title: Single- versus multiple-dose antibiotic prophylaxis in the surgical treatment of closed fractures: a meta-analysis.
abstract: OBJECTIVE
  The use of prophylactic antibiotics in the surgical treatment of closed long bone fractures is well established. The duration and dosage of prophylaxis, however, vary significantly among surgeons. A systematic review and meta-analysis were performed to determine if multiple-dose perioperative antibiotic prophylaxis is more effective than a single preoperative dose in the prevention of surgical wound infections during the treatment of closed long bone fractures.
  
  
  METHODS
  Articles were identified by searching the following medical databases: Medline, Medline In Process & Other Non-indexed Citations, Embase, CENTRAL, and the Cochrane Database of Systematic Reviews. Relevant conference proceedings and the reference section of selected manuscripts were also searched for additional studies.
  
  
  METHODS
  Studies were included if they were prospective randomized controlled trials of patients with closed fractures treated with surgical fixation or arthroplasty. The interventions must have directly compared a single preoperative prophylactic dose to a multiple-dose perioperative strategy. Studies were excluded if they involved open fractures.
  
  
  METHODS
  The demographic information, prophylaxis strategy, wound infection rate, and risk ratio were extracted from each article.
  
  
  RESULTS
  Seven trials and 3,808 patients were pooled using a random effects model. When compared to a regimen of multiple doses of prophylactic antibiotics, administration of a single preoperative dose has a risk ratio of 1.24 (95% CI 0.60-2.60). The pooled risk difference between the 2 strategies is 0.005 (95% CI -0.011-0.021). Neither result is significant.
  
  
  CONCLUSIONS
  In the setting of closed long bone fractures, the pooled results failed to demonstrate superiority of multiple-dose prophylaxis over a single-dose strategy. The pooled estimates suggest that surgical wound infections are relatively rare events and that any potential difference in infection rates between prophylaxis strategies is likely quite small. However, because the confidence interval surrounding the pooled risk ratio spans 1.0 by such a large amount, we are unable to definitively recommend a preferred dosing regimen to prevent surgical wound infections. Although future research is required to ensure our prophylaxis decisions continue to be evidence based and cost-effective, it is unlikely that a single clinical trial will be able to provide the answer. The use of other quantitative methods, such as cost-effectiveness analysis, may be helpful in modeling an optimal prophylaxis strategy.
authors.affiliation: Department of Orthopaedics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Gerard P
authors.initials: GP
authors.lastname: Slobogean
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Kennedy
authors.forename: Darin
authors.initials: D
authors.lastname: Davidson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Brien
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D019072:Antibiotic Prophylaxis / Q000379:methods*; D004334:Drug Administration Schedule; D005596:Fractures, Closed / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D016017:Odds Ratio; D019637:Orthopedic Procedures / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents