Effects of Antibiotic Prophylaxis on Recurrent UTI in Children

August 27, 2021 updated by: Lawson Health Research Institute

Recurrent Urinary Tract Infections in Children: Bacterial Identification, Antibiotic Susceptibility Profiling and Cytokine Levels Associated With Antibiotic Prophylaxis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients meeting the inclusion criteria will be recruited to the study at Dr. Dave's discretion through the urology clinic. As clinically indicated patients will then fall into one of two groups, patients receiving antibiotic prophylaxis or those undergoing clinical observation. This reflects the standard of care these children receive and no additional procedures are mandated.

At the initial appointment information sheets and consent forms will be given to the parent/caregiver to consider; due to the nature of the study, the parent or legal guardian will be required to give informed consent. Following the receipt of informed consent, patients will be asked to provide a mid stream urine sample given they are infection free and not currently on antibiotics. Patients will be assessed simultaneously for dysfunctional elimination syndrome (DES) through review of their 48-hour bowel bladder diary, the completed Dysfunctional Voiding Scoring System (DVSS) questionnaire and performing uroflowmetry. Patients may withdraw from the study at any stage without repercussion.

Patients in the antibiotic prophylaxis group will receive a 3-month script for antibiotic prophylaxis, if clinically indicated according to the standard of care. Septra (Trimethoprim dose 2 mg/kg) or nitrofurantoin (dose 2 mg/kg) will be the antibiotics used for prophylaxis based on past cultures or allergy history. Antibiotic prescription will be renewed at 3 months and an informal assessment on compliance will be performed through review of the number of doses left. Patients not tolerating one of these antibiotics will be offered the alternate. From months 6-12, prophylaxis will cease (washout period) unless a symptomatic UTI is suspected at which point appropriate treatment will be implemented. Lifestyle changes, behavioural modification and management of constipation will be instituted in both groups. Patients will return for follow up visits at 3, 6, 9 and 12 months. In addition, patients can return to the urology clinic at any time if UTI is suspected.

Urine samples will be collected at baseline and at 3, 6, 9 and 12 months from both groups (prophylaxis versus observation) by registered nurses at Children's Hospital, London Health Sciences Centre. Healthy patients, those with no recent history of UTI or antibiotic use or known urinary tract abnormalities, will be included to give an indication of the healthy urinary microbiota in the paediatric population. These participants will be asked to provide urine at two time points a minimum of three months apart. Samples will be assessed for bacterial identification via both culture dependent and independent methods. Antibiotic susceptibility profiles will be determined for viable organisms using the Kirby Bauer disk method and bacterial virulence analyzed via bladder and kidney cell line adherence and internalization assays, as well as PCR to determine the presence of virulence genes associated with the pathogen (adhesins, fimbriae, toxins). Urinary cytokine analysis via Luminex will also be conducted as a measure of host bladder state, immune response and disease severity.

Study Type

Interventional

Enrollment (Actual)

59

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 5W9
        • Children's Hospital - London Health Sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 15 years (CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient has experienced a minimum of 2 UTIs within the last year, as well as a culture proven UTI for inclusion into either of the RUTI groups.
  • Patients must be deemed to require antibiotic prophylaxis, at the discretion of Dr. Dave and following the standard of care, for inclusion in the antibiotic prophylaxis group.
  • Patients with no known urological abnormalities, recent history of UTI or antibiotic use are eligible for inclusion in the healthy patient group.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Antibiotic Prophylaxis
Patients with RUTI receiving Septra (Trimethoprim dose 2mg/kg) or nitrofurantoin (dose 2 mg/kg) as determined by clinician.
Drug: Antibiotic Prophylaxis
Approved clinical dosage or antibiotics
NO_INTERVENTION: Healthy Population
Healthy population
NO_INTERVENTION: Clinical Observation
Patients experiencing RUTI that do not require antibiotic prophylaxis as determined by clinician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes to the Urinary Microbiota
Time Frame: Baseline, 3-, 6-, 9-, 12-months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes to Metabolic Profiles of Urine
Time Frame: Baseline, 3-, 6-, 9- 12-months
Changes to metabolic profiles of urine as determined using gas chromatography mass spectrometry (GC-MS).
Baseline, 3-, 6-, 9- 12-months
Changes to Antibiotic Susceptibility
Time Frame: Baseline, 3-, 6-, 9-, 12-months
Changes to antibiotic susceptibility of cultured bacteria as determined by the Kirby Bauer disc diffusion method.
Baseline, 3-, 6-, 9-, 12-months
Changes in Pro-inflammatory Cytokines
Time Frame: Baseline, 3-, 6-, 9-, 12-months
Changes in pro-inflammatory cytokines associated with inflammation and immune cell recruitment will be measured using multiplexed immunoassay kits employing Luminex® xMAP fluorescent beadbased technology.
Baseline, 3-, 6-, 9-, 12-months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lawson Health Research Institute

Collaborators

University of Western Ontario, Canada

Investigators

  • Principal Investigator: Sumit Dave, MD, MCh, Assistant Professor, Pediatric Urologist, London Health Sciences Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (ACTUAL)

January 1, 2016

Study Completion (ACTUAL)

March 1, 2016

Study Registration Dates

First Submitted

February 3, 2015

First Submitted That Met QC Criteria

February 5, 2015

First Posted (ESTIMATE)

February 6, 2015

Study Record Updates

Last Update Posted (ACTUAL)

September 21, 2021

Last Update Submitted That Met QC Criteria

August 27, 2021

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R-12-387

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Urinary Tract Infection

Clinical Trials on Antibiotic Prophylaxis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United Arab Emirates

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe