Abstract Objectives Among patients with daptomycin-resistant and vancomycin-resistant Enterococcus faecium bloodstream infection (BSI), the optimal definitive therapy is uncertain. We estimated the dose effect of daptomycin (≥11 mg/kg versus 8 to 11 mg/kg) on 28-day mortality and exploratorily described outcomes in patients treated with linezolid. Methods Adults with VRE BSI who received linezolid or daptomycin ≥8 mg/kg were included. Post hoc daptomycin MICs were determined by Sensititre broth microdilution (BMD), and episodes with MIC ≥8 mg/L were analyzed. The primary outcome was 28-day in-hospital mortality. Results Among 130 patients with daptomycin-resistant VRE BSI, 110 received daptomycin and 20 received linezolid. Within the daptomycin group, 28-day mortality was 55.1% (43/78) with daptomycin 8 to 11 mg/kg and 34.4% (11/32) with daptomycin ≥11 mg/kg. In adjusted analysis, daptomycin 8 to 11 mg/kg was associated with higher mortality than daptomycin ≥11 mg/kg adjusted odds ratio (aOR) 3.11, 95% CI 1.13 to 8.56, P = 0.03. Among isolates with daptomycin MIC = 8 mg/L, 28-day mortality was 54.9% in patients treated with daptomycin 8 to 11 mg/kg versus 29.6% treated with daptomycin ≥11 mg/kg (P = 0.04); no benefit was seen for MIC ≥16 mg/L (P 0.99). 28-day mortality was 49.1% (54/110) with daptomycin and 35.0% (7/20) with linezolid (P = 0.33); linezolid was not associated with lower mortality than daptomycin in adjusted analysis (P = 0.48). Conclusions In daptomycin-resistant VRE BSI, daptomycin ≥11 mg/kg was associated with lower 28-day mortality than daptomycin 8 to 11 mg/kg, particularly at MIC = 8 mg/L. Comparisons with the small linezolid arm are exploratory and underpowered. Larger studies are needed to confirm these hypothesis-generating findings.
Lin et al. (Thu,) studied this question.