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Improving cefazolin exposure in critically ill children using population pharmacokinetic model
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  • Clémence Rivaud,
  • Mehdi Oualha,
  • elodie salvador,
  • Emmanuelle Bille,
  • Delphine Callot,
  • agathe beranger,
  • Léo Froelicher,
  • Steeve Rouillon,
  • Julie Toubiana,
  • Sihem Benaboud,
  • Sylvain Renolleau,
  • Jean-Marc Tréluyer,
  • Déborah Hirt,
  • Noémie De Cacqueray
Clémence Rivaud
Necker-Enfants Malades Hospitals
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Mehdi Oualha
Necker-Enfants Malades Hospitals
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elodie salvador
Necker-Enfants Malades Hospitals
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Emmanuelle Bille
Necker-Enfants Malades Hospitals
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Delphine Callot
Hospital Cochin
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agathe beranger
Necker-Enfants Malades Hospitals
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Léo Froelicher
Hospital Cochin
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Steeve Rouillon
Hospital Cochin
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Julie Toubiana
Necker-Enfants Malades Hospitals
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Sihem Benaboud
Hospital Cochin
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Sylvain Renolleau
Necker-Enfants Malades Hospitals
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Jean-Marc Tréluyer
Hospital Cochin
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Déborah Hirt
Hospital Cochin
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Noémie De Cacqueray
Necker-Enfants Malades Hospitals

Corresponding Author:[email protected]

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Abstract

Aim: Population pharmacokinetics (PK) models may be effective to improve antibiotic exposure with individualized dosing. The aim of the study is to assess cefazolin exposure using a population PK model in critically ill children. Methods: We conducted a single center observational study including children under 18 years old who had cefazolin plasma monitoring before and after the model implementation. First concentration at steady state of each cefazolin course was analyzed. Optimal exposure was defined by concentrations values ranged from free concentration over 4 times the MIC for 100% of the dosing interval to total trough or plateau concentration under 100 mg/L. Results: Fifty-eight patients were included, of whom 39 and 19 children received conventional dosing or model-informed dosing, respectively. Median [range] age was 2.3 [0.1-17] years old and median weight was 14.2 [2.9-72] kg. There were more continuous infusions (CI) in the model group than in the conventional group (n=19/19 (100%) vs n=23/39 (59%)). Compared to conventional dosing, model-informed dosing provided more optimal exposure (n=17/39 (44%) vs n= 15/19 (79%), p=0.01) and less underexposure (n= 18/39 (46%) vs n= 2/19 (10%), p=0.008), without increasing overexposure (n= 4/39 (10%) vs n= 2/19 (11%), p=1). Moreover, the time to reach a 50% decrease of C Reactive Protein levels was significantly shorter in the model group than the conventional group (3 [0.5-13] vs 4 [1-34]; p=0.045. Conclusions: Use of individualized cefazolin model-informed dosing improves critically ill children’s exposure. Further studies are needed to assess the clinical benefit of cefazolin PK model application.
18 Apr 2024Submitted to British Journal of Clinical Pharmacology
25 Apr 2024Submission Checks Completed
25 Apr 2024Assigned to Editor
25 Apr 2024Review(s) Completed, Editorial Evaluation Pending
19 Jul 20241st Revision Received
20 Jul 2024Submission Checks Completed
20 Jul 2024Assigned to Editor
20 Jul 2024Review(s) Completed, Editorial Evaluation Pending
07 Aug 2024Editorial Decision: Accept