title: Evaluation of clinical outcome in children and adolescents receiving vancomycin for invasive infections due to methicillin-resistant Staphylococcus aureus: impact of increasing vancomycin MICs.
abstract: BACKGROUND
  Vancomycin is the preferred drug for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in children. In adults, treatment failure with vancomycin has been associated with an area under the curve/24 hrs /MIC (AUC24/MIC) ratio of ≤400 and high minimum inhibitory concentrations (MIC ≥1.0 mg/L). Vancomycin dosing information to ensure optimal AUC24/MIC in the pediatric population remains limited.
  
  
  METHODS
  A retrospective chart review from August 2008 to 2011 and a prospective study from September 2011 to October 2013 was conducted on all pediatric patients at two hospitals in Brooklyn, NY with positive cultures for MRSA who received vancomycin. Treatment failure was defined as persistent positive cultures (≥5 days) or persistence of clinical symptoms. Vancomycin AUC24/MICs were calculated.
  
  
  RESULTS
  Twenty-three children with MRSA infection, 0-18 years of age, were identified; 18 of 23 (78.3%) were community acquired. MICs of 91% of the isolates were ≥1.5 µg/mL and 9 had MICs of 2 µg/mL. Treatment failure was seen in 12 (52%) patients with MICs of 1.5 µg/mL and above. Vancomycin trough levels >15 µg/mL and AUC24/MIC >400 were achieved in only 18% and 0% of patients, respectively.
  
  
  CONCLUSIONS
  High treatment failure rates with vancomycin was associated with MIC ≥1.5 µg/mL. Current recommended vancomycin dosing in children did not achieve a trough concentration of >15 µg/mL in majority of the patients and none achieved an AUC24/MIC>400.
authors.affiliation: Department of Pediatrics, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Arun
authors.affiliation: Department of Pharmacy Practice, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Swamy
authors.affiliation: Department of Clinical Laboratories, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Jacob
authors.affiliation: Department of Pharmacy Practice, SUNY Downstate Medical Center, Brooklyn, NY, USA.|Touro College of Pharmacy, New York, NY, USA.
authors.forename: Roopali
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Pediatrics, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Kohlhoff
authors.affiliation: Department of Pediatrics, SUNY Downstate Medical Center, Brooklyn, NY, USA - mhammerschlag@downstate.edu.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Hammerschlag
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D009519:New York City; D011446:Prospective Studies; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D017211:Treatment Failure; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin