Rebecca G Same

Background Trimethoprim–sulfamethoxazole (TMP–SMX) is active against most Staphylococcus aureus isolates but is not widely used for the treatment of pediatric osteoarticular infections. Methods This was a comparative effectiveness study of hospitalized patients ≤18 years treated with TMP–SMX vs. other antibiotic regimens for acute osteoarticular infections between 2016 and 2021 at 3 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 1 dose of TMP–SMX were the exposed group for the AE analysis. Results One-hundred and sixteen 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 .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 = .012). Conclusions 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.