, Memphis, TN 38163 , USA

3. Access Pro Medical , 842 River Park Dr., Memphis, TN 38103 , USA

4. Department of Surgery, College of Medicine, University of Tennessee Health Science Center , 910 Madison Ave, Memphis, TN 38163 , USA

Abstract

Abstract Patients with augmented renal clearance (ARC) are a subset of critically ill patients including burn patients that exhibit increased renal elimination of medications beyond that of similarly injured patients. Currently approved maximum regimens of medications primarily eliminated by the kidney, such as cefepime (>90% unchanged in the urine), may be inadequate (eg, compromising the bactericidal activity of cefepime) in patients with ARC. Due to recent resource limitations, centers have changed infusion practices of commonly prescribed medications to intravenous push (IVP), potentially exacerbating the problem of maintaining bactericidal cefepime concentrations. The hypothesis of the study was patients with ARC are not currently achieving adequate target attainment, when receiving cefepime 2 g every 8 h IVP. Eight blood samples were collected from each patient, and concentrations measured via LC–MS/MS. WinNonlin (version 8.3) was used to estimate the pharmacokinetic parameters of cefepime and simulate plasma concentrations of cefepime in each of the ten subjects. Simulations of cefepime plasma concentrations produced by a 2 g dose given every 8 h and a 1 g dose given every 4 h were performed and the time above a MIC of 4 mg/L, 8 mg/L, and 16 mg/L compared. The 2 g every 8 h regimen remained above the breakpoints for 92%, 85%, and 71% of the dosing interval, respectively. The 1 g every 4 h regimen remained above the same breakpoints at a frequency of 100%, 99%, and 92% of the dosing interval. Giving cefepime 1 g every 4 h is a simple approach to increase the likelihood of maintaining the optimal bactericidal activity of cefepime in patients with ARC.

Publisher

Oxford University Press (OUP)

Subject

Rehabilitation,Emergency Medicine,Surgery

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