title: Impact of a hospitalwide increase in empiric pediatric vancomycin dosing on initial trough concentrations.
abstract: OBJECTIVE
  To evaluate the impact of a hospitalwide increase in the recommended vancomycin starting dose from 45 to 60 mg/kg/day on initial vancomycin trough concentrations in children suspected of having an invasive methicillin-resistant Staphylococcus aureus (MRSA) infection.
  
  
  METHODS
  Retrospective medical record review.
  
  
  METHODS
  Dedicated children's hospital located in a tertiary care, academic medical center.
  
  
  METHODS
  A total of 182 children aged 1 month-12 years with normal renal function who had suspected MRSA infections treated with vancomycin during two different starting dose recommendation periods: 45 mg/kg/day divided every 8 hours during July 2006-June 2007 (low-dose group [88 children]) and 60 mg/kg/day divided every 6 hours during July 2008-June 2009 (high-dose group [94 children]).
  
  
  RESULTS
  Data on patient demographics, vancomycin doses, and initial vancomycin trough concentrations were collected. No significant demographic differences were noted between patients in the low-dose and high-dose groups. The mean ± SD initial vancomycin trough level increased from 7 ± 5 μg/ml in the low-dose group to 9 ± 5 μg/ml in the high-dose group (p<0.001). The percentage of patients with an initial trough level less than 5 μg/ml declined from 38% (33/88 children) in the low-dose group to 17% (16/94 children) in the high-dose group (p<0.001), whereas the percentage of patients with an initial trough concentration in the potentially adverse range (> 20 μg/ml) did not change between the two groups (2% vs 2%, p=0.9). Less than 14% (13/94 children) achieved a trough level in the range of 15-20 μg/ml in the high-dose group.
  
  
  CONCLUSIONS
  An increase in the recommended vancomycin starting dose to 60 mg/kg/day decreased the likelihood of an initial low vancomycin trough level (< 5 μg/ml), with no increase in the proportion of patients with trough levels in a potentially toxic range. The 60-mg/kg/day dose did not consistently achieve a vancomycin trough of 15-20 μg/ml, a goal suggested by some experts for adults. Comparative effectiveness studies are needed to directly evaluate vancomycin dosing regimens and clinical outcomes for children with invasive MRSA infections.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of California-San Francisco, San Francisco, California 94143-0503, USA. adam.frymoyer@ucsf.edu
authors.forename: Adam
authors.initials: A
authors.lastname: Frymoyer
authors.forename: B Joseph
authors.initials: BJ
authors.lastname: Guglielmo
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wilson
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Scarpace
authors.forename: Leslie Z
authors.initials: LZ
authors.lastname: Benet
authors.forename: Adam L
authors.initials: AL
authors.lastname: Hersh
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy*; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin