Relationship between vancomycin tolerance and clinical outcomes in Staphylococcus aureus bacteraemia

Abstract

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=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). 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 noncell- wall-active agents improve outcomes in VT SAB.