ABSTRACT
OBJECTIVES: To identify associations between augmented renal clearance (ARC) in pediatric patients treated for suspected sepsis and vancomycin pharmacokinetics. ARC has been associated with lower serum drug levels in both adult and pediatric cohorts for multiple drugs. We hypothesize that presence of ARC is associated with subtherapeutic initial vancomycin trough level (VTL). DESIGN: Retrospective study, with patients divided into two groups based on the presence of ARC (estimated glomerular filtration rate [eGFR] above 130 mL/min/1.73 m2) in comparison with VTL. Multivariable logistic regression analysis was performed to evaluate the association between eGFR and subtherapeutic VTL. SETTING: Tertiary children's hospital. PATIENTS: Hospitalized children (0-18 yr) initiated on empiric vancomycin therapy for suspected sepsis. INTERVENTIONS: Retrospective measurement of VTL, eGFR, and clinical variables. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients were treated with empiric vancomycin for sepsis. ARC was present in 32 patients (44%). Subtherapeutic first VTL was present in 40 patients (55%). Higher eGFR was independently associated with subtherapeutic VTL in the multivariable logistic regression analysis. CONCLUSIONS: Subtherapeutic VTL is associated with ARC in our single-center retrospective cohort of children with suspected sepsis. This problem may present a potential risk of treatment failure in Gram-positive sepsis or longer time to clinical response. Prospective studies to investigate the clinical significance and effect of optimizing vancomycin dose in patients with ARC are recommended.
