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

Inclusion criteria

• 60 days to 18 years of age (inclusive) at the time of oral step down treatment
• Diagnosed by the clinical team with OAI or HNI:

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

• Focal finding- pain/swelling over a bone/joint, or restricted movement/failure to bear weight
• Systemic finding- fever >38oC, or elevated c-reactive protein (CRP) or elevated erythrocyte sedimentation rate. (ESR) or elevated white blood cell count (WBC) or elevated WBC in synovial fluid OR
• Radiographic confirmation- findings consistent with osteomyelitis or septic arthritis - Plain radiograph, MRI, CT or ultrasound, bone scan result indicating abnormal bone, subperiosteal or bone marrow findings consistent with infection
• HNI- at least 1 focal finding and 1 systemic finding OR radiographic confirmation of HNI

• Focal finding- facial pain or redness, eye pain or proptosis, neck or throat pain or swelling, ear pain or proptosis
• Systemic finding- fever >38oC, or elevated CRP or elevated ESR or elevated WBC OR
• Radiographic confirmation- findings consistent with facial/orbital cellulitis, cervical lymphadenitis, mastoiditis, or deep neck infection/abscess (including peritonsillar, retro- and para-pharyngeal. Plain radiograph, MRI, CT or ultrasound, bone scan result indicating abnormal findings consistent with infection
• 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 microbiologic confirmation (e.g., negative cultures)
• Currently ready or planned to be transitioned to oral antibiotic therapy by the clinical team
• OAI or HNI symptoms < 14 days at the time of hospital admission

Exclusion criteria

• Enrollment in another interventional study or receipt of investigational drug as part of a research trial within the past 30 days.
• Known cancer, acquired or primary (including sickle cell anemia or G6PD deficiency) immunodeficiency
• Underlying bone disease, presence of hardware /implantable device in affected bone/joint
• Infection (OAI or HNI) resulting from penetrating wounds, open fractures, major trauma, foreign body or post-operative infection.
• Spinal osteomyelitis
• Underlying chronic renal, gastrointestinal, liver, or heart disease that would be expected to potentially affect absorption or the metabolism of assigned drug
• Inability to take medicine by mouth, gastrostomy, jejunostomy or nasogastric tube
• Received intravenous antibiotic therapy as the treatment for OAI or HNI >14 days.
• Inability or unwilling to consent
• Any social or medical conditions judged by the study clinician to preclude participation because it could negatively affect the participant.
• Allergy to both TMP-SMX and clindamycin
• Known MRSA isolate resistant to both TMP-SMX and clindamycin
• Patient is known to be pregnant at the time of enrollment