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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
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Ceftazidime-Avibactam Pharmacokinetic Comparative In Vivo/In Vitro Study in a Critically Ill Children Under

Michael Thy1,2,3, Alexandre Debs4, Gabrielle Lui2,5

  • 1Service de Médecine Intensive et Réanimation Infectieuse, Hôpital Bichat Claude-Bernard, AP-HP, Université Paris Cité, Paris, France.

Pharmacology Research & Perspectives
|August 29, 2025
PubMed

Insights

Ceftazidime-avibactam pharmacokinetics in critically ill children on continuous renal replacement therapy (CRRT) require careful monitoring. Higher doses or continuous infusion may be necessary for effective treatment.

Area of Science:

  • Pharmacology
  • Critical Care Medicine
  • Antimicrobial Resistance

Background:

  • Increasing antimicrobial resistance necessitates novel therapeutic strategies.
  • Ceftazidime-avibactam is a key antibiotic combination for treating resistant infections.
  • Critically ill children often require renal replacement therapy, impacting drug pharmacokinetics.

Purpose of the Study:

  • To compare the pharmacokinetics of ceftazidime and avibactam in a simulated pediatric CRRT setting.
  • To evaluate the impact of continuous venovenous hemodiafiltration (CVVHDF) on ceftazidime-avibactam levels.
  • To provide dosing recommendations for ceftazidime-avibactam in pediatric CRRT patients.

Main Methods:

  • In vitro simulation of continuous venovenous hemodiafiltration (CVVHDF).
  • Pharmacokinetic analysis of ceftazidime and avibactam.
  • Comparison with existing in vivo pediatric CRRT data.

Main Results:

  • Simulated CVVHDF significantly altered ceftazidime-avibactam pharmacokinetics.
  • Drug clearance was higher than anticipated in the simulated CRRT model.
  • Existing dosing regimens may lead to sub-therapeutic levels in pediatric CRRT patients.

Conclusions:

  • Therapeutic drug monitoring is crucial for ceftazidime-avibactam in pediatric CRRT.
  • Dosing adjustments, such as higher doses or continuous infusion, are likely needed.
  • Further research is warranted to optimize ceftazidime-avibactam dosing in this population.

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