Research Explores New Treatment for Recurrent UTI After Spinal Cord Injury.

Department of Defense-funded research now underway could help solve the problem of recurrent urinary tract infections in people with spinal cord injuries.

Urinary tract infection (UTI) is among the most common health complications for people with spinal cord injuries, and it can keep coming back after treatment. We’re studying a new treatment for recurrent UTI in patients with neurogenic bladder that could improve outcomes—with fewer side effects and less antimicrobial resistance.

Neurogenic lower urinary tract dysfunction (NLUTD), or neurogenic bladder, is a condition in which bladder function is compromised due to an injury or disease of the nerves, brain, or spinal cord. It can happen because of stroke, multiple sclerosis, Alzheimer’s, or Parkinson’s disease. It is most common among patients with spinal cord injuries; Research shows 70%-84% of these patients will have NLUTD at some point.

Symptoms can vary depending on the location of a patient’s nervous system damage. Usually, the bladder’s muscles and sphincter work together to control the release of urine. NLUTD can result in bladder dysfunction, such as:
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• Overactive NLUTD: Nerves send signals to the bladder too often, causing spasms or a feeling that the bladder is full when it isn’t which can lead to sudden urges to urinate and leaking. Frequent spasms can cause the bladder wall to thicken, reduce the bladder’s ability to store urine and increase the risk of infection.
• Underactive NLUTD: Muscles contract weakly or not at all, meaning the bladder doesn’t empty completely. Retained urine can cause infections or other serious health problems. 
• Both overactive and underactive NLUTD: These conditions can occur simultaneously in people with neurogenic bladder, resulting in leaking and retention. 
• Detrusor sphincter dyssynergia: The bladder muscles and sphincter sometimes work against each other. When an overactive bladder squeezes against a sphincter that’s closed shut, urine stays in the bladder despite the urge to urinate. The condition can be dangerous because it can cause urine to back up into the kidneys.

• Catheter use to help drain urine can introduce bacteria to the bladder
• Compromised ability to fight infection (due to immune system dysfunction, which is common in patients with NLUTD and makes fighting infection more difficult)
• Reduced clearance of bacteria from the bladder due to retaining urine too long or emptying incompletely
• Transfer of bacteria from stool—many patients with neurogenic bladder also have neurogenic bowel, a condition with a similar cause that can lead to abnormal bowel function such as constipation or incontinence.
• Greater ability of bacteria to adhere to the bladder lining

My colleagues and I are in the early days of a new study funded by the U.S. Department of Defense’s Congressionally Directed Medical Research Programs - Spinal Cord Injury Research Program. We’re exploring a new treatment using both an antibiotic medication (gentamicin) and a live biotherapeutic product (Lactobacillus rhamnosus, sometimes called a “probiotic”) to resolve UTI in patients with NLUTD and keep it from coming back.
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Combining antibiotic and probiotic treatment.

Gentamicin is a medication used to treat various bacterial infections in the body. Traditionally, it is given as an injection into a vein or muscle.

To prevent UTI in patients with NLUTD, doctors have the additional option to give antibiotics like gentamicin directly into the bladder through a catheter. By administering gentamicin with this technique, called intravesical therapy, we’re reducing the patient’s systemic exposure to the antibiotic. 

We have several studies currently underway at the MedStar National Rehabilitation Hospital through our Rehabilitation Research and Training Center, Spinal Cord Injury Model System (both funded by NIDILRR) and other studies to learn more about the role of the live biotherapeutic, Lactobacillus, and the bladder.

In our current research, we’re combining intravesical antibiotic therapy with an experimental approach to using the Lactobacillus live biotherapeutic product. We’re examining this method to learn if we hope can help restore the bladder’s microbiome to stop UTI from coming back. To my knowledge, this is the first time an antibiotic and a live biotherapeutic agent have been used in combination.

One of the goals of this new treatment method is the introduction of Lactobacillus to help regrow a healthy urobiome (bacterial ecosystem) in the bladder after an antibiotic has been given. Typically, UTI treatment involves only a course of antibiotics like gentamicin, with the goal of eradicating bacteria. But, in so doing, we’re not considering how the urobiome reconstitutes after the course of antibiotics is complete. 

This is a new approach to the problem of UTI among people with NLUTD, and our research will answer important questions, such as:

• Can the two agents be given to a patient at the same time, or will gentamicin kill the Lactobacillus inside the bladder and as such, do they need to be given separately?
• If they need to be given separately, how long should we wait to ensure gentamicin is no longer in the bladder?
• What is the effect of giving Lactobacillus with or after an intravesical antibiotic like gentamicin on the bladder urobiome?

My colleague, Alan J. Wolfe, PhD, at Loyola University Chicago will use bladder organoid models (tissue cultures that mimic the structure and function of the bladder) in his lab so we can begin to answer these questions. Next, we’ll explore the best dosing strategies in animal models by testing the approach in mice with my colleague Catherine Forster, MD. This will pave the way for testing this promising treatment in human patients. 
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Related reading: Study Demonstrates Costs of Antibiotic-Resistant UTIs and the Power of Partnership.

Innovating to help patients.

While intravesical therapy isn’t new, the problem of antimicrobial resistance is huge. Antimicrobial resistance—when microbes mutate to resist drugs— makes infections harder to treat and increases the risk of severe illness and death as a result. The U.S. Centers for Disease Control and Prevention estimates 2.8 million antimicrobial-resistant infections each year, an “urgent global public health threat” that kills 1.27 million people across the globe annually. 

Overuse of antibiotics is a major contributor to antimicrobial resistance worldwide. In our treatment, intravesical therapy delivers gentamicin directly to the bladder so the rest of the patient’s body isn’t exposed.

We’ve been working on this treatment for more than a decade because we believe it can be a major advancement in how we treat UTI, for patients with NLUTD and perhaps others, too. But it is still experimental. 

Intravesical treatment of recurring UTI with gentamicin and Lactobacillus could allow us to provide treatment that is much more targeted, with fewer side effects, that can stop UTI from coming back while making a positive impact on antimicrobial resistance worldwide.

If proven safe and effective, this research could rapidly become available to MedStar Health patients and others to end suffering associated with UTI that keeps coming back.