Daptomycin or linezolid versus vancomycin in the treatment of vancomycin-susceptible Enterococcus faecium bloodstream infections (SAVE study).

INTRODUCTION: Vancomycin is standard therapy for vancomycin-susceptible Enterococcus faecium bloodstream infection (VSE-BSI). Nephrotoxicity or patient-specific constraints may lead clinicians to use linezolid or daptomycin. METHODS: This retrospective study investigated the efficacy and safety of linezolid/daptomycin (n=83) versus vancomycin (n=134) in patients with VSE-BSI in 3 French hospitals (November 2015-April 2023). The primary outcome was treatment failure, defined as a composite of clinical failure, microbiological failure, 30-day all-cause mortality, and 90-day VSE-BSI recurrence. Risk factors for treatment failure and association between treatment and 30-day mortality were assessed. RESULTS: Overall treatment failure was 54% (52% vs 57%; p=0.49). Linezolid/daptomycin was not associated with higher risk of treatment failure (odds ratio (OR) 1.22, 95% confidence interval (CI) [0.57-2.62], p=0.61), unlike sepsis (OR 3.11, 95% CI [1.12-8.59], p=0.03) and baseline C-reactive protein (OR 1.01, 95% CI [1.00-1.01], p=0.01). The 30-day mortality was significantly higher in the linezolid/daptomycin group (45% vs 28%; risk ratio 1.57, 95% CI [1.10-2.25], p=0.02) but not after adjustment for confounding factors (hazard ratio 0.6, 95% CI [0.40-1.00], p=0.07). CONCLUSION: Linezolid or daptomycin was not independently associated with treatment failure. However, residual confounding and heterogeneity between these agents preclude conclusions of equivalence or causality. Linezolid or high-dose daptomycin may be considered when vancomycin is unsuitable.