title: Are bone and serum cefazolin concentrations adequate for antimicrobial prophylaxis?
abstract: BACKGROUND
  Antimicrobial prophylaxis is considered beneficial for preventing surgical-site infections in clean orthopaedic surgery. However, whether tissue concentrations of cefazolin achieve the minimum inhibitory concentration for the targeted contaminants have yet to be clarified.
  
  
  OBJECTIVE
  We asked whether 2 g of cefazolin would enable effective serum and bone concentrations relative to the current minimum inhibitory concentration for cefazolin-resistant coagulase-negative Staphylococci and methicillin-sensitive Staphylococcus aureus.
  
  
  METHODS
  We enrolled 43 patients (THA, n = 16; TKA, n = 27) scheduled for primary THAs and primary TKAs. Subjects were given 2 g of cefazolin intravenously before incision. One blood sample and two bone samples were collected from each subject before tourniquet deflation before any additional dose. All samples were assayed at the same laboratory. Minimum inhibitory concentration values were defined based on nationwide surveys.
  
  
  RESULTS
  Mean (± standard deviation) serum concentration was 170.3 ± 51.3 μg/mL (range, 99.3-370.3 μg/mL). Mean bone concentration was 32.3 ± 15.2 μg/g (range, 11.4-70.0 μg/g) in THA, and 16.0 ± 10.4 μg/g (range, 6.3-46.3 μg/g) in TKA. All serum and bone concentrations exceeded the minimum inhibitory concentration for methicillin-sensitive S. aureus, but some serum levels were marginal and no bone levels exceeded the minimum inhibitory concentration for cefazolin-resistant coagulase-negative Staphylococcus.
  
  
  CONCLUSIONS
  Our data suggest intravenous administration of 2 g of cefazolin achieves the minimum inhibitory concentration for methicillin-sensitive S. aureus in serum and bone, but not the minimum inhibitory concentration for cefazolin-resistant coagulase-negative Staphylococcus in bone, resulting in a potential risk of deep surgical site infections in THAs and TKAs.
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. forpatients2008@gmail.com
authors.forename: Koji
authors.initials: K
authors.lastname: Yamada
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tokimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okazaki
authors.forename: Sakae
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D019072:Antibiotic Prophylaxis; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D001842:Bone and Bones / Q000378:metabolism*; D002437:Cefazolin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008826:Microbial Sensitivity Tests; D015610:Serum Bactericidal Test; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013530:Surgical Wound Infection / Q000517:prevention & control
chemical_list: D000900:Anti-Bacterial Agents; D002437:Cefazolin