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Antibiotics
Volume 13
Issue 8
10.3390/antibiotics13080756
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Article

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

by
Manon Launay
1,2,*,
Edouard Ollier
3,4,
Benjamin Kably
5,
Félicien Le Louedec
6,
Guillaume Thiery
1,7,
Julien Lanoiselée
8 and
Sophie Perinel-Ragey
1,3
1
Medical Intensive Care Unit, University Hospital of Saint-Etienne, 42000 Saint Etienne, France
2
Pharmacovigilance Department, University Hospital of Saint-Etienne, 42000 Saint Etienne, France
3
Mines Saint-Étienne, Université Jean Monnet, INSERM, U1059, SAINBIOSE, 42000 Saint Etienne, France
4
Clinical Pharmacology Unit, University Hospital of Saint-Etienne, 42000 Saint Etienne, France
5
Pharmacology Unit DMU BioPhyGen, European Hospital Georges-Pompidou, APHP, 75015 Paris, France
6
Cancer Research Center of Toulouse (CRCT), Team 14, INSERM UMR1037, University of Toulouse, CS 53717, 31037 Toulouse, France
7
Research on Healthcare Performance RESHAPE, INSERM U1290, Université Claude Bernard Lyon, 69008 Villeurbanne, France
8
Service d’Anesthésie et de Réanimation Chirurgicale, CHU de Saint-Etienne, 42000 Saint Etienne, France
*
Author to whom correspondence should be addressed.
Antibiotics 2024, 13(8), 756; https://doi.org/10.3390/antibiotics13080756
Submission received: 1 July 2024 / Revised: 24 July 2024 / Accepted: 2 August 2024 / Published: 11 August 2024
(This article belongs to the Special Issue Pharmacokinetic and Antibiotic Dosing for Intensive Care Unit Patients)
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Abstract

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: ceftazidime; loading dose; critically ill patients; pharmacokinetics; volume of distribution; model-based simulations ceftazidime; loading dose; critically ill patients; pharmacokinetics; volume of distribution; model-based simulations

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MDPI and ACS Style

Launay, M.; Ollier, E.; Kably, B.; Le Louedec, F.; Thiery, G.; Lanoiselée, J.; Perinel-Ragey, S. Loading Dose of Ceftazidime Needs to Be Increased in Critically Ill Patients: A Retrospective Study to Evaluate Recommended Loading Dose with Pharmacokinetic Modelling. Antibiotics 2024, 13, 756. https://doi.org/10.3390/antibiotics13080756

AMA Style

Launay M, Ollier E, Kably B, Le Louedec F, Thiery G, Lanoiselée J, Perinel-Ragey S. Loading Dose of Ceftazidime Needs to Be Increased in Critically Ill Patients: A Retrospective Study to Evaluate Recommended Loading Dose with Pharmacokinetic Modelling. Antibiotics. 2024; 13(8):756. https://doi.org/10.3390/antibiotics13080756

Chicago/Turabian Style

Launay, Manon, Edouard Ollier, Benjamin Kably, Félicien Le Louedec, Guillaume Thiery, Julien Lanoiselée, and Sophie Perinel-Ragey. 2024. "Loading Dose of Ceftazidime Needs to Be Increased in Critically Ill Patients: A Retrospective Study to Evaluate Recommended Loading Dose with Pharmacokinetic Modelling" Antibiotics 13, no. 8: 756. https://doi.org/10.3390/antibiotics13080756

APA Style

Launay, M., Ollier, E., Kably, B., Le Louedec, F., Thiery, G., Lanoiselée, J., & Perinel-Ragey, S. (2024). Loading Dose of Ceftazidime Needs to Be Increased in Critically Ill Patients: A Retrospective Study to Evaluate Recommended Loading Dose with Pharmacokinetic Modelling. Antibiotics, 13(8), 756. https://doi.org/10.3390/antibiotics13080756

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