Effects of Antibiotic Prophylaxis on Recurrent UTI in Children

NCT02357758 | Completed Phase 4 Results

• 1 other identifier: R-12-387
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Approximately, 3% of males and 8% of females will develop a urinary tract infection (UTI) during childhood, and most of these will be effectively treated by short-term antibiotic therapy. A subset of these children (20-48%), will develop recurrent UTI (RUTI), which may have long-term effects in the form of hypertension or renal damage. In an effort to prevent RUTIs physicians prescribe sulfamethoxazole-trimethoprim (Septra) or nitrofurantoin as low dose antibiotic prophylaxis. However, recent evidence suggests that during prophylactic therapy the body is exposed to antibiotic levels capable of increasing antibiotic resistance and bacterial virulence. This has been shown to be true in the uropathogens E. coli and Staphylococcus saprophyticus, yet it is not known if Enterococcus sp. demonstrate similar mechanisms. Additionally, antibiotics have been shown to disrupt the natural balance of the human microbiome, potentially leading to major long term problems. As a uropathogen, enterococci consistently rank in the top 3 causes of RUTI, especially in children under 3 years of age. Additionally, Enterococcus is notorious for developing antibiotic resistance and studies have shown that children with enterococcal UTIs exhibit a higher rate of recurrence than those with non-enterococcal UTIs. The investigators hypothesize the current practice of antibiotic prophylaxis in children with RUTI is detrimental and can change the bacterial and sensitivity profiles of these patients.

Conditions

Urinary Tract Infection; Recurrent Urinary Tract Infection

Keywords

Antibiotic Prophylaxis; Urinary Microbiota

Outcome Measures

Primary Outcomes (1)

• Changes to the Urinary Microbiota

  Changes to the urinary microbiota were measured as changes in the colony forming units (CFUs) of Enterococcus sp., Escherichia coli, Klebsiella sp./Enterobacter sp., Staphylococcus saprophyticus, or Pseudomonas sp./Staphylococcus aureus when the participant urine was cultured on CHROMagar Orientation. The data was analyzed in terms of bacterial counts, presence/absence, and presence at or above the diagnostic threshold for UTI (10\^5 CFU/mL of one species). Here we present participant midstream urine samples that met the diagnostic threshold for UTI at baseline.

  Baseline, 3-, 6-, 9-, 12-months

Secondary Outcomes (3)

• Changes to Metabolic Profiles of Urine

  Baseline, 3-, 6-, 9- 12-months

• Changes to Antibiotic Susceptibility

  Baseline, 3-, 6-, 9-, 12-months

• Changes in Pro-inflammatory Cytokines

  Baseline, 3-, 6-, 9-, 12-months

Study Arms (3)

Antibiotic Prophylaxis

ACTIVE COMPARATOR

Patients with RUTI receiving Septra (Trimethoprim dose 2mg/kg) or nitrofurantoin (dose 2 mg/kg) as determined by clinician.

Drug: Antibiotic Prophylaxis

Healthy Population

NO INTERVENTION

Healthy population

Clinical Observation

NO INTERVENTION

Patients experiencing RUTI that do not require antibiotic prophylaxis as determined by clinician.

Interventions

Antibiotic Prophylaxis DRUG

Approved clinical dosage or antibiotics

Antibiotic Prophylaxis

Eligibility Criteria

• Age: 3 Years - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may not qualify if:

• Patients with an abnormal urinary tract as determined through the use of ultrasound and, given an abnormal ultrasound, or greater than two febrile UTIs, a voiding cystourethrogram (VCUG). The use of both ultrasound and VCUG given these indications is standard of care.

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• University of Western Ontario, Canada: collaborator

Study Sites (1)

Children's Hospital - London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Related Publications (1)

• Whiteside SA, Dave S, Seney SL, Wang P, Reid G, Burton JP. Enterococcus faecalis persistence in pediatric patients treated with antibiotic prophylaxis for recurrent urinary tract infections. Future Microbiol. 2018 Aug;13:1095-1115. doi: 10.2217/fmb-2018-0048. Epub 2018 Aug 22.

  PMID: 30132694 DERIVED

MeSH Terms

Conditions

Urinary Tract Infections

Interventions

Antibiotic Prophylaxis

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chemoprevention; Drug Therapy; Therapeutics; Premedication

Results Point of Contact

• Title: Dr. Sumit Dave
• Organization: London Health Sciences Centre

Sumit.Dave@lhsc.on.ca

519.685.8439

Study Officials

• Sumit Dave, MD, MCh

  Assistant Professor, Pediatric Urologist, London Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2015
• First Posted: February 6, 2015
• Study Start: September 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: March 1, 2016
• Last Updated: September 21, 2021
• Results First Posted: October 14, 2019

Record last verified: 2015-09

Locations

CA (1)