Trimethoprim-sulfamethoxazole vs. Clindamycin for the Treatment of Children With Invasive MRSA Infections

Inclusion Criteria:

1. 60 days to 18 years of age (inclusive) at the time of oral step down treatment

2. Diagnosed by the clinical team with OAI or HNI:

• OAI- at least 1 focal finding and 1 systemic finding OR radiographicconfirmation of OAI

• Focal finding- pain/swelling over a bone/joint, or restrictedmovement/failure to bear weight

• Systemic finding- fever >38oC, or elevated c-reactive protein (CRP) orelevated erythrocyte sedimentation rate. (ESR) or elevated white bloodcell count (WBC) or elevated WBC in synovial fluid OR

• Radiographic confirmation- findings consistent with osteomyelitis orseptic arthritis - Plain radiograph, MRI, CT or ultrasound, bone scanresult indicating abnormal bone, subperiosteal or bone marrow findingsconsistent with infection

• HNI- at least 1 focal finding and 1 systemic finding OR radiographicconfirmation of HNI

• Focal finding- facial pain or redness, eye pain or proptosis, neck orthroat pain or swelling, ear pain or proptosis

• Systemic finding- fever >38oC, or elevated CRP or elevated ESR or elevatedWBC OR

• Radiographic confirmation- findings consistent with facial/orbitalcellulitis, cervical lymphadenitis, mastoiditis, or deep neckinfection/abscess (including peritonsillar, retro- and para-pharyngeal.Plain radiograph, MRI, CT or ultrasound, bone scan result indicatingabnormal findings consistent with infection

3. Treated by the clinical team for confirmed MRSA or suspected MRSA infection

• Confirmed MRSA- positive culture for MRSA from a sterile body fluid (e.g.,blood, abscess, bone, synovial fluid, or other surgical specimen)

• Suspected MRSA- treatment for MRSA by the clinical team without microbiologicconfirmation (e.g., negative cultures)

4. Currently ready or planned to be transitioned to oral antibiotic therapy by theclinical team

5. OAI or HNI symptoms < 14 days at the time of hospital admission

Exclusion Criteria:

1. Enrollment in another interventional study or receipt of investigational drug aspart of a research trial within the past 30 days.

2. Known cancer, acquired or primary (including sickle cell anemia or G6PD deficiency)immunodeficiency

3. Underlying bone disease, presence of hardware /implantable device in affectedbone/joint

4. Infection (OAI or HNI) resulting from penetrating wounds, open fractures, majortrauma, foreign body or post-operative infection.

5. Spinal osteomyelitis

6. Underlying chronic renal, gastrointestinal, liver, or heart disease that would beexpected to potentially affect absorption or the metabolism of assigned drug

7. Inability to take medicine by mouth, gastrostomy, jejunostomy or nasogastric tube

8. Received intravenous antibiotic therapy as the treatment for OAI or HNI >14 days.

9. Inability or unwilling to consent

10. Any social or medical conditions judged by the study clinician to precludeparticipation because it could negatively affect the participant.

11. Allergy to both TMP-SMX and clindamycin

12. Known MRSA isolate resistant to both TMP-SMX and clindamycin

13. Patient is known to be pregnant at the time of enrollment