Short Therapy for Febrile UTI in Childhood

Study Overview
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Brief Summary
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Febrile urinary tract infections (UTIs) are common in children, but there is no consensus concerning the duration of the antibiotic treatment. Current recommendations include the use of an oral antibiotic, chosen between amoxicillin and clavulanic acid or a third-generation cephalosporin (ceftibuten), for a minimum of seven to a maximum of 14 days. In an antibiotic overuse-sparing model, proper evaluation of a shorter therapy in the treatment of febrile UTI in childhood is lacking. The objective of this randomized controlled trial is to assess the non inferiority of a five days oral course of amoxicillin and clavulanic acid vs the standard 10-day regimen in the treatment of febrile UTIs in children. The trial results might provide evidence of the non-inferiority of a short duration of the antibiotic course for the treatment of febrile UTI in childhood, contributing to a reduction in the over-use of antibiotics and consequently limiting the emergence of antibiotic resistance.

Official Title
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Shortened Antibiotic Therapy for Febrile Urinary Tract Infection (UTI) in Childhood: a Multicenter Randomized Controlled Trial

Conditions
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Urinary Tract Infections

Intervention / Treatment
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* Drug: Amoxicillin and Clavulanic Acid in Oral Dose Form


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 3 months to 5 years; Clinical diagnosis of febrile UTI, defined by fever ≥38°C and positive result of urinalysis (nitrite and/or leukocyte esterase positivity) in two consecutive urine samples collected by bladder catheterization or clean catch (19). The diagnosis of UTI will be then confirmed by positive urine culture for a single type of bacterium with a charge> 105 CFU /ml as per the Recommendations of the Italian Society of Pediatric Nephrology (SINePe) (19). Exclusion Criteria: Complicated febrile UTI (septic appearance, repeated vomiting impeding oral administration of the antibiotic, severe-moderate dehydration with the need for intravenous antibiotic therapy) Presence of an inserted urinary catheter Immunodeficiency Hypersensitivity to the active substance or other beta-lactam antibiotics Any antibiotic treatment received in the previous 15 days. Presence of another poorly controlled chronic medical condition (diabetes, inflammatory bowel disease, etc.) Presence of neurological bladder Presence of phenylketonuria or glucose-galactose malabsorption Intestinal malabsorption Poor compliance History of jaundice or liver failure positive

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 5 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Short treatment group<br>Amoxicillin and clavulanic acid 50 mg/kg three times daily administered orally for 5 consecutive days | Drug: Amoxicillin and Clavulanic Acid in Oral Dose Form<br>* 50 mg/kg three times daily administered orally<br>|
| Active Comparator: Standard treatment group<br>amoxicillin and clavulanic acid 50 mg/kg three times daily administered orally for 10 consecutive days | Drug: Amoxicillin and Clavulanic Acid in Oral Dose Form<br>* 50 mg/kg three times daily administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of infection recurrence | Infection recurrence rate is defined as the reappearance of signs and symptoms of febrile UTI by the first day after the end of antibiotic therapy | within 30 days after the end of the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete resolution of signs and symptoms | The complete resolution of the signs and symptoms (clinical assessment and urinalysis) related to the infection evaluated at the end of the treatment, without the need for additional or alternative antibiotic therapy (short term clinical efficacy) | within 30 days after the end of the intervention | 
| Rate of antibiotic-resistant or of opportunistic strains in relapses | Antibiotic resistance is defined as the presence of positive urinalysis and positive urine culture for a single type of bacterium resistant to amoxicillin and clavulanic acid, after treatment in case of relapse. The bacterial growth will be considered significant if >105 colony-forming unit/ml (CFU/ml) (>104 CFU/ml for urine samples collected by bladder catheterization). Urine cultures containing more than one bacterial species will be considered contaminated. | within 30 days after the end of the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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short antibiotic therapy, urinary tract infection, children