Strategies Using Off-Patent Antibiotics for Methicillin Resistant S. Aureus "STOP MRSA"

Inclusion Criteria

• Adult or child 13 years of age and older (who weighs greater than or equal to 40 kg);
• Have a skin and soft tissue infection (SSTI) with all three local findings of erythema (> 2 cm across the lesion or from a discrete wound edge), tenderness, and swelling/induration. Fever, leukocytosis, and lymphangitis will be noted, but are not enrollment criteria. SSTI with these local findings will be further categorized and defined as one of:
• Abscess - a fluctuant and/or indurated lesion, or findings of a fluid-filled cavity on soft tissue ultrasound evaluation that, when opened reveals purulent material, receiving incision and drainage (I&D) (considered standard care for abscess) and having a minimum diameter (along any axis) of at least 2 cm (measured from the borders of induration, if a fluctuant lesion, or borders of the abscess cavity on ultrasound, if not fluctuant).

Note: Although I&D of an abscess is considered standard care (i.e., patients will receive I&D whether or not they are enrolled in the study), the procedure may be performed after enrollment into the study so that prior measurements of the area of erythema and swelling/induration can be obtained unless it is an occult abscess in which the I&D will be performed prior to enrollment to verify infection type and ensure correct classification of the subject.

• Infected Wound - a wound (defined as any apparent break in the skin) with any apparent drainage limited in depth to only involving skin and subcutaneous tissue, including sutured cutaneous wounds not involving intra-abdominal surgeries contaminated with bacterial or bowel contents (e.g., colon surgery and empyema drainage), and
• Cellulitis - an area of erythema without the presence of a wound with drainage or abscess; Cellulitis associated with an abscess will be categorized as an abscess. Cellulitis associated with an infected wound will be classified as an infected wound. Patients with cellulitis and an abscess less than 2 cm will be excluded. Infected wound associated with an abscess that may require I&D, will be classified as an infected wound.
• Have the infected lesion for 7 days or less duration;
• Are to receive outpatient treatment at enrollment/baseline;
• Express willingness and ability to be contacted and return for re-evaluation according to the study protocol;
• Provide written informed consent (and for subjects ages 13-17, consent from their guardian and assent);
• Negative pregnancy test for subjects who are women of childbearing potential.

Exclusion Criteria

• Severe allergy or reaction to study drug or drugs similar to the study drug relevant to whichever study sub-trial the subject would be assigned to (e.g., patients with severe or life-threatening penicillin allergies, allergy to any cephalosporin, clindamycin, or sulfonamides, or any other drug containing sulfur such as thiazides, furosemide, and oral sulfonylureas);
• Concomitant treatment (i.e., while on study drug therapy) with coumadin, phenytoin, or methotrexate, or suspected G-6-PD or folic acid deficiency;
• Expected inability to swallow or absorb the study drug (assessed by patient history);
• Pregnancy, nursing, or expectation of becoming pregnant while on study drug;
• Perirectal (within 5 cm of anus), perineal non-skin lesions (i.e., mucosal), or paronychial location of infection. Scrotal and labial abscesses will not be excluded.
• An infection due to a mammalian bite;
• Treatment with a study drug relevant to their infection type, or another systemic antibiotic in the previous 48 hours (i.e., before screening/baseline) unless associated with treatment failure which is defined as a patient who has been on prior (non study drug) antibiotics for at least 72 hours and failed.
• Expected concurrent treatment with a topical antibiotic or another systemic antibiotic up to Test-of-Cure Visit (TOC) (note: if patient was using a topical antibiotic previously, they can still be enrolled if they agree to stop u