Efficacy and safety of individualised versus standard 10-day antibiotic treatment in children with febrile urinary tract infection (INDI-UTI): a pragmatic, open-label, multicentre, randomised, controlled, non-inferiority trial in Denmark.

BACKGROUND

The optimal antibiotic duration for febrile urinary tract infection (UTI) in children remains uncertain. We aimed to assess whether individualised treatment was non-inferior to standard 10-day treatment in terms of recurrent UTI and superior in reducing overall antibiotic exposure.

METHODS

INDI-UTI was a pragmatic, open-label, multicentre, randomised, controlled, non-inferiority trial conducted at eight Danish hospitals. Children aged 3 months to 12 years who were febrile (≥38°C), within 24 h of treatment start, and with significant growth of uropathogenic bacteria were randomly assigned (1:1) using a web-based module with randomly permuted blocks to individualised or standard 10-day treatment. Main exclusion criteria included known urinary tract abnormalities, complicated medical history, bacteraemia, and elevated serum creatinine. The individualised group stopped treatment 3 days after adequate clinical improvement (ie, absence of fever, flank pain, and dysuria), with a minimum treatment duration of 4 days. The primary outcomes were recurrent UTI within 28 days after treatment cessation (non-inferiority margin 7·5 percentage points) and total antibiotic days within 28 days of treatment initiation (superiority assessment). No sample size calculation was performed for the assessment of total antibiotic days. Safety was assessed in all included patients. Main analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT05301023.

FINDINGS

Between March 28, 2022, and March 3, 2024, 694 patients were assessed for eligibility and 408 patients were randomly assigned to individualised (n=205; median antibiotic duration 5·3 days [IQR 4·8 to 6·5]) or standard 10-day treatment (n=203; 10·0 days [10·0 to 10·0]). Median age was 1·5 years (IQR 0·7 to 5·4), and there were 326 (80%) female and 82 (20%) male participants. Recurrent UTI within 28 days occurred in 23 (11%) of 205 patients in the individualised group and 12 (6%) of 203 patients in the standard 10-day group (difference 5·3 percentage points, one-sided 97·5% CI -∞ to 11·1, p=0·24). Total antibiotic days within 28 days were 6·0 (IQR 5·3 to 7·5) in the individualised group and 10·0 (10·0 to 10·0) in the standard 10-day group (median difference -4·0 days [97·5% CI -4·5 to -3·7], p<0·0001). The incidence rate of antibiotic-related adverse events within 28 days was 6·8 per 100 patient-days in the individualised group and 11·1 per 100 patient-days in the standard 10-day group (rate ratio 0·61 [95% CI 0·47 to 0·80], p=0·0003). Serious adverse events occurred in 17 (8%) of 205 patients in the individualised group and 15 (7%) of 203 patients in the standard 10-day group (difference 0·9 percentage points [95% CI -4·6 to 6·5], p=0·79).

INTERPRETATION

Children with febrile UTI assigned to individualised treatment duration had an increased risk of recurrent UTI (by 5·3 percentage points) but reduced antibiotic use and fewer adverse event days within 28 days compared with those assigned to standard 10-day treatment. These findings highlight the potential of individualised treatment strategies to reduce antibiotic exposure and associated harms in most children with febrile UTI, supporting antimicrobial stewardship goals. Further research is needed to identify those requiring 10-day treatment to avoid compromising care for most children with febrile UTI who respond well to shorter durations.

FUNDING

Copenhagen University Hospital Rigshospitalet Research Fund, Innovation Fund Denmark, and Greater Copenhagen Health Science Partners.