β-Lactam dosing in critically ill children: predictors for target non-attainment

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.