Abstract

Trimethoprim-sulfamethoxazole (TMP-SMX) is active against most Staphylococcus aureus isolates but is not widely used for treatment of pediatric osteoarticular infections. This was a comparative effectiveness study of hospitalized patients ≤18 years treated with TMP-SMX versus other antibiotic regimens for acute osteoarticular infections between 2016 and 2021 at three hospitals using inverse probability of treatment weighted propensity score analysis. The primary outcome was treatment failure, a composite of unanticipated emergency department (ED) or outpatient visits, hospital readmissions, extension or change of antibiotic therapy due to inadequate clinical response, or death, all within 6 months after completing antibiotics. The secondary outcome was antibiotic-associated adverse events (AEs) within 6 months. The exposed group for the treatment failure analysis included children who received ≥7 days of TMP-SMX and did not experience treatment failure while on another antibiotic. Children receiving at least one dose of TMP-SMX were the exposed group for the AE analysis. 116 patients met eligibility criteria; 26 (22.4%) patients were classified into the TMP-SMX cohort and 90 (77.6%) into the other antibiotics cohort (most commonly clindamycin, vancomycin, and cefazolin). There was no significant difference in treatment failure between TMP-SMX and other antibiotics (43% vs 19%; 95% CI 0.9-10.4). More patients in the TMP-SMX cohort experienced an unplanned ED or outpatient visit (OR 4.8, 95% CI 1.3-17.8). There was no difference in hospital readmission, antibiotic change, or duration extension. Exposure to TMP-SMX was associated with more AEs (41% vs 19%, p=0.012). Treatment with TMP-SMX was not associated with greater clinical failure but was associated with more AEs compared to alternative agents for the treatment of pediatric acute osteoarticular infections.

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