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Target-controlled infusion of cefepime in critically Ill patients

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

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MLA
Jonckheere, Stijn, et al. “Target-Controlled Infusion of Cefepime in Critically Ill Patients.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 64, no. 1, 2020.
APA
Jonckheere, S., De Neve, N., Verbeke, J., De Decker, K., Brandt, I., Boel, A., … Colin, P. J. (2020). Target-controlled infusion of cefepime in critically Ill patients. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 64(1).
Chicago author-date
Jonckheere, Stijn, Nikolaas De Neve, Jan Verbeke, Koen De Decker, Inger Brandt, An Boel, Jan Van Bocxlaer, Michel Struys, and Pieter J. Colin. 2020. “Target-Controlled Infusion of Cefepime in Critically Ill Patients.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 64 (1).
Chicago author-date (all authors)
Jonckheere, Stijn, Nikolaas De Neve, Jan Verbeke, Koen De Decker, Inger Brandt, An Boel, Jan Van Bocxlaer, Michel Struys, and Pieter J. Colin. 2020. “Target-Controlled Infusion of Cefepime in Critically Ill Patients.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 64 (1).
Vancouver
1.
Jonckheere S, De Neve N, Verbeke J, De Decker K, Brandt I, Boel A, et al. Target-controlled infusion of cefepime in critically Ill patients. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 2020;64(1).
IEEE
[1]
S. Jonckheere et al., “Target-controlled infusion of cefepime in critically Ill patients,” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 64, no. 1, 2020.
@article{8655494,
  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.},
  articleno    = {e01552-19},
  author       = {Jonckheere, Stijn and De Neve, Nikolaas and Verbeke, Jan and De Decker, Koen and Brandt, Inger and Boel, An and Van Bocxlaer, Jan and Struys, Michel and Colin, Pieter J.},
  issn         = {0066-4804},
  journal      = {ANTIMICROBIAL AGENTS AND CHEMOTHERAPY},
  keywords     = {DEFINING ANTIBIOTIC LEVELS,CARE-UNIT PATIENTS,PREDICTIVE PERFORMANCE,PLASMA-CONCENTRATIONS,VANCOMYCIN,PHARMACODYNAMICS,PIPERACILLIN,OPTIMIZATION,RESISTANCE,CLEARANCE,target-controlled infusion,drug infusion system,cefepime,pharmacokinetics,intensive care unit},
  language     = {eng},
  number       = {1},
  pages        = {9},
  title        = {Target-controlled infusion of cefepime in critically Ill patients},
  url          = {http://dx.doi.org/10.1128/AAC.01552-19},
  volume       = {64},
  year         = {2020},
}

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