Daptomycin as an Adjuvant Agent in the Treatment of Enterococcal Native Valve Endocarditis.
Condition: Endocarditis, Bacterial
MeSH terms: Endocarditis, Bacterial; Endocarditis
Intervention: Daptomycin
Intervention description: daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving for native valve enterococcal endocarditis
Intervention MeSH terms: Daptomycin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Enterococcus; Daptomycin; Endocarditis

Summary:

      The aim of this study is to determine the safety and efficacy of daptomycin when used as an
      adjuvant agent to standard care in the treatment of proven native valve Enterococcal
      endocarditis. Patients with this disease will be offered the option of receiving daptomycin
      at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already
      receiving. The hypothesis of this study is that daptomycin added to standard therapy for
      Enterococcal endocarditis is safe and efficacious.

      Patients who receive daptomycin + standard therapy will be compared to patients who receive
      standard therapy alone with respect to the following outcomes:

        1. Safety.

             1. The frequency of any Grade 3 or 4 toxicity (DAIDS scale) will be measured.

             2. The frequency of muscle toxicity or renal toxicity, as determined by predefined
                criteria.

        2. Efficacy.

             1. Clinical efficacy.

                  -  Time to clearance of bacteremia

                  -  Cure at 6 weeks following completion of antibiotic therapy

                  -  Mortality at 6 weeks following completion of antibiotic therapy

             2. Microbiologic efficacy.

                  -  Peak and trough serum bactericidal titers

                  -  The minimum bactericidal concentration of Enterococci to daptomycin

      We expect to enroll 40 patients over 2 years.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18 or over

          -  Definite Enterococcal endocarditis, as defined by modified Duke criteria

          -  Able to complete follow-up 3 and 6 weeks following completion of intravenous
             antibiotic therapy

        Exclusion Criteria:

          -  Pregnancy or breast feeding

          -  Creatine phosphokinase levels over two times the upper limit of normal

          -  Renal insufficiency or dialysis requirement.

          -  Presence of chronic indwelling bloodstream catheters or foreign body devices suspected
             as primary or secondary sites of enterococcal infection unamenable to removal or
             replacement

          -  Inability to discontinue or abstain from use of a HMG CoA reductase inhibitor during
             the study period.

          -  Hypersensitivity to any of the study medications.

          -  Any condition that, in the investigator's opinion, may interfere with protocol
             compliance including, but not limited to, active substance abuse and/or dementia.

          -  Prosthetic valve endocarditis