Short and Long Term Outcomes of Doxycycline Versus Trimethoprim-Sulfamethoxazole for Skin and Soft Tissue Infections Treatment

Inclusion Criteria: 1. Age 9 years to 85 years 2. Able to complete the informed consent process or, if a minor, a parent or guardian who is able to complete the informed consent process; an assent form also will be completed for children age 9 and older 3. Willing and able to complete the study protocol, study-related activities, and visits 4. Diagnosis of uSSTI, either purulent cellulitis (defined as an inflammation of skin and associated skin structures) or abscess (defined as a circumscribed collection of pus), evidenced by at least 2 of the following localized signs or symptoms on the skin for at least 24 hours: 1. Erythema 2. Swelling or induration 3. Local warmth 4. Purulent drainage 5. Tenderness to palpation or pain 5. Pus or drainage from wound that can be sent for clinical culture 6. Able to take oral antibiotic therapy, either in pill or suspension form 7. For women of childbearing potential, the participant agrees to use birth control for the 7 days on the study medication and 7 days after completion of study medication Patients who have received prior antibacterial therapy with anti-staphylococcal activity within the prior 14 days: 8. Received prior systemic antibacterial therapy with anti-staphylococcal activity for a skin infection and are not on it currently, and have relapse/recurrence of skin infection. 9. Received prior systemic antibacterial therapy with anti-staphylococcal activity for a skin infection (including those currently on it) without adequate source control of their skin infection and lack of response (i.e., persistence or progression of the lesion) to pre-study antibacterial therapy with on-going evidence of skin infection. 10. Received prior antibiotics with anti-staphylococcal activity for non-skin infections and who developed a skin infection while on these antibiotics or shortly after completing these antibiotics. Exclusion Criteria: 1. Cellulitis without abscess, drainage, or other culturable exudate. 2. Hospital inpatient 3. Hospitalization within the prior 14 days 4. Residence in a long-term skilled nursing facility 5. Requirement for hospitalization for skin infection or other condition 6. Previous enrollment in this protocol 7. Participation in another clinical trial within the previous 30 days 8. Superficial skin infection only, including 1. Impetigo 2. Ecthyma 3. Folliculitis 4. Infections that have a high cure rate after surgical incision alone (such as isolated furunculosis) or after topical or local measures 9. Unstable psychiatric or psychological condition rendering the subject unlikely to be cooperative or to complete study requirements 10. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with the adherence or subject compliance with study requirements 11. Systolic blood pressure \> 180 mm Hg 12. Systolic blood pressure (SBP) less than an age-specific critical value: 1. Age 9 to 17 years: \< 90 mm Hg 2. Age ≥ 18 years: \< 90 mm Hg 13. Heart rate less than 45 beats per minute (BPM) 14. Heart rate greater than an age-specific-critical value: 1. Age 9 to 17 years: \> 120 BPM 2. Age ≥ 18 years: \> 120 BPM 15. Oral temperature (or equivalent rectal, tympanic membrane, axillary defined in Table 2) less than 35.5° C (95.9° F) 16. Oral temperature (or equivalent rectal, tympanic membrane, axillary defined in Table 2) greater than age-specific critical value: 1. Age 9 to 17 years: \> 38.5° C (101.3° F) 2. Age ≥ 18 years: \> 38.5° C (101.3° F) 17. Documented human or witnessed animal bite in the past 30 days at the site of infection 18. Received prior systemic antibacterial therapy with anti-staphylococcal activity within the prior 14 days who do not meet inclusion criteria 8, 9 and 10. 19. The following concomitant medications: warfarin, phenytoin, methotrexate, dofetilide, methanamine, amiodarone, leucovorin, pyrimethamine, acitretin, atovaquone, atovaquone/proguanil, isotretinoin, or sulfonylureas and systemically administered antibacterial agents with activity against staphylococci 20. Diagnosed or suspected disseminated or severe S. aureus or GAS infection, including lymphangitic spread of skin infection, septicemia, bacteremia, pneumonia, endocarditis, osteomyelitis, septic arthritis, gangrene, necrotizing fasciitis, myositis, or other serious or infections 21. Infection at an anatomical site skin requiring specialized management or specialized antimicrobial therapy, including 1. Periauricular or orbital infection 2. Perirectal infection 3. Suspected deep space infection of the hand or foot 4. Genital infection 5. Mastitis 6. Bursitis 22. Radiographic evidence or suspicion of gas in the tissue or foreign body infection (note: radiography is not required for screening and can be performed at the discretion of the treating physician) 23. Gastrointestinal symptoms such as nausea, vomiting, or diarrhea of a severity that would preclude consumption of oral antibiotics 24. Hypersensitivity or history of allergic reaction to study drug 25. History of G6PD deficiency 26. Pregnant or lactating, or intending to become pregnant within 3 months after screening Women of childbearing potential must have a negative urine or serum pregnancy test result within 1 day prior to initiation of study drug. 27. Severe or morbid obesity with a body mass index (BMI) \>45 kg/m2; patients above BMI \>45 can be enrolled if their weight is \< 100 kg kg/m2. 28. Complicated skin or soft tissue infection, such as 1. Catheter or catheter site infection within 30 days of placement 2. Surgical site infection 3. Known or suspected prosthetic device infection 4. Suspected Gram-negative or anaerobic pathogen 5. Unusual exposure history (e.g., underwater injury, fish-tank exposure, heavy soil exposure, etc) 29. History of drug-induced thrombocytopenia and documented megaloblastic anemia due to folate deficiency. 30. Infection at the site of an area of underlying skin disease such as chronic eczema, psoriasis, atopic dermatitis, or chronic venous stasis 31. History of severe underlying immunocompromising condition or immunodeficiency, for example 1. Chronic renal failure, creatinine clearance \<30 ml/min 2. Renal dialysis within the past 180 days 3. HIV-positive with either CD4 count \<200 or \<4% CD4 in the past 180 days or HIV-positive and no documented CD4 count in the past 4 months 4. Cancer or malignancy with receipt of systemic chemotherapy in the prior 180 days 5. Organ or bone marrow transplantation (ever), immunosuppressive therapy within the past 180 days, severe liver disease 6. Other serious underlying disease, as determined by the treating physician or the investigator