# Bacteriophage to treat multidrug‐resistant UTI in Persons with Spinal Cord Injury

> **NIH VA I01** · MICHAEL E DEBAKEY VA MEDICAL CENTER · 2022 · —

## Abstract

Our overall purpose is to take aim at two urgent clinical problems for persons with spinal cord injury (SCI). The
first problem is ongoing morbidity from urinary tract infections (UTI) and mortality from bacteremia and sepsis
arising from pathogens in the urinary tract. Urinary tract infections and associated complications are a common
threat to the wellbeing and even survival of persons with spinal cord injury (SCI). The second clinical dilemma
is the disproportionate harm persons with SCI are experiencing from multidrug -resistant bacteria, particularly
Escherichia coli, the most common urinary pathogen. We plan to develop bacteriophage, viruses that kill specific
strains of bacteria, as a treatment for multidrug-resistant E. coli UTI and sepsis in SCI. Phage have numerous
properties that suggest they will be effective in this role, including lack of cross resistance with antibiotics, ability
to attack biofilms, evolvability in vitro, and being a self-renewing agent at the site of infection. Phage therapy for
resistant urinary organisms has potential applications in the SCI population beyond UTI treatment and also for
the Veteran population in general, such as for bladder sterilization prior to urologic procedures. Phage therapy
aligns with VHA antibiotic stewardship efforts and may alleviate the burden of Clostridium difficile experienced
by Veterans. The work we propose here with the most common urinary pathogen in SCI, E. coli, would
subsequently be applied to the other SCI urinary pathogens to create broadly effective phage cocktails. Project
Objectives: We will develop E. coli-specific phages that are efficacious against a broad range of SCI-specific E.
coli isolates from our VA hospital in a mouse model of catheter-associated urinary tract infection (CAUTI) and/or
sepsis. Aim 1 is to determine the efficacy of phage in killing antibiotic-resistant E. coli in murine infection models
of CAUTI (1A), bacteremia (1B), and in combination with antibiotics to which the infecting E. coli pathogen is
resistant (1C). Aim 2 is to develop and test a bank of phages effective against contemporary E. coli isolates
from Veterans with SCI. In Aim 2A, we will actively collect E. coli clinical isolates from Veterans with SCI, creating
an SCI-specific bacterial strain bank. In Aim 2B, we will collect and experimentally generate phages with broad
host range against E. coli, creating a bank of sequenced phage that cover over 80% of the SCI E. coli strains. In
Aim 2C we will create phage cocktails from our phage bank, and test the efficacy of the cocktails in the mouse
model of CAUTI induced by SCI E. coli. Aim 3 is to examine the emergence of phage-resistant E. coli during
treatment of CAUTI and determine how to overcome phage resistance. Aim 3A: Determine if E. coli persistence
after phage treatment results from bacterial resistance to phage. Aim 3Bb: Determine if a “recharge” dose of
phage several days into therapy prevents recurrence of E. coli. Methods: We p...

## Key facts

- **NIH application ID:** 10350575
- **Project number:** 5I01RX002595-04
- **Recipient organization:** MICHAEL E DEBAKEY VA MEDICAL CENTER
- **Principal Investigator:** BARBARA Wells TRAUTNER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10350575

## Citation

> US National Institutes of Health, RePORTER application 10350575, Bacteriophage to treat multidrug‐resistant UTI in Persons with Spinal Cord Injury (5I01RX002595-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10350575. Licensed CC0.

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