Treatment Algorithm to Reduce the Use of Vancomycin in Adults With Blood Stream Infection

Inclusion Criteria

• Provide signed and dated informed consent. The patient's legally authorized representative (LAR) can provide a signed informed consent for the patient if allowed by local Institutional Review Board/Ethics Committee (IRB/EC) policy.
• Is ≥ 18 yrs of age.
• If the subject has an intravenous catheter in place then the subject and his/her primary health care provider must agree to have the catheter removed within 5 days of the initial blood culture draw with the exception of those subjects who meet criteria for simple CoNS bacteremia as defined in Table 1. The catheter may be retained in those subjects with simple CoNS bacteremia.
• Has blood stream infection defined as at least one blood culture positive for S. aureus or CoNS. In most cases, vancomycin(or other study drug alternative) will have been started prior to randomization. Enrollment windows depend on speciation and clinical classification as follows:
• identification of CoNS and classification as simple per Table 1-must be randomized within 3 calendar days of the start of treatment effective for the baseline infecting pathogen
• identification of CoNS and classification as uncomplicated per Table 1 must be randomized within 4 calendar days of the start of treatment effective for the baseline infecting pathogen
• identification of S. aureus - must be randomized within 12 calendar days of the start of treatment effective for the baseline infecting pathogen
• This criterion has been removed
• Women of child bearing potential must have a negative urine and/or serum pregnancy test.
• All patients of reproductive potential must be abstinent or agree to use double-barrier contraception while receiving study (algorithm based or Standard of Care) therapy.

Exclusion Criteria

• Has known or suspected new complicated staphylococcal infection at the time of enrollment.
• Weigh ≥ 200 kg.
• Has non-removable intravascular foreign material at the time a positive blood culture was drawn (e.g., intracardiac pacemaker or cardioverter/defibrillator wires, hemodialysis access grafts, cardiac prosthetic valve, valvular support ring). Exception: coronary stents, inferior vena cava (IVC) filters in place > 6 weeks, patients with pacemakers whose baseline infecting pathogen is a CoNS, vascular stents in place for > 6 weeks, non-hemodialysis grafts in place >90 days and hemodialysis grafts not used within past 12 months and not previously infected are eligible for randomization. Arthroplasties and other extravascular devices, e.g. synthetic hernia repair mesh, and non-arthroplasty orthopedic prostheses including pins or plates, are acceptable as long as there are no signs or symptoms of foreign material-related infection at the time of randomization.
• This criterion has been removed
• Has a moribund clinical condition such that there is a high likelihood of death or cardiac surgery during the next three days.
• Has shock or hypotension (supine systolic blood pressure 2 µg/mL) if known. Note: If reduced susceptibility to vancomycin is discovered after enrollment, the patient will be treated with daptomycin (if pathogen is susceptible). Patient will remain in study as appropriate and be evaluated in the Intent to Treat (ITT) analysis, but will be excluded from Protocol Population (PP) analyses.
• For S. Aureus patients, is severely neutropenic (absolute neutrophil count < 0.100x103/mm3) or is anticipated to develop severe neutropenia (absolute neutrophil count < 0.100x103/ mm3) during the study treatment period due to prior or planned chemotherapy. CoNS patients with neutropenia are eligible to be enrolled.
• This criterion has been removed
• Has previously known Human Immunodeficiency Virus (HIV) infection with a nadir CD4+ count of <100 cells/mm3 within the past 12 months
• Is considered unlikely to comply with study procedures or to return for scheduled post-treatment evaluations.
• Is pregnant or trying to get pregnant, nursing, or lactating