Comparative Outcomes of Daptomycin and Linezolid in Vancomycin-resistant Enterococcal Intra-abdominal Infections with Bacteremia

• The medicinal options to treat intraabdominal infection (IAI) caused by vancomycin-resistant enterococci (VRE) remain limited. • This study provides evidence that daptomycin is comparable with linezolid to treat VRE-IAI with bloodstream infection, and daptomycin ≥11 mg/kg is associated with better survival. Vancomycin-resistant enterococci (VRE) are pathogenic in intra-abdominal infections (IAI). Although daptomycin (8–12 mg/kg) is effective for VRE bloodstream infections (BSI), evidence supporting its use in VRE-IAI remains limited. We conducted a multicenter observational study. Between April 2010 and October 2024, we screened all patients with VRE-BSI and included those with a documented VRE-IAI treated with daptomycin or linezolid. Limiting enrollment to patients with concurrent bloodstream infections reduced misclassification bias. The primary outcome was 28‑day in‑hospital mortality. Of 184 patients included, 149 received daptomycin and 35 received linezolid. Most patients (98.3%) underwent source control procedures. A total of 96 patients (52.2%) had hepatobiliary IAI, while 88 (47.8%) had non-biliary IAI. The 28-day mortality did not differ significantly between daptomycin and linezolid groups (29.5% vs. 37.1%; P =0.42). Multivariable logistic regression identified the independent predictors of mortality including higher Pitt bacteremia score (adjusted odds ratio 95% confidence interval, 1.22 1.06–1.41; P =0.006), lower platelet count (0.97 0.94–0.99; P =0.02), and malignancy (2.41 1.10–5.25; P =0.03). Daptomycin was not associated with increased mortality compared with linezolid (adjusted odds ratio 95% confidence interval, 0.63 0.28–1.44; P =0.27). Daptomycin ≥11 mg/kg was linked to reduced mortality (adjusted odds ratio 95% confidence interval, 0.29 0.09–0.91; P =0.03), whereas daptomycin 8–11 mg/kg showed no significant difference (0.79 0.34–1.85; P =0.59). Findings were consistent in augmented inverse probability weighting analysis. Daptomycin is comparable with linezolid for treating VRE-IAI and BSI, with daptomycin ≥11 mg/kg associated with improved survival. Further investigations are warranted given a small sample size.