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Updated: Jun 5, 2025
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Population pharmacokinetics and dose optimization of ceftazidime in critically ill children
Mengting Li1, Liuliu Gao1, Zuo Wang2
1Department of Clinical Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Insights
This study developed a population pharmacokinetic model for ceftazidime in critically ill children. Optimized dosing regimens ensure effective treatment for most infections, but higher doses may be needed for resistant bacteria.
Area of Science:
- Pharmacology
- Pediatric Intensive Care
- Clinical Pharmacy
Background:
- Ceftazidime is a crucial antibiotic for treating serious infections in critically ill children.
- Optimizing ceftazidime dosing in pediatric intensive care unit (PICU) patients is essential due to altered pharmacokinetics in critical illness.
- Accurate dosing ensures therapeutic efficacy while minimizing toxicity.
Purpose of the Study:
- To develop a population pharmacokinetic (PPK) model for ceftazidime in critically ill children.
- To optimize ceftazidime dosing regimens for this vulnerable patient population.
- To establish evidence-based dosing recommendations considering patient weight and renal function.
Main Methods:
- A prospective pharmacokinetic study was conducted in 88 critically ill children (0.03-15 years).
- A one-compartment linear model was developed using Non-linear Mixed Effects (NLME) modeling.
- Monte Carlo simulations were used to determine optimal dosing for achieving 70% time above minimum inhibitory concentration (MIC).
Main Results:
- Weight and estimated glomerular filtration rate (eGFR) were significant covariates for ceftazidime clearance.
- The developed PPK model accurately described ceftazidime pharmacokinetics in critically ill children.
- Recommended regimens achieved >90% probability of target attainment (PTA) for MICs up to 8 mg/L.
Conclusions:
- A robust population pharmacokinetic model for ceftazidime in critically ill children was established.
- Individualized dosing recommendations based on weight and eGFR are proposed.
- Current standard doses are effective for susceptible pathogens (MIC ≤ 8 mg/L), but higher doses may be necessary for ceftazidime-resistant infections (MIC = 16 mg/L).
Objective:
The aim of this study was to develop a population pharmacokinetic model for ceftazidime in critically ill children in the pediatric intensive care unit (PICU) and optimize an appropriate dosing regimen for this population.
Methods:
We performed a prospective pharmacokinetic study on critically ill children aged 0.03-15 years. A population pharmacokinetic model was developed using the NLME program. Statistical and graphical methods were used to assess the stability and predictive performance of the model. Monte Carlo simulations were conducted to determine the optimal ceftazidime dosing regimen to achieve 70% fT > minimum inhibitory concentration (MIC).
Results:
This study included 88 critically ill children and 100 ceftazidime serum concentrations. The pharmacokinetic characteristics of ceftazidime were best described by a one-compartment linear elimination model. The weight and estimated glomerular filtration rate (eGFR) were determinant covariates for the clearance (CL) of ceftazidime. The recommended ceftazidime dosage regimens achieved a probability of target attainment (PTA) >90% for critically ill children at MIC values of 2, 4, and 8 mg/L. For bacterial infection at an MIC of 16 mg/L, it is difficult to achieve effective pharmacodynamic (PD) targets in vivo with the commonly used dose of ceftazidime.
Conclusion:
The population pharmacokinetic model of ceftazidime was established in critically ill children. Based on this model, we recommend evidence-based, individualized dosing regimens for subgroups with different weights and renal functions. The current daily dosage for children adequately meets the treatment requirements for MICs of 2, 4, and 8 mg/L, while for bacterial infection at an MIC of 16 mg/L, an elevated dosage regimen may be required.
Clinical Trial Registration:
https://www.medicalresearch.org.cn/login, Identifier MR-42-22-000220.
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