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 guardianwho is able to complete the informed consent process; an assent form also will becompleted for children age 9 and older

3. Willing and able to complete the study protocol, study-related activities, andvisits

4. Diagnosis of uSSTI, either purulent cellulitis (defined as an inflammation of skinand associated skin structures) or abscess (defined as a circumscribed collection ofpus), evidenced by at least 2 of the following localized signs or symptoms on theskin for at least 24 hours:

5. Erythema

6. Swelling or induration

7. Local warmth

8. Purulent drainage

9. Tenderness to palpation or pain

10. Pus or drainage from wound that can be sent for clinical culture

11. Able to take oral antibiotic therapy, either in pill or suspension form

12. For women of childbearing potential, the participant agrees to use birth control forthe 7 days on the study medication and 7 days after completion of study medication Patients who have received prior antibacterial therapy with anti-staphylococcalactivity within the prior 14 days:

13. Received prior systemic antibacterial therapy with anti-staphylococcal activity fora skin infection and are not on it currently, and have relapse/recurrence of skininfection.

14. Received prior systemic antibacterial therapy with anti-staphylococcal activity fora skin infection (including those currently on it) without adequate source controlof their skin infection and lack of response (i.e., persistence or progression ofthe lesion) to pre-study antibacterial therapy with on-going evidence of skininfection.

15. Received prior antibiotics with anti-staphylococcal activity for non-skin infectionsand who developed a skin infection while on these antibiotics or shortly aftercompleting 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

9. Impetigo

10. Ecthyma

11. Folliculitis

12. Infections that have a high cure rate after surgical incision alone (such asisolated furunculosis) or after topical or local measures

13. Unstable psychiatric or psychological condition rendering the subject unlikely to becooperative or to complete study requirements

14. Active drug or alcohol use or dependence that, in the opinion of the siteinvestigator, would interfere with the adherence or subject compliance with studyrequirements

15. Systolic blood pressure > 180 mm Hg

16. Systolic blood pressure (SBP) less than an age-specific critical value:

17. Age 9 to 17 years: < 90 mm Hg

18. Age ≥ 18 years: < 90 mm Hg

19. Heart rate less than 45 beats per minute (BPM)

20. Heart rate greater than an age-specific-critical value:

21. Age 9 to 17 years: > 120 BPM

22. Age ≥ 18 years: > 120 BPM

23. 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)

3. Documented human or witnessed animal bite in the past 30 days at the site ofinfection

4. Received prior systemic antibacterial therapy with anti-staphylococcal activitywithin the prior 14 days who do not meet inclusion criteria 8, 9 and 10.

5. The following concomitant medications: warfarin, phenytoin, methotrexate,dofetilide, methanamine, amiodarone, leucovorin, pyrimethamine, acitretin,atovaquone, atovaquone/proguanil, isotretinoin, or sulfonylureas and systemicallyadministered antibacterial agents with activity against staphylococci

6. Diagnosed or suspected disseminated or severe S. aureus or GAS infection, includinglymphangitic spread of skin infection, septicemia, bacteremia, pneumonia,endocarditis, osteomyelitis, septic arthritis, gangrene, necrotizing fasciitis,myositis, or other serious or infections

7. Infection at an anatomical site skin requiring specialized management or specializedantimicrobial therapy, including

8. Periauricular or orbital infection

9. Perirectal infection

10. Suspected deep space infection of the hand or foot

11. Genital infection

12. Mastitis

13. Bursitis

14. 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 thediscretion of the treating physician)

15. Gastrointestinal symptoms such as nausea, vomiting, or diarrhea of a severity thatwould preclude consumption of oral antibiotics

16. Hypersensitivity or history of allergic reaction to study drug

17. History of G6PD deficiency

18. Pregnant or lactating, or intending to become pregnant within 3 months afterscreening Women of childbearing potential must have a negative urine or serumpregnancy test result within 1 day prior to initiation of study drug.

19. 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.

20. Complicated skin or soft tissue infection, such as

21. Catheter or catheter site infection within 30 days of placement

22. Surgical site infection

23. Known or suspected prosthetic device infection

24. Suspected Gram-negative or anaerobic pathogen

25. Unusual exposure history (e.g., underwater injury, fish-tank exposure, heavysoil exposure, etc)

26. History of drug-induced thrombocytopenia and documented megaloblastic anemia due tofolate deficiency.

27. Infection at the site of an area of underlying skin disease such as chronic eczema,psoriasis, atopic dermatitis, or chronic venous stasis

28. History of severe underlying immunocompromising condition or immunodeficiency, forexample

29. Chronic renal failure, creatinine clearance <30 ml/min

30. Renal dialysis within the past 180 days

31. HIV-positive with either CD4 count <200 or <4% CD4 in the past 180 days orHIV-positive and no documented CD4 count in the past 4 months

32. Cancer or malignancy with receipt of systemic chemotherapy in the prior 180days

33. Organ or bone marrow transplantation (ever), immunosuppressive therapy withinthe past 180 days, severe liver disease

34. Other serious underlying disease, as determined by the treating physician orthe investigator