title: Relationship between vancomycin tolerance and clinical outcomes in Staphylococcus aureus bacteraemia.
abstract: Previous data have demonstrated the clinical importance of vancomycin MIC values in Staphylococcus aureus bacteraemia (SAB); however, the impact of vancomycin tolerance (VT) is unknown.
  
  
  
  To compare the frequency of clinical failure between patients with VT and non-VT isolates in SAB.
  
  
  
  This was a retrospective cohort study of patients with SAB, excluding treatment <48 h or polymicrobial bacteraemia. The primary outcome was clinical failure (composite of 30 day mortality, non-resolving signs and symptoms, and 60 day recurrence). Vancomycin MIC and MBC were determined by broth microdilution. The association between VT (MBC/MIC ≥32) and clinical failure was evaluated by multivariable Poisson regression.
  
  
  
  Of the 225 patients, 26.7% had VT isolates. VT was associated with clinical failure (48.0% overall) in unadjusted analysis [68.3% (n = 41/60) versus 40.6% (n = 67/165); P < 0.001] and this relationship persisted in multivariable analysis (adjusted risk ratio, 1.74; 95% CI, 1.36-2.24; P < 0.001). The association between VT and clinical failure was also consistent within strata of methicillin susceptibility [methicillin susceptible (n = 125, risk ratio, 1.67; 95% CI, 1.20-2.32; P = 0.002); methicillin resistant (n = 100, risk ratio, 1.69; 95% CI, 1.14-2.51; P = 0.010)]. Among methicillin-susceptible SAB cases treated with β-lactam therapy, VT remained associated with clinical failure (risk ratio, 1.77; 95% CI, 1.19-2.61; P = 0.004).
  
  
  
  VT was associated with clinical failure in SAB, irrespective of methicillin susceptibility or definitive treatment. VT may decrease the effectiveness of cell-wall-active therapy or be a surrogate marker of some other pathogen-specific factor associated with poor outcomes. Future research should evaluate if bactericidal non-cell-wall-active agents improve outcomes in VT SAB.
authors.affiliation: Department of Pharmacy Practice, University of Kansas School of Pharmacy, 2010 Becker Drive, Lawrence, KS, USA.|Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, USA.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Britt
authors.affiliation: Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY, USA.
authors.forename: Nimish
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, USA.
authors.forename: Theresa I
authors.initials: TI
authors.lastname: Shireman
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, USA.
authors.forename: Wissam I
authors.initials: WI
authors.lastname: El Atrouni
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, USA.
authors.forename: Rebecca T
authors.initials: RT
authors.lastname: Horvat
authors.affiliation: Department of Pharmacy Practice, University of Kansas School of Pharmacy, 2010 Becker Drive, Lawrence, KS, USA msteed@kumc.edu.
authors.forename: Molly E
authors.initials: ME
authors.lastname: Steed
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D016106:Methicillin Resistance; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D062606:Tertiary Care Centers; D017211:Treatment Failure; D014640:Vancomycin / Q000627:therapeutic use*; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin