46-Population Pharmacokinetic Evaluation of Cefepime in Critically Ill Adults
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Pharmacology, 2021
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The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.


Erin Frazee Barreto

Introduction/Hypothesis: Anti-pseudmonal beta-lactams such as cefepime are the cornerstone of antibiotic regimens for intensive care unit (ICU) patients. Significant variability exists in the pharmacokinetics (PK) of cefepime in ICU patients. The objective of this study was to develop an optimized PK model for cefepime in this population using opportunistic sampling from remnant serum samples collected as part of routine care.

Methods: A prospective cohort of adults admitted to the ICU at Mayo Clinic, Rochester, MN from November 2018 to March 2020 treated with cefepime (bolus over 30 minutes) were studied. Patients with acute kidney injury, dialysis dependence or exposed to ECMO were excluded. We performed a PK evaluation based on the total cefepime concentrations obtained from 3 serum samples per patient (residual specimen from blood obtained during ICU care). Samples were stored refrigerated before assaying for approximately 3-days. A 1-compartment non-linear mixed effects model was fit using Monolix. Model inputs included dose, interval, concentration, body surface area (BSA) and estimated creatinine clearance (eCrCl) based on the Cockcroft-Gault equation.

Results: There were 84 ICU patients included with a mean ± SD weight of 84 ± 23 kg, BSA of 1.94 ± 0.28 m^2, and eCrCl of 112 ± 67 mL/min. Final parameter estimates (relative standard errors) in the population included a Vd of 31.7 L (9.0%) with a between subject variability (BSV) of 35% and a clearance of 5.6 L/h (4.5%) with a BSV of 28.5%. Volume of distribution (Vd) varied with BSA, while drug clearance varied with eCrCl. Individual predictions for observed concentrations were appropriate at the patient level, with only 3.7% outliers for the 90% predictive interval.

Conclusions: This study demonstrated the feasibility of using stored specimens to develop a population PK model for adults treated with cefepime in the ICU. The cefepime Vd observed was approximately 2-fold higher than that reported in the literature for non-ICU patients. Understanding the nuances of an individual patient's PK variability in critical illness is a first step toward precision dosing. Additional studies are needed to test optimized cefepime models more broadly for therapeutic individiualization.


Meta Tag
Content Type Presentation
Knowledge Area Pharmacology
Knowledge Level Advanced
Membership Level Select
Tag Antibiotics
Tag Pharmacokinetics Pharmacodynamics
Year 2021
critically ill adults
Mayo Clinic


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