title: Association between vancomycin minimum inhibitory concentration and mortality among patients with Staphylococcus aureus bloodstream infections: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Staphylococcus aureus bacteremia (SAB) is a worldwide problem. It is unclear whether higher-vancomycin minimum inhibitory concentration (MIC) is associated with mortality. This potential association has direct consequences for patients and public health.
  
  
  METHODS
  PubMed, Embase, the Cochrane Library, Evidence-based Medicine BMJ, and the American College of Physicians Journal Club were searched from inception through April 2014.
  
  
  METHODS
  Studies reporting mortality and vancomycin MIC in patients with SAB were included.
  
  
  METHODS
  Two authors performed the literature search and the study selection separately. Random-effects modeling was used for all analyses.
  
  
  METHODS
  All-cause mortality.
  
  
  RESULTS
  Among 38 included studies that involved 8291 episodes of SAB, overall mortality was 26.1%. The estimated mortality was 26.8% among SAB episodes (n = 2740) in patients with high-vancomycin MIC (≥1.5 mg/L) compared with 25.8% mortality among SAB episodes (n = 5551) in patients with low-vancomycin MIC (<1.5 mg/L) (adjusted risk difference [RD], 1.6% [95% CI, -2.3% to 5.6%]; P = .43). For the highest-quality studies, the estimated mortality was 26.2% among SAB episodes (n = 2318) in patients with high-vancomycin MIC compared with 27.8% mortality among SAB episodes (n = 4168) in patients with low-vancomycin MIC (RD, 0.9% [95% CI, -2.9% to 4.6%]; P = .65). In studies that included only methicillin-resistant S aureus infections (n = 7232), the mortality among SAB episodes (n = 2384) in patients with high-vancomycin MIC was 27.6% compared with mortality of 27.4% among SAB episodes (n = 4848) in patients with low-vancomycin MIC (adjusted RD, 1.6% [95% CI, -2.3% to 5.5%]; P = .41). No significant differences in risk of death were observed in subgroups with high-vancomycin MIC vs low-vancomycin MIC values across different study designs, microbiological susceptibility assays, MIC cutoffs, clinical outcomes, duration of bacteremia, previous vancomycin exposure, and treatment with vancomycin.
  
  
  CONCLUSIONS
  In this meta-analysis of SAB episodes, there were no statistically significant differences in the risk of death when comparing patients with S aureus exhibiting high-vancomycin MIC (≥1.5 mg/L) to those with low-vancomycin MIC (<1.5 mg/L), although the findings cannot definitely exclude an increased mortality risk. These findings should be considered when interpreting vancomycin susceptibility and in determining whether alternative antistaphylococcal agents are necessary for patients with SAB with elevated but susceptible vancomycin MIC values.
authors.affiliation: Department of Internal Medicine, Division of Infectious Disease, University of Nebraska Medical Center, Omaha.
authors.forename: Andre C
authors.initials: AC
authors.lastname: Kalil
authors.affiliation: Department of Internal Medicine, Division of Infectious Disease, University of Nebraska Medical Center, Omaha.
authors.forename: Trevor C
authors.initials: TC
authors.lastname: Van Schooneveld
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Fey
authors.affiliation: Department of Internal Medicine, Division of Infectious Disease, University of Nebraska Medical Center, Omaha.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Rupp
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000401:mortality; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use*; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin