Risk Factors and Outcomes of Vancomycin-Resistant Enterococcus faecium Bloodstream Infection in Hematologic Malignancies and Stem Cell Transplant Recipients: A Case-Control Study

Abstract Background Vancomycin-resistant Enterococcus faecium (VREfm) bloodstream infection (BSI) represents a growing challenge in hematology-oncology settings. This study aimed to characterize the epidemiology, risk factors, and prognostic impact of VREfm BSI within a mixed adult hematology-oncology and transplant unit. Methods We conducted a retrospective matched case-control study (2014–2024). Multivariable conditional logistic regression identified factors associated with VREfm BSI, and restricted cubic spline (RCS) models assessed nonlinear exposure-response relationships between antimicrobial classes and VREfm BSI. Survival was analyzed using Kaplan-Meier curves and Cox proportional hazards regression. Results VREfm BSI incidence rose from 0.02 to 0.07 per 1,000 person-days (2014–2018 vs 2019–2024). A composite high-risk phenotype comprising recipients of allogeneic stem cell transplant and/or AML (adjusted OR [aOR], 3.90; 95% CI, 1.87–8.15; p < 0.001) and ICU admission (aOR, 5.63; 95% CI, 2.15–14.78; p < 0.001), were independently associated with VREfm BSI. Cumulative days of carbapenems (aOR, 1.09/day; 95% CI, 1.02–1.17; p = 0.013), beta-lactam/beta-lactamase inhibitors (aOR, 1.09/day; 95% CI, 1.02–1.16; p = 0.006), and systemic antifungals (aOR, 1.12/day; 95% CI, 1.03–1.22; p = 0.009) exhibited duration-dependent associations. RCS models demonstrated a nonlinear, duration-dependent association with cumulative antibiotic exposure, including anti-anaerobic agents (p < 0.001). VREfm BSI was associated with increased mortality (adjusted hazard ratio, 2.09; 95% CI, 1.63–2.66; p <0.001). Conclusion VREfm BSI reflects the interplay between host susceptibility and nonlinear, duration- and spectrum-dependent antibiotic pressure. This underscores the significance of implementing antimicrobial stewardship strategies as a potential intervention to mitigate risk.