Linezolid versus daptomycin for VRE bloodstream infections in patients with malignancy: The impact of neutropenia on outcomes.

Objectives: Vancomycin-resistant enterococcal bloodstream infections (VRE-BSIs) carry high mortality in patients with malignancy. While neutropenia is a known risk factor for mortality in patients with malignancy and BSI, its impact on the effectiveness of daptomycin and linezolid in VRE-BSI is not well defined.

Methods: We conducted a multicenter cohort study of hospitalized patients aged ≥18 years with malignancy and VRE-BSI between 2010 and 2021. Eligible patients received linezolid or high-dose daptomycin (≥8 mg/kg). Those with pneumonia or Enterococcus species other than E. faecium were excluded. Only the first VRE-BSI episode per patient was analyzed. The primary outcome was 14-day mortality, assessed using multivariable logistic regression.

Results: A total of 474 patients were included (linezolid, n = 90; daptomycin, n = 384); 128 (27.0 %) had neutropenia. The 14-day mortality was 32.9 % (156/474). Mortality was higher in neutropenic than non-neutropenic patients (45/128 [35.2 %] vs. 111/346 [32.1 %]; P = 0.005). Among neutropenic patients, mortality was 6/8 (75.0 %) with linezolid and 49/120 (40.8 %) with daptomycin; in non-neutropenic patients, mortality was 16/82 (19.5 %) and 85/264 (32.2 %), respectively. In multivariable analysis, linezolid use in neutropenic patients was associated with higher mortality (aOR 8.48; 95 % CI, 1.40-51.30; P = 0.02).

Conclusions: Neutropenia was associated with worse outcomes in patients with VRE-BSI, and linezolid-treated neutropenic patients showed higher mortality in this cohort. These findings should be interpreted cautiously given the small sample size and residual confounding. High-dose daptomycin may be considered, particularly in neutropenic patients, but confirmatory studies are needed.