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β-Lactam dosing in critically ill children: predictors for target non-attainment
Stef Schouwenburg1,2, Tim Preijers1,2, Roelie M Wösten-Van Asperen3
1Department of Hospital Pharmacy, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Insights
High kidney function (eGFR ≥90) in pediatric ICU patients is linked to inadequate β-lactam antibiotic exposure. Adjusting dosages or using continuous infusions may be necessary for optimal treatment in these children.
Area of Science:
- Pharmacology
- Pediatric Critical Care Medicine
- Infectious Diseases
Background:
- β-Lactam antibiotics are frequently used in pediatric intensive care units (PICUs).
- The therapeutic target for β-lactams is achieving unbound plasma concentrations above 1-4 times the minimum inhibitory concentration (MIC) for 100% of the dosing interval.
- Identifying factors that predict achieving this target is crucial for effective treatment.
Purpose of the Study:
- To assess the attainment of β-lactam antibiotic targets in PICU patients.
- To identify patient characteristics associated with failing to reach therapeutic targets.
Main Methods:
- A prospective observational study was conducted in two Dutch PICUs.
- Paediatric patients receiving cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, or meropenem were enrolled.
- Free drug concentrations were measured against epidemiological cut-off MICs (ƒT>MICECOFF and ƒT>4×MICECOFF).
Main Results:
- Only 27.6% of patients achieved 100% ƒT>MICECOFF, and 13.7% achieved 100% ƒT>4×MICECOFF.
- An estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m² was a significant predictor of target non-attainment.
- No significant association was found between target attainment and ICU length of stay, though age correlated with length of stay.
Conclusions:
- Elevated kidney function (eGFR ≥90) is associated with sub-therapeutic β-lactam levels in PICU patients.
- Consideration of kidney function is vital for dose adjustments to optimize antibiotic exposure.
- Findings suggest higher doses or continuous infusions may be needed for specific pediatric patient groups to ensure adequate β-lactam exposure.
Introduction:
β-Lactam antibiotics are among the most frequently prescribed antibiotics on the paediatric ICU (PICU). For β-lactam antibiotics, unbound plasma concentrations above at least one to four times the MIC for 100% of the dosing interval (100% ƒT > 1-4×MIC) have been proposed as the pharmacodynamic target. This study aimed to determine target attainment of β-lactam antibiotics in PICUs and to identify predictors of target non-attainment.
Patients And Methods:
This prospective observational study was performed in two PICUs in the Netherlands. We enrolled paediatric patients treated with the following β-lactam antibiotics: cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin and meropenem. The free concentration above the bacterial epidemiological cut-off minimum inhibitory concentration (ƒT > MICECOFF and ƒT > 4×MICECOFF) was determined. Secondary endpoints were estimated regression models for examining the association of target non-attainment with patient characteristics and clinical outcomes.
Results:
A total of 116 patients were included, of whom 27.6% achieved 100% ƒT > MICECOFF and 13.7% achieved 100% ƒT > 4×MICECOFF. Regression analysis identified an estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 as a risk factor for target non-attainment. In addition, no significant association between the 100% ƒT > MICECOFF target attainment and ICU length of stay (LOS) was found. However, for both pharmacodynamic targets, a significant correlation was found between LOS and age in years.
Conclusions:
This study found an eGFR ≥90 mL/min/1.73 m2 to be associated with target non-attainment, indicating that kidney function should be taken into account when identifying individuals who may require higher dosages. These results may help identify subpopulations of paediatric patients requiring higher dosages or continuous infusion in order to achieve adequate β-lactam exposure.
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