title: Risk Factors for Non-Therapeutic Initial Steady-State Vancomycin Trough Concentrations in Children and Adolescents Receiving High Empiric Doses of Intravenous Vancomycin.
abstract: BACKGROUND
  Achieving vancomycin troughs of 15-20 μg/mL remains challenging in children. Our objective was to identify risk factors associated with non-therapeutic initial vancomycin troughs in children.
  
  
  METHODS
  We conducted a retrospective cohort study of children who received intravenous vancomycin with at least one initial steady-state trough obtained. Patients who achieved therapeutic troughs (15-20 μg/mL in the 20-mg/kg/dose sub-cohort and 10-15 μg/mL in the 15-mg/kg/dose sub-cohort) were compared with those with subtherapeutic troughs (<15 and <10 μg/mL, respectively) and supratherapeutic troughs (>20 and >15 μg/mL, respectively) separately to determine risk factors associated with non-therapeutic troughs.
  
  
  RESULTS
  A total of 153 vancomycin courses in 140 patients met study eligibility criteria. Of 45 patients who received 20 mg/kg/dose of empiric vancomycin, 60, 16, and 24% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2increase in initial creatinine clearance (CrCl) was associated with a 47% increase in the odds of an initial subtherapeutic trough (adjusted odds ratio [aOR] 1.47; 95% CI 0.98-2.22). Of 108 patients who received 15 mg/kg/dose of empiric vancomycin, 62, 19, and 19% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2increase in initial CrCl was associated with an 18% increase in the odds of an initial subtherapeutic trough (aOR 1.18; 95% CI 1.02-1.37).
  
  
  CONCLUSIONS
  Achieving vancomycin troughs of 15-20 μg/mL for severe Gram-positive infections continues to be challenging in children, even at higher empiric doses of 20 mg/kg/dose IV every 6-8 h. Children with higher initial CrCls are particularly susceptible to subtherapeutic initial steady-state vancomycin troughs.
authors.affiliation: Department of Pharmacy, Intermountain Medical Center, Murray, UT, USA.
authors.forename: Whitney R
authors.initials: WR
authors.lastname: Buckel
authors.affiliation: Division of Pediatric Pharmacy, Department of Pharmacy, The Johns Hopkins Hospital, 600 N. Wolfe Street, Carnegie 180, Baltimore, MD, 21287, USA.
authors.forename: Shahira
authors.initials: S
authors.lastname: Ghobrial
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Pranita D
authors.initials: PD
authors.lastname: Tamma
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Milstone
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Division of Pediatric Pharmacy, Department of Pharmacy, The Johns Hopkins Hospital, 600 N. Wolfe Street, Carnegie 180, Baltimore, MD, 21287, USA. ajenh1@jhmi.edu.
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Hsu
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin