Noninferiority of Short Course Antibiotics for Febrile UTI: the STOP Trial.

1. In this randomized trial 5 days of antibiotics for febrile urinary tract infection was noninferior to standard 10 day treatment.

2. Recurrence rate of infection at 30 day follow up was lower in the short course group.

Evidence rating: 1 (Excellent)

Study Rundown: Febrile urinary tract infection (UTI) is a common occurrence in outpatient pediatrics. After 3 months of age, the traditional treatment in otherwise healthy, well appearing children, has been a 10 day course of oral antibiotics. However, lack of clear data has made this recommendation debatable. The STOP trial was designed to determine whether a 5-day course of amoxicillin-clavulanic acid is not inferior to a traditional 10-day course in regards to infection recurrence and antibiotic resistance.

This multi-center, parallel-group, randomized, control trial was conducted over 2 years in numerous pediatric emergency rooms in Italy. The authors were able to recruit and randomize 142 eligible subjects. Subjects were randomized to three times daily amoxicillin-clavulanic acid for 5 days or 10 days. The primary endpoint was UTI recurrence within 30 days. Secondary endpoints were clinical recovery with treatment, adverse events related to therapy, and antibiotic resistance assessed through antibiogram. All subjects were reevaluated at 5 and 30 days or when clinically indicated. All subjects underwent renal and bladder ultrasound.

There were no statistically significant differences between the groups. In regards to primary endpoint, the rate of UTI recurrence in those receiving 5-days of therapy was 2.8 %, while the rate of recurrence in the 10-day group was 14.3 %. Similarly, the short course group had similar or better rates of symptom resolution, need for further treatment, and adverse events. The most common adverse event was diarrhea. There were no significant differences on renal or bladder ultrasound present between the two groups. The development of antibiotic resistance was not demonstrated.

This well designed study demonstrates noninferiority of 5-days of antibiotic therapy compared with standard 10 day therapy for febrile UTIs in otherwise healthy children. In other studies, similar findings have been shown for children with community acquired-pneumonia. This is the first such study to demonstrate this in regards to UTI. Interestingly, this study also demonstrated similar findings for children with recurrent UTI.

This study suggests that 5-days of antibiotic therapy is noninferior to traditional 10 day treatment and does not lead to increased risk of recurrence or the development of antibiotic resistance. Though the study was unblinded, the strengths of being a randomized, prospective, multi-center study suggest that this is reliable data and that current treatment guidelines could be reconsidered. As the note, further trials are required.

Click to read the study in Pediatrics.

Relevant Reading: Are We Ready for Short Antibiotic Courses for Febrile Urinary Tract Infections in Young Children?

In-Depth [randomized controlled trial]: The Short-course oral antibiotic Therapy of acute Pyelonephritis in children (the STOP trial) was a noninferiority, multicenter, parallel-group, randomized, controlled trial conducted in Italy in 8 pediatric emergency rooms from May 2020 through September 2022. The study recruited children 3 months to 5 years of age with an uncomplicated, febrile UTI. Febrile UTI was defined as clinically significant fever above 38 C with positive urine dup. Patients with complications such as indwelling catheters, immunodeficiency, or other complicated medical issues were excluded. Of 175 considered to participate, 142 were ultimately randomized and included in the analysis with 72 patients in the 5-day arm and 70 patients in the 10-day arm. The mean age at recruitment was 14 months for both groups and the population was well balanced in gender distribution.

Both interim and final analyses concluded that the recurrence rate in the 5-day group was lower at 2.8% (2/72 subjects) than in the standard 10-day group at 14.3% (10/70). The difference between the groups was 11.51% (95% CI, -20.52 to -2.47). This confidence interval fell below the determined threshold of +5%, thus confirming noninferiority of 5-day treatment.

Image: PD

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