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

Exclusion Criteria

• •1. Has known or suspected new complicated staphylococcal infection at the time of enrollment.
• •2. Weigh ≥ 200 kg.
• •3. 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.
• •4. This criterion has been removed
• •5. Has a moribund clinical condition such that there is a high likelihood of death or cardiac surgery during the next three days.
• •6. Has shock or hypotension (supine systolic blood pressure \< 80 mmHg) or oliguria (urine output \< 20 mL/h) unresponsive to fluids or pressors within four hours.
• •7. Has received an investigational antibacterial agent with anti-staphylococcal activity within 30 days prior to randomization.
• •8. Has a documented history of significant allergy or intolerance to all protocol-approved antibiotics anticipated to be effective for their infection.
• •9. Has an infecting pathogen with confirmed reduced susceptibility to vancomycin (Minimum Inhibitory Concentrations (MIC) \> 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.
• •10. 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.
• •11. This criterion has been removed
• •12. Has previously known Human Immunodeficiency Virus (HIV) infection with a nadir CD4+ count of \<100 cells/mm3 within the past 12 months
• •13. Is considered unlikely to comply with study procedures or to return for scheduled post-treatment evaluations.
• •14. Is pregnant or trying to get pregnant, nursing, or lactating.
• •15. Has known or suspected septic arthritis, osteomyelitis, pneumonia or other metastatic focus of infection. CoNS patients with pneumonia and not being treated or anticipated to start treatment with antibiotics effective for the baseline infecting pathogen can be included
• •16. Has polymicrobial blood stream infection including at least one non-staphylococcal species, except AFTER consultation with the Clinical Medical Monitor at DCRI. Note that it is possible that a subject may not have a known polymicrobial bloodstream infection at the time of randomization, but additional pathogen(s) can subsequently be isolated from the initial blood culture. These patients will be eligible to remain in the trial. Please also note that patients with S. aureus plus CoNS will follow the treatment pathway for S. aureus.
• •17. This criterion has been removed.
• •18. Is hemodialysis dependent or has end stage renal disease (Creatinine Clearance (CrCl) \< 30 cc/min).
• •19. Developed Staphylococcus aureus blood stream infection within 72 hours of percutaneous coronary revascularization
• •20. Received of any of the following antibiotics for 7 or more of the 10 calendar days immediately preceding the calendar day that the initial positive blood culture was drawn:
• •2. If the staphylococcal isolate is known to be methicillin resistant: vancomycin; daptomycin; telavancin; tigecycline; linezolid (in either oral or IV administration), quinupristin/dalfopristin, dalbavancin, oritavancin, tedizolid, and ceftaroline.
• •Note: patients who have developed bacteremia after at least 7 days of prophylaxis with oral antibiotics have by definition failed prophylaxis and the oral antibiotic can be deemed non-effective for the index bacteremia. Oral antibiotics that have failed as prophylaxis in this manner will not be considered exclusionary or count towards the number of antibiotic days but must be stopped upon randomization
• •21. Has previously participated in this study.