Comparing Optimal Step-down Therapy for Children with Invasive MRSA Trimethoprim-Sulfamethoxazole vs. Clindamycin for the Treatment of Children with Invasive MRSA Infections
James Wood, MD
Primary Investigator
Brief description of study
What is the purpose of this study?
This is a comparative effectiveness study of two antibiotics typically prescribed in the clinical setting of pediatric patients with osteoarticular infections (OAI, including acute osteomyelitis and septic arthritis) and head and neck infections (HNIs) caused by methicillin resistant Staphylococcus aureus (MRSA).. The goal of this study is to determine whether treatment with trimethoprim-sulfamethoxazole (TMP-SMX) results in: 1) better treatment outcomes compared to clindamycin and 2) is associated with maintaining greater nasal and gut biodiversity in pediatric patients with OAI, (including acute osteomyelitis and septic arthritis) and HNIs caused by methicillin resistant Staphylococcus aureus (MRSA).
Detailed description of study
What will happen during the study?
This is a 3-year (2.5-years of enrollment), prospective, two-arm, open-label, single center, randomized comparative study to compare oral step-down antibiotic treatment with TMP-SMX versus clindamycin for pediatric patients ages 2 months to 18 years of age, with OAIs and HNIs due to MRSA. The study will randomize approximately 125 patients (~62 in each arm). Participants will be stratified by infection type (OAI and HNI), and MRSA infection status (confirmed vs. suspected) and randomized 1:1 to receive either TMP-SMX or clindamycin.
- Randomization/assignment to the treatment arm will occur while the participant is inpatient.
- Collection of biome samples: Participants who agree to provide biome samples will self-collect samples at two timepoints.
- Pre-treatment samples will be self-collected while inpatient, but before oral step-down treatment begins.
- Post-treatment samples be self-collected in patient's home or other location of the participant's choosing.
- The End of Treatment (EOT) visit will occur in the privacy of the participant's clinic room or will occur remotely (i.e. phone, virtual) as preferred by the participant.
- Weekly symptom checks will occur according to the availability of options and participant preference. 1) Remotely: a member of the study team will speak to the parent by phone and/or virtual options. The study team will ask the questions and record the parent's responses. 2) Paper: the parent will complete the symptom checker on paper and return the original to the study team either in-person at the EOT, or will return to the study team with provided postage-paid envelope. 3) Electronically: participants will be emailed a unique link or QR code to a REDCap database to complete the symptom checker online.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: OAI, osteomyelitis, septic arthritis), HNI. facial/orbital cellulitis, cervical lymphadenitis, mastoiditis, deep neck abscess, Riley
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Age: 60 days - 80 years
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Gender: All
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 radiographic confirmation of OAI
o Focal finding- pain/swelling over a bone/joint, or restricted movement/failure to bear weight
o Systemic finding- fever >38oC, or elevated CRP or elevated ESR or elevated WBC or elevated WBC in synovial fluid
OR
o 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
o Focal finding- facial pain or redness, eye pain or proptosis, neck or throat pain or swelling, ear pain or proptosis
o Systemic finding- fever >38oC, or elevated CRP or elevated ESR or elevated WBC
OR
o 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
o 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)
o Suspected MRSA- treatment for MRSA by the clinical team without microbiologic confirmation (e.g., negative cultures)
3) Currently ready or planned to be transitioned to oral antibiotic therapy by the clinical team
4) 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 as part 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 affected bone/joint
4) Infection (OAI or HNI) resulting from penetrating wounds, open fractures, major trauma, foreign body or post-operative infection.
5) Spinal osteomyelitis
6) Underlying chronic renal, gastrointestinal, liver, or heart disease that would be expected 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 preclude participation 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
