DOTS: Dalbavancin as an Option for Treatment of Staphylococcus Aureus Bacteremia

Inclusion Criteria

• Written informed consent obtained from the patient or legally authorized representative before the initiation of any study-specific procedures.
• Patients > / = to 18 years old.
• A diagnosis of complicated Staphylococcus aureus (either Methicillin-sensitive Staphylococcus aureus or Methicillin-resistant Staphylococcus aureus) bloodstream infection.
• Treated with effective antibiotic therapy for at least 72 hours (maximum 10 days).*

*Ten consecutive days prior to randomization is the maximum allowed treatment duration. If a subject has received intermittent or incomplete therapy earlier in the treatment course for this episode of S. aureus bacteremia, then discuss with the protocol PI and DMID Medical Officer prior to enrollment.

• Subsequent defervescence for at least 24 hours and clearance of bacteremia from the qualifying pathogen (at Screening), with negative blood culture incubated for at least 48 hours.**

**Two negative blood cultures incubated for 48 hours are preferred. However, if only a single blood culture set is drawn, no growth at 48 hours will be considered adequate to demonstrate clearance. If more than one culture set is drawn, all must show no growth at 48 hours to be considered evidence of clearance (e.g., 1 of 2 positive cultures would still be considered as ongoing bacteremia).

• Provider willing to treat with either dalbavancin for two doses, or standard of care intravenous monotherapy for at least 4 and no more than 8 weeks from randomization.
• Patients must be willing and able, if discharged, to return to the hospital or designated clinic for scheduled treatment, laboratory tests, or other procedures as required by the protocol.
• According to the site Principal Investigator or sub-investigator assessment, patients must be expected to survive with appropriate antibiotic therapy and appropriate supportive care throughout the study.

Exclusion Criteria

• Uncomplicated bacteremia.*

*Uncomplicated Staphylococcus aureus bacteremia is defined as all of the following: exclusion of endocarditis by echocardiography; catheter-associated bacteremia and removal of catheter; no implanted prostheses; follow-up blood cultures drawn within 48 hours after initial set that do not grow screening pathogen and all follow-up blood cultures thereafter do not grow the screening pathogen; defervescence within 72 hours of initiating effective therapy; and no evidence of metastatic sites of infection.

• Infectious Central Nervous System events, including septic emboli, ischemic or hemorrhagic stroke, epidural abscess, or meningitis (prior/unrelated Central Nervous System events are not exclusion criteria).
• Known or suspected left-sided endocarditis or presence of a perivalvular abscess.
• Planned right-sided valve replacement surgery in the first 3 days following randomization.
• Presence of prosthetic heart valve, cardiac device** UNLESS removal is planned within 4 days post-randomization.

**Implantable cardioverter defibrillator (ICD), permanent pacemaker, valve support ring, ventricular assist device (VAD).

• Presence of intravascular graft or intravascular material*** UNLESS removal is planned within 4 days post-randomization

***Excluding cardiac stents, inferior vena cava filters in place for >6 weeks, vascular stents in place for >6 weeks, non-hemodialysis grafts in place >90 days, and hemodialysis grafts not used within the past 12 months and not previously infected. A fistula constructed from native veins or a biologic vascular graft (without synthetic graft material) does not count as intravascular graft/material.

• Infected prosthetic joint or extravascular hardware UNLESS removal is planned within 4 days post-randomization OR hardware was placed >60 days before bacteremia and clinically appears uninfected.
• Polymicrobial bacteremia unless the non-Staphylococcus aureus organism is a contaminant.****

****Note: If a gram-negative bacteremia or fungemia develops after the