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Updated: Oct 8, 2025

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
The Pharmacokinetics of Beta-Lactam Antibiotics Using Scavenged Samples in Pediatric Intensive Care Patients: The
Stef Schouwenburg1, Enno D Wildschut2, M de Hoog2
1Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
Insights
Optimizing antibiotic dosing in pediatric intensive care units (PICUs) is crucial. The EXPAT Kids study investigates if current beta-lactam antibiotic regimens achieve therapeutic targets in critically ill children, exploring novel sampling methods.
Area of Science:
- Pediatric Intensive Care
- Pharmacokinetics and Pharmacodynamics
- Infectious Diseases
Background:
- Optimized antibiotic exposure is vital for pediatric intensive care unit (PICU) patients.
- Traditional dosing strategies are inadequate due to extreme pharmacokinetic variability in PICU populations.
- Scavenged sampling offers a potential method for routine therapeutic drug monitoring (TDM) and biomarker research.
Purpose of the Study:
- To evaluate if current empiric dosing of beta-lactam antibiotics achieves therapeutic targets in PICU patients.
- To analyze the pharmacokinetic and pharmacodynamic profiles of commonly used beta-lactams in critically ill children.
- To assess the feasibility of using scavenged samples for antibiotic exposure quantification.
Main Methods:
- A single-center, exploratory pharmacokinetic and pharmacodynamic study.
- Inclusion of 140 pediatric patients over 24 months.
- Measurement of serum antibiotic concentrations (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, meropenem) at various time points.
- Validation of scavenged heparinized astrup syringes for antibiotic quantification.
Main Results:
- Primary outcome: time above minimum inhibitory concentration (100%ƒT > MIC and 100%ƒT>4xMIC).
- Secondary outcomes include disease severity, safety, length of stay, and inflammatory biomarkers.
- Data will provide insights into beta-lactam PK parameters and target attainment.
Conclusions:
- Findings will inform optimal beta-lactam dosing strategies in PICU patients.
- Scavenged sampling may reduce blood draw workload and enhance data collection.
- The study addresses the need for precise antibiotic dosing in critically ill children.
Abstract:
Background: Emerging evidence supports the importance of optimized antibiotic exposure in pediatric intensive care unit (PICU) patients. Traditional antibiotic dosing is not designed for PICU patients, as the extreme pharmacokinetic (PK) behavior of drugs threatens the achievement of optimal antibiotic treatment outcomes. Scavenged sampling is a sampling strategy which may have positive implications for routine TDM and PK research, as well as monitoring other biomarkers. EXPAT Kids study was designed to analyze whether current empiric dosing regimens of frequently used beta-lactam antibiotics achieve defined therapeutic target concentrations in PICU patients. Methods: A mono-centre, exploratory pharmacokinetic and pharmacodynamic study was designed to assess target attainment of beta-lactam antibiotics. One hundred forty patients will be included within 24 months after start of inclusion. At various time points serum concentration of the study antibiotic (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, and meropenem) are determined. In parallel with these sampling moments, residual material is collected to validate the use of blood of scavenged heparinized astrup syringes for the quantification of antibiotic exposure. The primary outcome is the time that the free (unbound) concentration of the study antibiotic remains above one to four the minimal inhibitory concentration during a dosing interval (100%ƒT > MIC and 100%ƒT>4xMIC). Other included outcomes are disease severity, safety, length of stay, and inflammatory biomarkers. Discussion: Potentially, scavenged sampling may enrich the EXPAT Kids dataset, and reduce additional blood sampling and workload for clinical personnel. The findings from the EXPAT Kids study will lead to new insights in the PK parameters of beta-lactams and consecutive effects on target attainment and clinical outcomes. Is there a need for more precision in dosing? Netherlands Trial Register Number: Trial NL9326.
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