Seeking new treatment for UTIs
BY TRACEY O’SHAUGHNESSY
REPUBLICAN-AMERICAN
For most women, a urinary tract infection — painful as it may be — is a nuisance.
The typical treatment for UTI, which can cause a burning sensation and urge to urinate, is a series of antibiotics that can often lead to adverse side effects, such as yeast infections.
But for some women, UTIs are persistent, painful and difficult to treat. In part, that’s because such patients develop a resistance to the plethora of antibiotics taken to fight the disease.
Women’s Health Research at Yale recently granted Dr.
Toby C. Chai a research award to determine whether the application of localized estrogen can use the body’s own resources to prevent and treat chronic urinary tract infections.
“We don’t know a lot about how to prevent or how to treat UTIs,” said Chai, a professor and vice chair of research in urology. “We’re running out of antibiotics.
We utilize them so frequently the bacteria have become smart. They develop resistance quickly. We really have to open up new avenues to be able to find new treatments for infection.”
An estimated one in two women will get a UTI at some point in their lives. But a postmenopausal woman who receives treatment for an UTI has a 25 percent chance of developing recurrent UTIs. Often, says Dr.
Nahida Khan of Griffin Hospital in Derby, UTIs are misdiagnosed. In elderly women in particular, hormonal changes cause atrophy in the urethra, a thinning of the lining of the cells. That condition can manifest with burning symptoms, similar to that of a UTI.
A urinary tract infection causes a burning urgency that some women describe as feeling like they have glass in their bladder. Men get UTIs as well, but women are more prone to them because their urethra is shorter. UTIs are 10 times more common among women than men.
Also, after menopause, the lining of the bladder becomes thinner and therefore less able to fight against the bacteria that cause infection.
The New York Times reports that after the flu and common cold, urinary tract infections are the most common medical complaint among women in their reproductive years.
“An elderly woman can become very sick much quicker from a UTI,” said Dr. Kathleen Burlison, who specializes in internal medicine with Franklin Medical Group, an affiliate of Saint Mary’s Hospital in Waterbury. “As we get older, we tend to develop other diseases like diabetes, heart disease, which can make UTIs more difficult to treat. Somebody who is in their 70s, they become weaker, they don’t eat as well.”
If left untreated, the bacteria within the bladder can travel up into the kidneys and cause serious and potentially life-threatening kidney infections, or spread into the bloodstream (sepsis) and then elsewhere in the body.
“The question people have is: Will I die from the infection?” Chai said. “The answer is a UTI usually does not go far unless you have other conditions. The fear is you will get blood poisoning, or sepsis. But the incidence of sepsis is low unless you have other problems. They just get very terrible quality of life.
They are going to the bathroom frequently, they get burning pain, bladder pain, feeling like there’s bits of glass inside the bladder.”
But antibiotics, the standard treatment, present their own problems. “What happens when they’re in their fourth infection in 12 months?” Chai asked. “It’s more antibiotics. And you hope they don’t develop a superbug. Doctors are picking the only option they have.”
CHAI SAID RESEARCHERS ARE particularly concerned about these recurrences of UTIs. His group wants to use mice to see whether doctors can treat recurrent UTIs by applying estrogen directly to the bladder, and avoid antibiotics, which have grown less effective through overuse.
But Chai is aware that estrogen is a thorny issue for women because it has been known to play a role in the development of breast cancer, heart attack and stroke.
“No one wants to use estrogen. They’ll be squeamish about breast cancer, they’ll be concerned about stroke.”
Chai said that he knows estrogen has a positive effect on the bladder lining. But he wants to look deeper at what other mechanisms are turned on through this estrogen to determine if those might be as useful or more useful in treating UTIs.
“I’m trying to see what if the body’s natural defense mechanisms can be utilized to fight infection,” Chai said.
“And the natural defense I’m looking at is the female hormone estrogen on the bladder lining. I first validate that estrogen in the animal model does protect against UTI.
(Then) I want to see what other signals are turned on by this estrogen so that I can leverage these secondary mechanisms that are turned on by estrogens that hopefully will not give the side effects of breast cancer, blood clots, which are allied to estrogen.”
IT’S NOT JUST HORMONES
that make women more susceptible to UTIs as they age, Kahn said. “As you get older, your immune system is weakened. That leads to a more colonization of bacteria. Your body’s ability to fight the bacteria goes down.”
Additionally, she said, the pH, or acidic level, of a woman’s urinary tract decreases over time. As the urinary tract becomes less acidic, the bacteria are more able to cling to normal tissue in your urinary tract, she said.
“Normally it’s an acidic environment that kills bacteria,” Kahn said. “As you get older, the pH becomes basic.
When the bacteria becomes basic, the bacteria are able to cling to the normal tissue in your tract.”
Moreover, bladder muscles become weaker, leading to more urinary retention, a risk factor for UTIs. The infection can also cause delirium in certain patients, particularly among those with dementia. That’s why Kahn suggests a urinalysis when an elderly patient’s condition changes dramatically.
“Sometimes we will see an elderly person who is confused and we have no other explanation so we seek a urinalysis,” Burlison said.
Dr. Toby C. Chai of Women’s Health Research at Yale University in New Haven is researching whether applying localized estrogen can spark the body to cure urinary tract infections.
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