Symposium Research: Redefining How Urinary Tract Infections Are Diagnosed and Treated.

This article was written by Ana Valeria Aguirre Guemez, MD, and Abigail Fox, BA, MedStar Health Research Institute Clinical Research Assistant and incoming Georgetown University School of Medicine Medical Student Class of 2029.

Two related, award-winning studies presented at the MedStar Health – Georgetown University Research & Education Symposium could redefine how UTIs are diagnosed in patients with neurogenic lower urinary tract dysfunction.

The pain of a urinary tract infection (UTI) is common, especially among people with neurogenic lower urinary tract dysfunction (NLUTD), abnormal bladder function due to a neurologic condition. 

The limitations of current methods to diagnose and treat UTIs mean patients sometimes wait days to be prescribed the right antibiotic. Our two related studies investigate a new way to handle UTIs that could provide definitive answers in minutes instead of days. This new method aligns with our new understanding of the urobiome, meaning we look at all the good and bad bacteria in the bladder instead of one strain growing in a lab.  

NLUTD, sometimes called neurogenic bladder, can be caused by an injury or disease of the nervous system, such as spinal cord injury, dementia, stroke, or Parkinson’s disease. People with NLUTD can have difficulty emptying their bladder completely or at all, and other challenges that can lead to a bacterial infection in the urinary tract. 

Studies have shown that people with NLUTD have an average of 2.5 UTIs per year, much higher than the general population average of not even one per year. About 20% of people with NLUTD have UTIs that keep coming back and negatively impact their quality of life. 

We can do better for patients. That’s why our research aimed to identify a new method to help providers get better information about UTIs sooner.

A faster way to check for bacteria in urine.

To diagnose a UTI, doctors today use three main criteria:

• Assessment of urinary symptoms: Such as a burning sensation, frequent or sudden need to urinate, cloudy urine, and others

• Urinalysis (UA): This test, which is used to check for bladder inflammation, can take up to 24 hours to return results

• Standard urine culture (SUC): A laboratory can take 3 days to determine whether bacteria are growing in a urine sample. Results from these cultures aren’t precise, missing many of the bacteria present in the bladder.

We tested a new way. Bacteria in the bladder break down compounds , such as carbohydrates and amino acids, to get energy. Then they release a compound called nicotinamide adenine dinucleotide + hydrogen, or NADH, during their metabolic process. When we isolate the bacteria in the urine and expose them to a blue dye called resazurin, the NADH released by the bacteria causes the blue dye to glow fluorescent pink, a process called reduction. 

Using a device that automatically separates the bacteria from the urine and contains an instrument known as a spectrofluorometer, we can measure how much reduction occurs as the bacteria grow. By comparing this measurement to the patient’s urine without bacteria, we can derive the urine resazurin reduction ratio (uRRR), which could tell us how much the bacteria are metabolizing and could indicate a UTI. The results are available in about 50 minutes. 

Our research set out to find out if this method could accurately indicate whether a patient has an infection, and which antibiotics can help.

Dr. Ana Valeria Aguirre Guemez (left) and Abigail Fox, BA (right).

Comparing UTI diagnosis methods.

We designed a cross-sectional study to explore the relationship between uRRR and symptoms, bladder inflammation, bacterial growth, and a combination of all three factors. Our study was the first time this method was tried in human urine. 

Almost 300 adults with NLUTD participated in this study. Researchers collected urine samples from patients who manage their urine in different ways:

• Voiding their bladder on their own

• Using a temporary tube to empty the bladder, known as an intermittent catheter

• Using an indwelling catheter, which remains in the bladder to drain urine into a collection pouch

To understand their clinical symptoms of UTI, we used a standard questionnaire. We analyzed their urine using urinalysis, SUC, and our new uRRR method. This showed that uRRR identified the presence of bacteria more quickly than traditional methods:

• uRRR results were higher among people with UTI symptoms

• uRRR results were higher in patients who had more signs of inflammation in their urine

• uRRR was higher in patients whose urine showed bacteria growth in SUC

• uRRR results were higher in patients who had a combination of all three: UTI symptoms, urine inflammation, and bacteria growth in SUC

Redefining treatment by testing antibiotic effectiveness.

Our related cross-sectional study examined how well uRRR can help us understand which antibiotics will treat a urinary tract infection. The difference with standard methods is that uRRR tests the entire community of bacteria (called the urobiome), while SUC isolates individual types. 

Using samples from the same group of patients, we compared the uRRR results to SUC and found:

• uRRR was sensitive: it correctly identified the presence of bacteria in 89% of samples

• uRRR was specific: it could tell when there was very little bacteria in 97% of samples

Overall, uRRR accurately identified bacterial growth in 93.5% of samples.

To help improve how UTI is treated, we tested how the uRRR results changed when samples were exposed to five common antibiotics: Ceftriaxone, Levofloxacin, Cephalexin, Ciprofloxacin, and Bactrim.

In most cases, uRRR could determine which antibiotics worked as well as the SUC, but much faster. The results only differed in a small number of samples. When uRRR and SUC disagreed, we found (81% of the time) it was because the samples contained more than one type of bacteria. This mix of bacteria can change how well antibiotics work. 

These results indicate that uRRR can accurately detect metabolic activity of the bacteria and tell clinicians which medications can help relieve urinary tract infection symptoms, so patients receive effective treatment sooner. 

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

A first step toward improving UTI care.

These exciting results could point the way toward revolutionizing how UTIs are diagnosed and treated. First, we have more work to do. Our studies were cross-sectional, meaning they looked at data from a specific time. This can help us see the relationship between factors, but it can’t say for sure that one thing causes another. 

We’re getting ready to begin a prospective observational study that will enable us to monitor a group of patients over time and measure their specific outcomes. This study and others like it allow MedStar Health Research Institute to work to close gaps in care for people with NLUTD. This is important, new work that can help patients get answers sooner and suffer less from the disruptive symptoms of UTIs.