Relationship between vancomycin tolerance and clinical outcomes in Staphylococcus aureus bacteraemia
Background: 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. Objectives: To compare the frequency of clinical failure between patients with VT and non-VT isolates in SAB. Methods: 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. Results: Of the 225 patients, 26.7% had VT isolates. VT was associated with clinical failure (48.0% overall) in unadjusted analysis [68.3% ( n =<I> 41/60) versus 40.6% ( n =<I> 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 =<I> 125, risk ratio, 1.67; 95% CI, 1.20-2.32; P =<I> 0.002); methicillin resistant ( n =<I> 100, risk ratio, 1.69; 95% CI, 1.14-2.51; P =<I> 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 =<I> 0.004). Conclusions: 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.
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