Urinary Biomarkers and Attainment of Cefepime Therapeutic Targets in Critically Ill Children

Abstract

INTRODUCTION: The recommended therapeutic target for cefepime (FEP) is the time above MIC (fT>MIC). The frequency of target attainment and risk factor for sub-therapeutic concentrations in children have not been extensively studied. METHODS: We performed a prospective observational pilot study in children in our PICU receiving standard dosing of FEP for suspected sepsis (≥2 SIRS criteria). Three FEP concentrations were measured per subject and a urine sample was collected prior to PK sampling for measurement of urinary biomarkers. We used log linear regression to calculate the fT>MIC for each subject across a range of MIC values (1-16 µg/mL). We compared clinical factors/biomarkers between patients who did and did not achieve 100% fT>MIC for 8 µg/mL (cut-point for Pseudomonas) and tested the correlation between covariates and FEP troughs. RESULTS: 21 subjects were enrolled (median SIRS criteria: 3). PK sampling occurred after a median of 5 doses (range: 3-9). 43% of subjects achieved 100% fT>MIC for an MIC of 8 µg/mL. Younger age (p=.005), higher estimated GFR (p=.03), and lower urinary NGAL (p=.006) and KIM-1 (.03) were associated with failure to attain 100% fT>8 µg/mL. Age (r = 0.53), eGFR (r = -0.58), urinary NGAL (r = 0.42) and KIM-1 (r = 0.50) were significantly correlated with FEP troughs. CONCLUSIONS: A significant proportion of critically ill children failed to attain target concentrations for treatment of Pseudomonas aeruginosa with FEP. Younger patients and those with good kidney function (high GFR, low urinary biomarkers) may be at highest risk for subtherapeutic FEP concentrations.