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

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.