Relationship between vancomycin tolerance and clinical outcomes in Staphylococcus aureus bacteraemia

<span class="paragraphSection"><strong>Background:</strong> Previous data have demonstrated the clinical importance of vancomycin MIC values in <span style="font-style:italic;">Staphylococcus aureus</span> bacteraemia (SAB); however, the impact of vancomycin tolerance (VT) is unknown.<strong>Objectives:</strong> To compare the frequency of clinical failure between patients with VT and non-VT isolates in SAB.<strong>Methods:</strong> 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.<strong>Results:</strong> Of the 225 patients, 26.7% had VT isolates. VT was associated with clinical failure (48.0% overall) in unadjusted analysis [68.3% (<span style="font-style:italic;">n </span>=<span style="font-style:italic;"> </span>41/60) versus 40.6% (<span style="font-style:italic;">n </span>=<span style="font-style:italic;"> </span>67/165); <span style="font-style:italic;">P </span><<span style="font-style:italic;"> </span>0.001] and this relationship persisted in multivariable analysis (adjusted risk ratio, 1.74; 95% CI, 1.36-2.24; <span style="font-style:italic;">P </span><<span style="font-style:italic;"> </span>0.001). The association between VT and clinical failure was also consistent within strata of methicillin susceptibility [methicillin susceptible (<span style="font-style:italic;">n </span>=<span style="font-style:italic;"> </span>125, risk ratio, 1.67; 95% CI, 1.20-2.32; <span style="font-style:italic;">P </span>=<span style="font-style:italic;"> </span>0.002); methicillin resistant (<span style="font-style:italic;">n </span>=<span style="font-style:italic;"> </span>100, risk ratio, 1.69; 95% CI, 1.14-2.51; <span style="font-style:italic;">P </span>=<span style="font-style:italic;"> </span>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; <span style="font-style:italic;">P </span>=<span style="font-style:italic;"> </span>0.004).<strong>Conclusions:</strong> 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.</span>

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