Five days of oral antibiotic treatment for febrile urinary tract infections (UTIs) in kids was noninferior to the standard 10-day course, the randomized controlled STOP trial showed.

The recurrence rate of all UTIs — febrile and non-febrile — within 30 days of treatment with oral amoxicillin-clavulanate acid was 2.8% in the short-term group compared with 14.3% in the long-term group, for a difference of -11.51% (95% CI -20.52 to -2.47), reported Antimo Tessitore, MD, of the University of Trieste in Italy, and colleagues in Pediatrics.

“This difference in favor of the short group was unexpected,” they wrote. “Because the use of the O’Brien-Fleming criteria, with the increase of the CI from 95% to 99.5%, confirmed the noninferiority results, the Steering Committee decided that the results were robust and agreed to stop the trial, in light of a low recruitment rate and to allow us to highlight the short therapy’s effectiveness promptly.”

When looking solely at febrile UTIs post-treatment, the 30-day recurrence rate was 1.4% in the short-term group versus 5.7% in the long-term group, for a difference of -4.33% (95% CI -10.40 to 1.75), they noted. Again, noninferiority held at a CI of 99.5%.

“We hypothesized that a shorter duration of antibiotic therapy should not compromise treatment effectiveness and the recurrence rate of UTI, possibly reducing antimicrobial resistance,” Tessitore and colleagues wrote. “If confirmed as effective, the shorter course should minimize adverse effects, reduce healthcare costs, and improve adherence.”

“This would change the traditional axiom from ‘complete the cycle to prevent resistance’ to ‘prevent resistance, take what is needed,'” they added.

Notably, results of the STOP trial differed from those recently reported from the SCOUT trial, which showed that stopping antibiotics when children’s UTI symptoms improved after an initial 5-day course yielded a 4.1% rate of persistent symptomatic UTI by follow-up at days 11-14 compared with 0.6% when kids had the full 10-day course.

The upper limit of the confidence interval for the absolute difference exceeded the prespecified 5% margin required for noninferiority, the SCOUT researchers noted in JAMA Pediatrics. However, they added that the failure rate of short-course therapy was still low enough to suggest it could be considered as a reasonable option for kids exhibiting clinical improvement after 5 days of treatment.

“STOP and SCOUT have similarities but differ in multiple ways that were likely cumulatively important toward generating divergent results,” Charles Woods, MD, MS, and James Atherton, MD, PhD, both of the University of Tennessee Health Science Center College of Medicine and Children’s Hospital at Erlanger in Chattanooga, wrote in an accompanying commentary. “It is difficult to disentangle factors in either study that identify subgroups for whom shorter courses would be appropriate or longer courses necessary.”

Given the greater sample size and “slightly more rigorous study design” of the SCOUT trial, Woods and Atherton noted that they tended to concur with the commentary on the SCOUT trial:

• Currently available direct and indirect (adult) data support treating UTI in children that appears limited to cystitis with courses no longer than 5 days
• When there is clinical concern for pyelonephritis, it seems prudent, until there are more data, to maintain a modest preference for courses on the order of 10 days

“Meanwhile, collectively we should not STOP SCOUT-ing out the likely nuanced answers to questions regarding the optimal duration of antibiotics for young children with febrile UTI,” Woods and Atherton wrote.

The STOP trial was conducted at eight pediatric emergency departments in Italy from May 2020 through September 2022, with 72 patients (mean age 14.1 months, 34.7% boys) randomized to receive amoxicillin-clavulanic acid in three doses for 5 consecutive days and 70 patients (mean age 14.2 months, 32.9% boys) randomized to receive the treatment for 10 days.

At baseline, there were similar demographic and clinical characteristics between groups. The prevalent microorganism was Escherichia coli.

Resolution of symptoms occurred in 97.2% of cases in the short-term group and 92.9% of cases in the long-term group, Tessitore and colleagues reported. The need for further antibiotic treatment was 1.4% and 5.7%, respectively.

In post-hoc analyses excluding patients with known vesicoureteral reflex or patients with non-E. coli UTIs, both confirmed the noninferiority of short-term therapy.

Limitations to the study included that the randomization of treatment duration was unblinded.

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