Antibiotics (Aug 2024)

Loading Dose of Ceftazidime Needs to Be Increased in Critically Ill Patients: A Retrospective Study to Evaluate Recommended Loading Dose with Pharmacokinetic Modelling

  • Manon Launay,
  • Edouard Ollier,
  • Benjamin Kably,
  • Félicien Le Louedec,
  • Guillaume Thiery,
  • Julien Lanoiselée,
  • Sophie Perinel-Ragey

DOI
https://doi.org/10.3390/antibiotics13080756
Journal volume & issue
Vol. 13, no. 8
p. 756

Abstract

Read online

To rapidly achieve ceftazidime target concentrations, a 2 g loading dose (LD) is recommended before continuous infusion, but its adequacy in critically ill patients, given their unique pharmacokinetics, needs investigation. This study included patients from six ICUs in Saint-Etienne and Paris, France, who received continuous ceftazidime infusion with plasma concentration measurements. Using MONOLIX and R, a pharmacokinetic (PK) model was developed, and the literature on ICU patient PK models was reviewed. Simulations calculated the LD needed to reach a 60 mg/L target concentration and assessed ceftazidime exposure for various regimens. Among 86 patients with 223 samples, ceftazidime PK was best described by a one-compartment model with glomerular filtration rate explaining clearance variability. Typical clearance and volume of distribution were 4.45 L/h and 88 L, respectively. The literature median volume of distribution was 37.2 L. Simulations indicated that an LD higher than 2 g was needed to achieve 60 mg/L in 80% of patients, with a median LD of 4.9 g. Our model showed a 4 g LD followed by 6 g/day infusion reached effective concentrations within 1 h, while a 2 g LD caused an 18 h delay in achieving target steady state.

Keywords