Ignite Creation Date:
2024-05-06 @ 3:43 AM
Last Modification Date:
2024-10-26 @ 11:37 AM
Study NCT ID:
NCT02357758
Status:
COMPLETED
Last Update Posted:
2021-09-21
First Post:
2015-02-03
Brief Title:
Effects of Antibiotic Prophylaxis on Recurrent UTI in Children
Sponsor:
Lawson Health Research Institute
Organization:
Lawson Health Research Institute
Study Overview
Official Title:
Recurrent Urinary Tract Infections in Children Bacterial Identification Antibiotic Susceptibility Profiling and Cytokine Levels Associated With Antibiotic Prophylaxis
Status:
COMPLETED
Status Verified Date:
2015-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
Patients meeting the inclusion criteria will be recruited to the study at Dr Daves 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 parentcaregiver 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 mgkg or nitrofurantoin dose 2 mgkg 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 Childrens 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
At the initial appointment information sheets and consent forms will be given to the parentcaregiver 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 mgkg or nitrofurantoin dose 2 mgkg 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 Childrens 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None