title: Inadequate vancomycin therapy in term and preterm neonates: a retrospective analysis of trough serum concentrations in relation to minimal inhibitory concentrations.
abstract: BACKGROUND
  Vancomycin is effective against gram-positive bacteria and the first-line antibiotic for treatment of proven coagulase-negative staphylococcal infections. The aim of this study is bipartite: first, to assess the percentage of therapeutic initial trough serum concentrations and second, to evaluate the adequacy of the therapeutic range in interrelationship with the observed MIC-values in neonates.
  
  
  METHODS
  In this study, preterm and term neonates admitted at a tertiary NICU in the Netherlands from January 2009 to December 2012 and treated with vancomycin for a proven gram-positive infection were included. Trough serum concentrations were measured prior to administration of the 5th dose. Trough concentrations in the range of 10 to 15 mg/L were considered therapeutic. Staphylococcal species minimal inhibitory concentrations (MIC's) were determined using the E-test method. Species identification was performed by matrix-assisted laser desorption/ionisation mass spectrometry.
  
  
  RESULTS
  Of the 112 neonates, 53 neonates (47%) had sub-therapeutic initial trough serum concentrations of vancomycin, whereas 22% had supra-therapeutic initial trough serum concentrations. In all patients doses were adjusted on basis of the initial trough concentration. In 40% (23/57) of the neonates the second trough concentration remained sub-therapeutic. MIC's were determined for 30 coagulase-negative Staphylococcus isolates obtained from 19 patients. Only 4 out of 19 subjects had a trough concentration greater than tenfold the MIC.
  
  
  CONCLUSIONS
  Forty-seven percent of the neonates had sub-therapeutic initial trough serum concentrations of vancomycin. The MIC-data indicate that the percentages of underdosed patients may be greater. It may be advisable to increase the lower limit of the therapeutic range for European neonates.
authors: Fleur S
authors: FS
authors: Sinkeler
authors: Timo R
authors: TR
authors: de Haan
authors: Caspar J
authors: CJ
authors: Hodiamont
authors: Yuma A
authors: YA
authors: Bijleveld
authors: Dasja
authors: D
authors: Pajkrt
authors: Academic Medical Center - Department of Clinical Pharmacy, PO Box 22660, 1100 DD Amsterdam, The Netherlands. r.mathot@amc.uva.nl.
authors: Ron A A
authors: RA
authors: Mathôt
mesh_terms: D061605:Administration, Intravenous; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D013210:Staphylococcus / Q000187:drug effects*; D016896:Treatment Outcome; D014640:Vancomycin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin