Activity of Daptomycin or Linezolid in Combination with Rifampin or Gentamicin against Biofilm-Forming Enterococcus faecalis or E. faecium in an In Vitro Pharmacodynamic Model Using Simulated Endocardial Vegetations and an In Vivo Survival Assay Using Gal

Enterococci are the thirdmost frequent cause of infective endocarditis. A high-inoculum stationary-phase in vitro pharmacodynamic modelwith simulated endocardial vegetationswas used to simulate the humanpharmacokinetics of daptomycin at 6 or 10mg/kg of bodyweight/day or linezolid at 600mg every 12 h (q12h), alone or in combinationwith gentamicin at 1.3mg/kg q12h or rifampin at 300mg q8h or 900mg q24h. Biofilm-forming, vancomycin-susceptible Enterococcus faecalis and vancomycin-resistant Enterococ-cus faecium (vancomycin-resistant enterococcus [VRE]) strains were tested. At 24, 48, and 72 h, all daptomycin-containing regi-mens demonstrated significantly more activity (decline in CFU/g) than any linezolid-containing regimen against biofilm-form-ing E. faecalis. The addition of gentamicin to daptomycin (at 6 or 10 mg/kg) in the first 24 h significantly improved bactericidal activity. In contrast, the addition of rifampin delayed the bactericidal activity of daptomycin against E. faecalis, and the addition of rifampin antagonized the activities of all regimens against VRE at 24 h. Also, against VRE, the addition of gentamicin to lin-ezolid at 72 h improved activity and was bactericidal. Rifampin significantly antagonized the activity of linezolid against VRE at 72 h. In in vivo Galleria mellonella survival assays, linezolid and daptomycin improved survival. Daptomycin at 10 mg/kg im-proved survival significantly over that with linezolid against E. faecalis. The addition of gentamicin improved the efficacy of dap-tomycin against E. faecalis and those of linezolid and daptomycin against VRE. We conclude that in enterococcal infection mod