title: Healthcare-associated Staphylococcus aureus Bacteremia in Children: Evidence for Reverse Vancomycin Creep and Impact of Vancomycin Trough Values on Outcome.
abstract: BACKGROUND
  Elevated vancomycin minimum inhibitory concentrations (MICs) in Staphylococcus aureus have been associated with worse clinical outcomes in adults. For invasive meticillin-resistant S. aureus (MRSA) infections in adults, the Infectious Diseases Society of America recommends targeting vancomycin serum trough concentrations between 15 and 20 μg/mL. We evaluated trends in vancomycin MICs from healthcare-associated (HCA) S. aureus bacteremia isolates in children in addition to correlating vancomycin serum trough levels with clinical outcomes.
  
  
  METHODS
  Patients and isolates were identified from a prospective S. aureus surveillance study at Texas Children's Hospital (TCH). HCA S. aureus bacteremia isolates from 2003 to 2013 were selected. Vancomycin MICs by E-test were determined and medical records were reviewed. Acute kidney injury (AKI) was defined as doubling of the baseline serum creatinine.
  
  
  RESULTS
  Three hundred forty-one isolates met inclusion criteria. We observed a reverse vancomycin creep among MRSA isolates in the study period with a decline in the proportion of isolates with vancomycin MIC ≥ 2 μg/mL (from 32.7% to 5.6%; P < 0.001). However, the proportion of MSSA isolates with MIC ≥ 2 μg/mL increased (from 2.9% to 9%; P = 0.04). Among patients who had vancomycin troughs performed, there was no difference in duration of bacteremia or fever with vancomycin trough >15 versus <15 μg/mL. A vancomycin trough >15 μg/mL was, however, an independent risk factor for AKI.
  
  
  CONCLUSIONS
  Vancomycin MICs are shifting among HCA S. aureus bacteremia isolates with significant differences between MRSA and MSSA at TCH. Higher vancomycin troughs did not improve outcomes in pediatric HCA S. aureus bacteremia but were associated with increased nephrotoxicity. Further studies are needed to better understand optimal management of children with S. aureus bacteremia.
authors.affiliation: From the *Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas; and †Infectious Diseases Service, Texas Children's Hospital, Houston, Texas.
authors.forename: J Chase
authors.initials: JC
authors.lastname: McNeil
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Kok
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Forbes
authors.forename: Linda
authors.initials: L
authors.lastname: Lamberth
authors.forename: Kristina G
authors.initials: KG
authors.lastname: Hulten
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Vallejo
authors.forename: Edward O
authors.initials: EO
authors.lastname: Mason
authors.forename: Sheldon L
authors.initials: SL
authors.lastname: Kaplan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia; D002675:Child, Preschool; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D013781:Texas / Q000453:epidemiology; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin