The proposed study is a prospective, open-label, randomized, multi-center trial of ceftaroline versus vancomycin for the treatment of ABSSSI in patients documented or at risk for MRSA. Patients admitted to the Detroit Medical Center, Henry Ford Hospital, or St. John Medical Center in Detroit Michigan with a documented ABSSSI between April 2012 and November 2015 will be evaluated for inclusion. Patients must present with at least 3 of the following local signs/symptoms: pain, tenderness, swelling erythema, warmth, drainage/discharge, induration, and lymph node swelling/tenderness. Patients will be randomized 1:1 ceftaroline or vancomycin with optional anaerobic and/or Gram-negative coverage. The assignment of study drug will follow a randomized list that was previously generated via a computerized random mix block generator (nQuery Advisor® 7.0) and available at each of the study sites. Patients will be randomized to ceftaroline intravenously at 600 mg infused over 1 hour every 12 hours for patients with normal renal function. Patients randomized to vancomycin will receive the standard 15 mg/kg dose based on total body weight infused over 1 hour q 12 hour, dose and interval adjusted based on creatinine clearance and via institution-specific pharmacy protocol to target serum trough concentrations of 10-20 mg/L within the first 72 hours. Outcomes measured in the Clinically Evaluable patient population include day two or three size reduction (percentage) and clinical response at end of therapy or discharge.

Inclusion Criteria:

• Acute bacterial skin and skin structure infection (cellulitis, major abscess, surgical site infection)
• Presence of MRSA or documented risk factors for MRSA (prior antibiotic use 60 days, prior hospital exposure 180 days, skin ulcers, central venous catheter)
• Anticipating no less than two days of hospital admission
• Signed informed consent

Exclusion Criteria:

• Gas gangrene/progressive necrotizing infections
• Osteomyelitis
• Infections due to Gram-negative pathogens or other Gram-positive pathogens if S. aureus or Streptococcus is not present
• Pathogens known at the study entry to be resistant to ceftaroline or vancomycin
• Anticipated to require non-study antibiotic active against S. aureus for another reason
• Treatment for the current episode of ABSSSI for > 24 hours with another intravenous anti-MRSA antibiotic
• Surgical (I & D) as definitive/curative treatment
• Presence of prosthetic hardware or invasive devices suspected to be the source of infection but cannot be removed
• Life expectancy < 2 months
• Open burn wound > 30% total body surface area
• Pregnant or nursing mothers
• Known allergic reaction to vancomycin or ceftaroline