Bhavarth S. Shukla, Samuel Shelburne, Katherine Reyes, Mini Kamboj, Jessica D. Lewis, Sandra L. Rincon, Jinnethe Reyes, Lina P. Carvajal, Diana Panesso, Costi D. Sifri, Marcus J. Zervos, Eric G. Pamer, Truc T. Tran, Javier Adachi, Jose M. Munita, Rodrigo Hasbun, Cesar A. Arias

 Daptomycin has become a key front-line antibiotic for multidrug-resistantE. faeciumbloodstream infections (BSIs). We previously showed thatE. faeciumstrains with daptomycin MICs in the higher end of susceptibility frequently harbor mutations in genes associated with daptomycin resistance. We postulate that patients withE. faeciumBSIs exhibiting daptomycin MICs of 3-4 µg/mL and treated with daptomycin are more likely to have worse clinical outcomes than those exhibiting daptomycin MICs≤2 µg/mL.  We conducted a multicenter (4 sites) retrospective cohort study (2010 - 2015) that included adult patients withE. faeciumBSI for whom initial isolates, follow-up blood culture data, and daptomycin administration data were available. A central laboratory performed standardized daptomycin MIC testing for all isolates. The primary outcome was microbiologic failure, defined as clearance of bacteremia occurring ≥4 days after the index blood culture. The secondary outcome was all-cause in-hospital mortality.  A total of 62 patients were included. Thirty-one patients (50%) were infected with isolates exhibiting daptomycin MICs of 3-4 µg/mL. Overall, 34 (55%) patients had microbiologic failure and 25 (40%) died during hospitalization. On a multivariate logistic regression model, daptomycin MICs of 3-4 µg/mL (OR 4.7 [1.37-16.12], p=0.014) and immunosuppression (OR 5.32 [1.20-23.54], p=0.028) were significantly associated with microbiologic failure, while initial daptomycin dose of ≥8 mg/kg was not significantly associated with evaluated outcomes.  Daptomycin MICs of 3-4 µg/mL in the initialE. faeciumblood isolate predicted microbiological failure of DAP therapy suggesting that modification in the daptomycin breakpoint for enterococci should be considered.