Background and objectives: Febrile urinary tract infection (fUTI) in well-appearing children is conventionally treated with a standard 10-day course of oral antibiotic. The objective of this study is to determine the noninferiority (5% threshold) of a 5-day amoxicillin-clavulanate course compared with a 10-day regimen to treat fUTIs. Methods: This is a multicenter, investigator-initiated, parallel-group, randomized, controlled trial. We randomly assigned children aged 3 months to 5 years with a noncomplicated fUTI to receive amoxicillin-clavulanate 50 + 7.12 mg/kg/day orally in 3 divided doses for 5 or 10 days. The primary end point was the recurrence of a urinary tract infection within 30 days after the completion of therapy. Secondary end points were the difference in prevalence of clinical recovery, adverse drug-related events, and resistance to amoxicillin-clavulanic acid and/or to other antibiotics when a recurrent infection occurred. Results: From May 2020 through September 2022, 175 children were assessed for eligibility and 142 underwent randomization. The recurrence rate within 30 days of the end of therapy was 2.8% (2/72) in the short group and 14.3% (10/70) in the standard group. The difference between the 2 groups was -11.51% (95% confidence interval, -20.54 to -2.47). The recurrence rate of fUTI within 30 days from the end of therapy was 1.4% (1/72) in the short group and 5.7% (4/70) in the standard group (95% confidence interval, -10.4 to 1.75). Conclusions: This study demonstrates that a 5-day course is noninferior to a 10-day course of oral amoxicillin-clavulanate.
