title: Association between the AUC0-24/MIC Ratio of Vancomycin and Its Clinical Effectiveness: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  A target AUC0-24/MIC ratio of 400 has been associated with its clinical success when treating Staphylococcus aureus infections but is not currently supported by state-of-the-art evidence-based research.
  
  
  OBJECTIVE
  This current systematic review aimed to evaluate the available evidence for the association between the AUC0-24/MIC ratio of vancomycin and its clinical effectiveness on hospitalized patients and to confirm the existing target value of 400.
  
  
  METHODS
  PubMed, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were systematically searched. Manual searching was also applied. Both RCTs and observational studies comparing the clinical outcomes of high AUC0-24/MIC groups versus low AUC0-24/MIC groups were eligible. Two reviewers independently extracted the data. The primary outcomes were mortality and infection treatment failure. Risk ratios (RRs) with 95% confidence intervals (95%CIs) were calculated.
  
  
  RESULTS
  No RCTs were retrieved. Nine cohort studies were included in the meta-analysis. Mortality rates were significantly lower in high AUC0-24/MIC groups (RR = 0.47, 95%CI = 0.31-0.70, p<0.001). The rates of infection treatment failure were also significantly lower in high AUC/MIC groups and were consistent after correcting for heterogeneity (RR = 0.39, 95%CI = 0.28-0.55, p = 0.001). Subgroup analyses showed that results were consistent whether MIC values were determined by broth microdilution (BMD) method or Etest method. In studies using the BMD method, breakpoints of AUC0-24/MIC all fell within 85% to 115% of 400.
  
  
  CONCLUSIONS
  This meta-analysis demonstrated that achieving a high AUC0-24/MIC of vancomycin could significantly decrease mortality rates by 53% and rates of infection treatment failure by 61%, with 400 being a reasonable target.
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.|Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Men
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.|Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Hui-Bo
authors.initials: HB
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.
authors.forename: Suo-Di
authors.initials: SD
authors.lastname: Zhai
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.
authors.forename: Rong-Sheng
authors.initials: RS
authors.lastname: Zhao
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D006801:Humans; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy*; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin