Individualized Antibiotic Therapy in Children With Acute Uncomplicated Febrile Urinary Tract Infection

Study Overview
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Brief Summary
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An investigator-initiated, open-label, multi-center, randomized, non-inferiority trial of children aged 3 months to 13 years with acute uncomplicated febrile urinary tract infection. The primary objective is to determine whether individualized antibiotic therapy based on an algorithm (experimental arm) versus standard antibiotic therapy of 10 days (control arm) can reduce the number of days with antibiotic therapy within 28 days after treatment initiation without increasing the risk of recurrent urinary tract infection regardless of the pathogen or death of any cause within 28 days after end of treatment. Children will be randomized 1:1. The medical treatments received are identical in both groups.

Official Title
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Individualized Antibiotic Therapy Versus Standard Care in Children With Febrile Urinary Tract Infection

Conditions
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Febrile Urinary Tract Infection

Intervention / Treatment
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* Other: Individualized antibiotic therapy
* Other: Standard antibiotic therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical suspicion of febrile (≥38 °C) urinary tract infection. Positive urine culture of uropathogenic bacteria obtained by either suprapubic bladder aspiration, sterile intermittent catheterization, or midstream urine. Suprapubic bladder aspiration: any growth of bacteria. Sterile intermittent catheterization: monoculture with ≥10^3 cfu/ml. Midstream urine x 2: Monoculture with the bacteria in both tests with ≥10^4 cfu/ml. Midstream urine x 2: Monoculture with the bacteria in both tests with ≥10^5 cfu/ml in one test and 10^3 cfu/ml in another test. Midstream urine x 1 (≥10 years of age): Monoculture with ≥10^5 cfu/ml. 3 months to 13 years of age (corrected age in case of premature birth). Parents fluent in Danish or English. Informed consent both parents. All children who do not receive any empirical antibiotic therapy but have a positive urine culture (approximately 48 hours after urine sample collection) can be included if fever (≥ 38.0 °C) is present and the child is initiated with relevant antibiotic therapy. ¨ Children can be included regardless of whether intravenous or oral antibiotics were given as empirical therapy. Exclusion Criteria: Non-Danish civil registration number. Not resident in the Capital Region or Region Zealand in Denmark at primary visit. Previous inclusion in the trial. History of febrile (≥38 °C) urinary tract infection in the last 28 days before the primary visit. Antibiotic treatment in the last two weeks before the primary visit. Three or more episodes with febrile (≥38 °C) urinary tract infection within one year of the primary visit (including the current episode). Previous complicated episode of febrile (≥38 °C) urinary tract infection (e.g., renal abscess or urosepticemia) Non-compliance ≥3 doses of antibiotics during empirical therapy. Elevated creatinine. Prophylactic antibiotic treatment. Known urogenital abnormalities (i.e., obstructing uropathies; vesicoureteral reflux; multicystic dysplasia; renal dysplasia; renal hypoplasia; renal agenesis; duplex kidney; polycystic kidney disease; neurogenic bladder dysfunction; hypospadias). Septic. Positive blood culture (if contamination is not suspected). Immune deficiency. Systemic immunosuppressive therapy.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individual group<br>In the individual group, the participants receive individualized antibiotic therapy. | Other: Individualized antibiotic therapy<br>* Individualized antibiotic therapy is based on the duration of illness after treatment initiation, as the antibiotic therapy can be stopped three days after the participant has become healthy. The participant is classified as healthy if he/she is afebrile (<38.0 °C), has experienced significant clinical improvement, and have no flank pains or dysuria.<br>|
| Active Comparator: Standard group<br>In the standard group, the participants receive standard antibiotic therapy as defined by the national guideline. | Other: Standard antibiotic therapy<br>* Standard antibiotic therapy is 10 days of antibiotic therapy regardless of the duration of illness after treatment initiation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with recurrent urinary tract infection regardless of the pathogen or death of any cause |  | within 28 days after end of treatment | 
| Number of days with antibiotic therapy |  | within 28 days after treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days with absence from school or daycare due to illness |  | within 28 days after randomization | 
| Proportion of participants with recurrent urinary tract infection regardless of the pathogen or death of any cause |  | within 100 days after end of treatment |