Daptomycin Versus Vancomycin in Participants With Skin Infections Due to MRSA

Eligible participants will be recruited within 24 hours of hospital admission for cSSSI due
to suspected or documented Methicillin-resistant Staphylococcus Aureus (MRSA), and who are
anticipated to require IV antibiotics effective against MRSA and at least 3 days of
hospitalization for management of cSSSI. The primary objective is to compare
infection-related hospital length of stay between participants treated with daptomycin and
vancomycin. Secondary objectives were to compare participant reported outcomes (pain symptoms
and Health Related Quality of Life), 30 day cSSSI-related hospital readmission rates, and
cSSSI-related medical resource utilization and costs between participants treated with
daptomycin and vancomycin.

Inclusion Criteria:

- ≥18 years of age

- Primary reason for hospitalization is skin and skin structure infection of a
complicated nature (for example, cellulitis/erysipelas, major cutaneous abscess, or
wound infection) that requires IV antibiotic treatment for an anticipated 3 to14 days
and hospitalization for management

1. Further defined as infections either involving deeper soft tissue or requiring
significant surgical intervention or infections in which the participant has a
significant underlying disease state that complicates the response to treatment

2. Are suspected or documented to be caused by MRSA

3. At least 3 of the following clinical signs and symptoms associated with the
cSSSI:

i. Pain; tenderness to palpation; ii. Elevated temperature (>37.5°Celsius [99.5°
Farenheit] oral or >38° Celsius [100.2° Farenheit] rectal); iii. Elevated white blood
count (WBC) >10,000/millimeters cubed (mm^3); iv. Swelling and/or induration;
erythema; v. Purulent or seropurulent drainage or discharge

- Physician determination that vancomycin or daptomycin would be the initial treatment
of choice for the cSSSI under study (or meets institutional criteria for use of
vancomycin or daptomycin)

- Informed consent obtained and signed

- Less than 24 hours post hospital admission

Exclusion Criteria:

- Participants with known bacteremia, osteomyelitis, septic arthritis, or endocarditis

- Conditions where surgery (in and of itself) constitutes curative treatment of the
infection (for example, amputation, incision and drainage)

- cSSSIs which can be managed with an oral antibiotic

- Participants where hospitalization is expected to be <48 hours

- Nosocomial infection

- Participants with necrotizing infections or concomitant gangrene

- Use of systemic antibacterial therapy for the infection for > 24 hours within 48 hours
prior to the start of study drug unless (a) the infecting Gram-positive pathogen was
resistant in vitro to the therapy or (b) the therapy was administered for 3 or more
days with either worsening or no improvement in the infection

- Pathogens identified at study entry to be nonsusceptible to daptomycin or vancomycin

- Participants with neutropenia or compromised immune function (that is, severe
neutropenia [absolute neutrophil count <500 cells per microliter (μL)] or is
anticipated to develop severe neutropenia during the study period due to prior or
planned therapy)

- Renal insufficiency (calculated creatinine clearance [CLcr] <30 milliliters per minute
or on dialysis)

- Known to be allergic or intolerant to daptomycin or vancomycin

- Pregnant or nursing mothers

- Suspected implanted device or prosthetic as source of infection

- Is considered unlikely to comply with study procedures or to be available for
follow-up contact