Analysis of Bacterial Multidrug Tolerance in Patients Prone to Urinary Tract Infections

Systematic Analysis of Bacterial Multidrug Tolerance in Longitudinal Isolates of Patients That Are Prone to Developing Urinary Tract Infections

Prospective observational study aimed at collecting bacterial isolates from patients with recurrent or chronic UTIs, or patients with suprapubic or nephrostomy catheters.

Study Overview

• Status: Enrolling by invitation
• Conditions: Patients with Recurrent or Chronic UTIs; Patients with a Suprapubic Catheter; Patients with a Nephrostomy Catheter

Detailed Description

In some cases, antibiotic therapy is not sufficient to clear bacterial infections. The reason for this is often a reduced sensitivity of the pathogens to the administered antibiotic. This sensitivity is largely determined by genetically encoded antibiotic resistance. In addition, bacterial populations also harbor a small fraction of phenotypic variants that are temporarily insensitive to the lethal effects of antibiotics. These so-called persister cells are formed by phenotypic transition from an antibiotic-sensitive 'normal' cell to an antibiotic-tolerant dormant state. On the other hand, persister cells can also return to the 'normal' state and resume growth, giving rise to the formation of a new population. Persistors represent an important but poorly understood clinical problem. For example, they play an underappreciated role in the failure of antimicrobial therapy in chronic infections. In addition, persisters contribute to the development of antibiotic resistance.

Little is known about how persistence evolves when bacteria are confronted with continuous or repeated antibiotic pressure. In silico predictions and previous in vitro work have shown that persister levels increase with frequent antibiotic exposure and that the period in the tolerant state is determined by the duration of treatment. We hypothesize that a similar evolutionary strategy occurs in vivo and that this contributes to the chronic nature of many infections. To support this hypothesis, we propose to collect longitudinal isolates from patients with recurrent or chronic UTIs. Since these patients visit the hospital at irregular and unpredictable time intervals, we will also collect isolates from patients with a suprapubic catheter. These patients do not necessarily suffer from chronic infections, but suprapubic catheters are usually colonized by microbial biofilms. We will also collect isolates from patients with a nephrostomy catheter. Similar to patients with suprapubic catheters, these patients visit the hospital regularly (± 6 weeks interval) for routine catheter changes and during these consultations, urine samples and catheter tips are easily collected. Furthermore, many of these patients are exposed to multiple antibiotic regimens (including, in the case of nephrostomy patients, high-dose cefazolin or ceftriaxone at the time of catheter change), creating a unique opportunity to study the evolution of antibiotic tolerance in a clinical setting.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients seen at the ward or consultation

Description

Inclusion Criteria:

• Who are older than 18y
• Who are of male or female sex
• Who suffer from recurrent or chronic infections with or without neurological disorders (spina bifida, MS, paraplegic patients)
• Who have or are planned to undergo the insertion of a suprapubic catheter
• Who have or are planned to undergo the insertion of a nephrostomy catheter

Exclusion Criteria:

• Who refused the planned treatment
• Who are known to have poor therapy compliance
• Who are pregnant
• Who did not consent to participate

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collection of longitudinal bacterial strains to be used for fundamental research	Urine samples and catheter tips will be collected following SOC procedures for diagnostic purposes, at each visit of the patient. Bacteria will be isolated and further studied.	Per patient, 20 samples will be collected at 6-week intervals.

Collaborators and Investigators

• Sponsor: Natalie Verstraeten

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 4, 2024
• First Submitted That Met QC Criteria: December 4, 2024
• First Posted (Estimated): December 9, 2024

Study Record Updates

• Last Update Posted (Estimated): December 9, 2024
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Urinary Tract Infections
• Other Study ID Numbers: S65007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No