High-Dose Daptomycin Versus Linezolid for the Treatment of Vancomycin-Resistant Enterococcus faecium Bloodstream Infections: Role of Pharmacodynamic Target Attainment

Although high-dose daptomycin (≥8 mg/kg) and linezolid are recommended treatments for vancomycin-resistant Enterococci (VRE) bloodstream infection (BSI), direct comparisons and the impact of achieving prespecified pharmacokinetic/pharmacodynamic (PK/PD) target on outcomes remain unclear. We conducted a retrospective observational study in a single health system (January 2010-December 2021). Patients receiving daptomycin ≥8 mg/kg or linezolid for VRE BSI were included. The primary outcome was in-hospital mortality. The free area under the concentration-time curve to minimum inhibitory concentration ratio (fAUC/MIC) was estimated to assess its association with outcomes. Overall, 795 patients met the inclusion criteria. The overall mortality was 59.2 %. The linezolid group (n = 170) had a mortality of 44 %, and the daptomycin group (n = 625) mortality was 63 % (P < 0.001). Among daptomycin-treated patients, 528 had fAUC/MIC data and 114 achieved the PK/PD target. Mortality was 66 % for fAUC/MIC ≤75.07 (P < 0.001) and 49 % for fAUC/MIC >75.07 (P = 0.41), compared with linezolid group. In multivariable analysis, daptomycin was associated with higher mortality than linezolid (adjusted odds ratio [aOR], 2.00; P < 0.001). However, failing to achieve PK/PD target conferred significantly higher mortality than linezolid (aOR, 2.51; P < 0.001), whereas achieving the PK/PD target showed no difference (aOR, 0.97; P = 0.91). Even at doses ≥8 mg/kg, the efficacy for daptomycin is comparable to linezolid only when the PK/PD target is reached. Failing to achieve PK/PD target leads to worse outcomes, underscoring the importance of dose optimization and therapeutic drug monitoring.