Target-Controlled Infusion of Cefepime in Critically Ill Patients: single center experience

Stijn Jonckheere*, Nikolaas De Neve, Jan Verbeke, Koen De Decker, Inger Brandt, An Boel, Jan Van Bocxlaer, Michel M. R. F. Struys, Pieter J. Colin

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

75 Downloads (Pure)

Abstract

Attainment of appropriate pharmacokinetic-pharmacodynamic (PK-PD) targets for antimicrobial treatment is challenging in critically ill patients, particularly for cefepime, which exhibits a relative narrow therapeutic-toxic window compared to other beta-lactam antibiotics. Target-controlled infusion (TCI) systems, which deliver drugs to achieve specific target drug concentrations, have successfully been implemented for improved dosing of sedatives and analgesics in anesthesia. We conducted a clinical trial in an intensive care unit (ICU) to investigate the performance of TCI for adequate target attainment of cefepime. Twenty-one patients treated with cefepime according to the standard of care were included. Cefepime was administered through continuous infusion using TCI for a median duration of 4.5 days. TCI was based on a previously developed population PK model incorporating the estimated creatinine clearance based on the Cockcroft-Gault formula as the input variable to calculate cefepime clearance. A cefepime blood concentration of 16 mg/liter was targeted. To evaluate the measured versus predicted plasma concentrations, blood samples were taken (median of 10 samples per patient), and total cefepime concentrations were measured using ultraperformance liquid chromatography-tandem mass spectrometry. The performance of the TCI system was evaluated using Varvel criteria. Half (50.3%) of the measured cefepime concentrations were within +/- 30% around the target value of 16 mg liter(-1). The wobble was 11.4%, the median performance error (MdPE) was 21.1%, the median absolute performance error (MdAPE) was 32.0%, and the divergence was -3.72% h(-1). Based on these results, we conclude that TCI is useful for dose optimization of cefepime in ICU patients.

Original languageEnglish
Article numberARTN e01552-19
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume64
Issue number1
Early online date4-Nov-2019
DOIs
Publication statusPublished - Jan-2020

Keywords

  • target-controlled infusion
  • drug infusion system
  • cefepime
  • pharmacokinetics
  • intensive care unit
  • DEFINING ANTIBIOTIC LEVELS
  • CARE-UNIT PATIENTS
  • PREDICTIVE PERFORMANCE
  • PLASMA-CONCENTRATIONS
  • VANCOMYCIN
  • PHARMACODYNAMICS
  • PIPERACILLIN
  • OPTIMIZATION
  • RESISTANCE
  • CLEARANCE

Cite this