title: The Mark Coventry Award: Higher tissue concentrations of vancomycin with low-dose intraosseous regional versus systemic prophylaxis in TKA: a randomized trial.
abstract: BACKGROUND
  In response to increasing antibiotic resistance, vancomycin has been proposed as an alternative prophylactic agent in TKA. However, vancomycin requires a prolonged administration time, risks promoting further antibiotic resistance, and can cause systemic toxicity. Intraosseous regional administration (IORA) is known to achieve markedly higher antibiotic concentrations than systemic administration and may allow the use of a lower vancomycin dose.
  
  
  OBJECTIVE
  We assessed whether low-dose IORA vancomycin can achieve tissue concentrations equal or superior to those of systemic administration in TKA and compared complications between patients treated with IORA and intravenous vancomycin.
  
  
  METHODS
  We randomized 30 patients undergoing primary TKA to receive 250 or 500 mg vancomycin via IORA or 1 g via systemic administration. IORA was performed as a bolus injection into a tibial intraosseous cannula below an inflated thigh tourniquet immediately before skin incision. Subcutaneous fat and bone samples were taken during the procedure and antibiotic concentrations measured.
  
  
  RESULTS
  The overall mean tissue concentration of vancomycin in subcutaneous fat was 14 μg/g in the 250-mg IORA group, 44 μg/g in the 500-mg IORA group, and 3.2 μg/g in the systemic group. Mean concentrations in bone were 16 μg/g in the 250-mg IORA group, 38 μg/g in the 500-mg IORA group, and 4.0 μg/g in the systemic group. One patient in the systemic group developed red man syndrome during infusion.
  
  
  CONCLUSIONS
  Low-dose IORA vancomycin results in tissue concentrations equal or superior to those of systemic administration. IORA optimizes timing of vancomycin administration, and the lower dose may reduce the risk of systemic side effects while providing equal or enhanced prophylaxis in TKA.
authors.affiliation: Department of Orthopaedics, North Shore Hospital, Private Bag 93-503, Takapuna, Auckland, 0740, New Zealand, simonwyoung@gmail.com.
authors.forename: Simon W
authors.initials: SW
authors.lastname: Young
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Freeman
authors.forename: John
authors.initials: J
authors.lastname: Mutu-Grigg
authors.forename: Paul
authors.initials: P
authors.lastname: Pavlou
authors.forename: Grant A
authors.initials: GA
authors.lastname: Moore
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis / Q000379:methods*; D019645:Arthroplasty, Replacement, Knee / Q000379:methods*; D001363:Awards and Prizes; D005260:Female; D006801:Humans; D017148:Infusions, Intraosseous; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D014640:Vancomycin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin