Inclusion Criteria:

1. 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.

2. Is ≥ 18 yrs of age.

3. 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 48 hours
of enrollment 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.

4. Has blood stream infection defined as at least two blood culture samples of which at
least one is positive for S. aureus or CoNS, obtained within 2 calendar days prior to
enrollment (Day -2 or Day -1). In most cases, vancomycin (or other study drug
alternative) will have been started prior to enrollment. Among patients being
evaluated for study enrollment prior to speciation of the bacteria isolated from
blood cultures, a Gram stain result of blood culture contents demonstrating Gram
positive cocci in clusters will be acceptable. Patients with community-acquired
infections may be included unless there is more than one positive blood culture at
the time of enrollment. The rationale being that these patients are very likely to
have complicated staphylococcal infection.

5. Subject requires intravenous antibiotic therapy in the opinion of his/her physician.

6. Women of child bearing potential must have a negative urine and/or serum pregnancy
test.

7. 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:

1. Has known or suspected new complicated staphylococcal infection at the time of
enrollment.

2. Weighs ≥ 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), which
was not removed within 48 hours of enrollment. Exception: patients with epicardial
pacemakers, vascular stents and non-hemodialysis grafts in place >90 days are
eligible for enrollment. Arthroplasties and other extravascular devices are
acceptable as long as there are no signs or symptoms of foreign material-related
infection at the time of enrollment.

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 drug within 30 days of study entry.

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). 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. 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.

11. This criterion has been removed 12. Has previously known Human Immunodeficiency
Virus (HIV) infection with a nadir CD4+ count of 100 cells/mm3 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.

16. Has polymicrobial blood stream infection including at least one non-staphylococcal
species. Note that it is possible that a subject may not have a known polymicrobial
bloodstream infection at the time of enrollment, 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:

- If methicillin susceptibility of the isolate is unknown at the time of enrollment:
vancomycin; daptomycin; telavancin; tigecycline; linezolid (in either oral or
intravenous administration); quinupristin/dalfopristin; piperacillin/tazobactam;
nafcillin; oxacillin; cloxacillin; cefazolin; ceftriaxone; ceftaroline; levofloxacin
or equivalent fluoroquinolone (in either oral or intravenous administration) Note:
ciprofloxacin is not an exclusion criteria.

- If the staphylococcal isolate is known to be methicillin resistant: vancomycin;
daptomycin; telavancin; tigecycline; linezolid (in either oral or intravenous
administration), quinupristin/dalfopristin, ceftaroline.

21. Has previously participated in this study.