This is a prospective, randomized clinical trial comparing daptomycin to vancomycin in the Emergency Department (ED) treatment of complicated skin and skin structure infection in the Rapid Diagnosis and Treatment Center (RDTC). In brief, a convenience sample of patients who are admitted to the RDTC cellulitis protocol in the ED will be randomized to either vancomycin, which is currently an accepted care standard in the RDTC cellulitis protocol, or daptomycin, which is the experimental treatment in this study. The primary hypothesis is that daptomycin treatment is as efficacious as standard therapy in the treatment of ED cellulitis.

Specific Aim 1: Compare the efficacy of daptomycin to the efficacy of vancomycin for the treatment of complicated skin and skin structure infection in the ED. Patients eligible for the RDTC Cellulitis Treatment Protocol will be screened for inclusion in the study. After informed consent, patients will be randomized to receive either daptomycin or vancomycin (1:1 ratio). A case report form (CRF) detailing medical history, clinical characteristics, and treatments will be completed. The patients will be evaluated for meeting RDTC discharge criteria. The following time points will be collected: 1. actual time patient meets discharge criteria based on the RDTC cellulitis protocol; 2. time of disposition defined as the time treating physician writes discharge orders; and, 3. time the patient actually leaves the emergency department. Subsequently, the patient will be followed up by telephone to ascertain whether a change in antibiotic therapy or a return ED visit for complicated skin and skin structure infection occurred within 30 days of the initial RDTC enrollment Specific Aim 2: Compare the change in area and erythema of the cellulitic lesion between patients treated with daptomycin and patients treated with vancomycin. Patients enrolled in the study will have serial digital photographs of their primary lesion taken. The images will be processed blinded to clinical data and asynchronous to the ED stay. The change in lesion area and erythema will be calculated.

Inclusion Criteria:

• Admitted to RDTC to the Cellulitis Protocol
• 18 yrs old or greater
• Able and willing to give informed consent
• Hemodynamically stable (systolic blood pressure >90mmHg and heart rate <120 beats per minute)

Exclusion Criteria:

• Antibiotics given prior to enrollment
• Suspected necrotizing infection
• Diabetic foot ulcer
• Genitourinary involvement
• Post operative infection (not including simple wound closure infection)
• Suspected gouty or septic arthritis
• Chronic Lymphangitis
• Requiring routine hemodialysis
• Patient reported allergy to Vancomycin
• Patient reported allergy to Daptomycin
• Participation in another investigational treatment study within 30 days prior to enrollment
• Prisoner
• Pregnant or breast-feeding
• Complicated skin and skin structure infection of the face

161 patients were screened;104 were initially enrolled. 3 patients were withdrawn prior to randomization; 1 patient was transferred to OR, 1 patient was admitted prior to randomization, 1 patient was prescribed a different antibiotic;1 patient was withdrawn not meet inclusion criteria. 39 patients in each treatment group completed follow-up.