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Published on: August 30, 2018
Low Target Attainment of Intravenous Cefuroxime in Critically Ill Term Neonates and Children: A Pooled Population
Stef Schouwenburg1,2, Tim Preijers3,4, Roelie M Wösten-van Asperen5
1Department of Hospital Pharmacy, Erasmus University Medical Centre, Rotterdam, The Netherlands. s.schouwenburg@erasmusmc.nl.
Insights
Current cefuroxime dosing may lead to under-exposure in critically ill children due to augmented renal function. Individualized dosing strategies are needed to optimize cefuroxime (a beta-lactam antibiotic) exposure and efficacy in pediatric intensive care units.
Area of Science:
- Pediatric Pharmacology
- Critical Care Medicine
- Antimicrobial Stewardship
Background:
- Cefuroxime, a beta-lactam antibiotic, is frequently used in pediatric intensive care units.
- Optimizing cefuroxime dosing is crucial for effective treatment in critically ill children.
Purpose of the Study:
- To characterize intravenous cefuroxime pharmacokinetics in critically ill pediatric patients.
- To evaluate target attainment of current cefuroxime dosing regimens.
- To propose improved dosing strategies for cefuroxime.
Main Methods:
- Population pharmacokinetic (popPK) analysis using NONMEM.
- Simulation of different cefuroxime dosage regimens (intermittent and continuous).
- Assessment of target attainment (100% time > 4x MIC) for cefuroxime.
Main Results:
- A two-compartment popPK model described cefuroxime disposition, with postnatal age and creatinine clearance as key covariates.
- Current cefuroxime dosing regimens showed suboptimal target attainment, especially in patients with varying eGFR levels.
- Alternative regimens (e.g., continuous infusion) improved cefuroxime target attainment, particularly in older children and those with augmented renal clearance.
Conclusions:
- Current cefuroxime dosing regimens may result in under-exposure in pediatric patients with augmented renal function.
- Individualized dosing is recommended to optimize cefuroxime exposure and therapeutic efficacy.
- Further research into tailored cefuroxime dosing strategies for pediatric populations is warranted.
Background And Objective:
Cefuroxime is a widely prescribed beta-lactam antibiotic, particularly in pediatric cardiac and medical-surgical intensive care units. The aim of this study was to describe intravenous cefuroxime disposition in critically ill pediatric patients. Moreover, target attainment of currently applied dosing regimens was evaluated, and suggestions for improving these dosing regimens were provided.
Methods:
Two datasets were pooled for population pharmacokinetic (popPK) analysis, using NONMEM version 7.5. To assess the optimal target attainment (> 90% of patients with 100% time [T] > [4×] minimal inhibitory concentration [MIC]8mg/L), pharmacokinetic (PK) profiles of different dosage regimens (intermittent/continuous) were simulated using the estimated popPK parameters.
Results:
The cohort consisted of 45 pediatric patients with a median (interquartile range [IQR]) age of 391 days [31-3505] and body weight of 9.0 kg [5.0-29.8]. A two-compartment popPK model with first-order elimination and allometric scaling best described cefuroxime disposition. Intravenous cefuroxime clearance was estimated at 5.29 L/h/70 kg. Postnatal age and creatinine clearance (mL/min/1.73 m2) were the best descriptive covariates for the maturation of cefuroxime clearance. Simulations evaluating the current cefuroxime dosing regimens stratified for estimated glomerular filtration rate (eGFR) levels illustrated moderate (< 90%) (eGFR < 30 and 30-80 mL/min/1.73 m2) and poor (< 20%) (eGFR 80-120 and > 120 mL/min/1.73 m2) cefuroxime target attainment across the entire age range. Alternative dosing regimens, including four times daily schedules and continuous infusion, improved target attainment, particularly in older children and those with augmented renal clearance.
Conclusions:
These findings indicate that underexposure due to augmented renal function is possible when applying the current cefuroxime dosing regimens. Future research should focus on individualized dosing strategies to optimize cefuroxime exposure and efficacy in pediatric populations.
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