The search for a vaccine for urinary tract infections

If you are alive and in possession of a vagina, chances are you will get a urinary tract infection at some point in your life. UTIs are one of the most common bacterial infections, so you might assume that modern medicine has nearly perfected its treatment options for this uncomfortable and potentially dangerous condition.

Unfortunately you would be wrong.

“If you have a common urinary tract infection, you tend to get a lower quality antibiotic,” Paul Garofolo, co-founder and CEO of pharmaceutical company Locus Biosciences, told The Daily Beast. “And these days, 50 percent of the time, you’re back in the doctor’s office in 30 to 90 days and saying, ‘Hey, I’ve got another one.’ And you’re angry.”

The data shows that as many as one in four people who contract a UTI will have a recurrent infection, defined as more than one UTI in a six-month period, or more than three in a year. Not only are these acutely painful, they can be frustrating and frightening to deal with over and over again. A study of 29 women with recurrent urinary tract infections found that patients were concerned about “creating a sample of a UTI infection that will be resistant to anything” and other drug-resistant infections in the future. Others complained that taking antibiotics for a UTI is “like killing a mosquito with a grenade,” but doctors didn’t want to look at other treatments.

A number of factors that we are still investigating play a role in how susceptible a person is to recurrent urinary tract infections, including the composition of the microorganisms in the genitourinary tract, hormone levels, antibiotic resistance and the body’s own immune system.

What is known, however, is that a course of antibiotics routinely prescribed today for a urinary tract infection is a ticking time bomb. “The fact that UTIs are very common, along with the fact that we don’t always test in a lab to determine which antibiotics are most appropriate, means it’s a good recipe for creating resistance,” said Lisa Bebell, infectious diseases doctor at Massachusetts General Hospital, The Daily Beast told. Broad-spectrum antibiotics used as second- and third-line defenses can have a ripple effect on the body’s microbiome and even lead to increased susceptibility to UTIs in the future by setting the stage for a vaginal yeast infection.

It’s not surprising that scientists and patients want a better alternative. More modern UTI research these days, of the kind that Locus Biosciences is pursuing, is taking unusual and experimental approaches to see what treatments could clear the infection without causing more damage to the body (and we’re talking therapies that cure infection definitively). or avoid – not cranberry juice).

James Cook / Massachusetts General Hospital

Crucially, this new research builds on a counterintuitive and bold proposition: What if we treated a bacterial infection with something other than antibiotics?

“The goal is certainly to eventually take antibiotics out of the treatment paradigm for these infections,” Garofolo said.

A post-antibiotic world

A fundamental question that could lead to better treatments is why certain people are more likely to have a UTI that just won’t go away. Age plays a significant role, as UTI rates are higher in young, sexually active women and postmenopausal women than in other groups. A confluence of research is beginning to show that hormones and microbial communities may play a bigger role than previously thought. A paper, published Friday by Texas researchers in the journal Cell reports medicineresolves some of the obscurity surrounding these relationships, starting with the misconception that the breeding grounds for UTI-causing bacteria — the urinary tract and bladder — are sterile.

“Decades of medical dogma have adopted the sterility of urine and the urinary tract; however, a robust body of work has demonstrated the existence of a human genitourinary microbiome,” the authors wrote in the study. The microbiome consists of all living microorganisms that reside in the human body, and disturbances in their balance can predispose to certain diseases.

The Texas researchers studied the microbiomes and urine of 75 postmenopausal women with varying histories of UTIs, to find out whether recurrent UTIs correlated with irregular microbiomes and to identify causes for the imbalance. They found that the genitourinary microbiomes of women with a history of recurrent UTIs had higher levels of bacterial groups commonly found during active infection, compared to women without a history of UTIs. On the other hand, women without a recurrent UTI history had higher estrogen levels associated with more Lactobacillus species – probiotic bacterial strains that can protect against infection.

The fact that UTIs are very common, along with the fact that we don’t always test in a lab to determine which antibiotics are most appropriate, makes it a good recipe for creating resistance.

Lisa Bebell, Massachusetts General Hospital

Topical or vaginal estrogen cream for people who have gone through menopause may be helpful in breaking the cycle of recurrent UTIs, said Bebell, who was not involved in the study. She added that “the jury is still out” and definitive proof of the benefit of estrogen is needed.

At least one other study is looking at whether another hormone, testosterone, may help prevent UTIs. In a small pilot study published in May, researchers in New York found that a testosterone vaginal cream reduced the abundance of Lactobacillus species and improved general vaginal health. Larger sample sizes and longer follow-up will be needed to determine whether the hormone can prevent UTIs, the authors wrote.

Others are pushing for a more permanent solution to UTIs: a vaccine that can be offered annually or semi-annually. While some vaccines are already available to prevent UTIs in countries outside the US, Soman Abraham, a pathology researcher at Duke University School of Medicine, told The Daily Beast that these existing methods have not shown a high degree of efficacy. “We believe that one of the reasons those current immune vaccines aren’t as protective is the antibody levels.” [they produce] are not high enough,” he said.

However, Abraham and his team think they may have found a better version — one that has been shown to reduce harmful bacteria in the bladders of mice threefold. The body responds to bacteria in the urinary tract by shedding cells in the walls of the bladder and shedding other immune cells until this process is complete; the vaccine, on the other hand, cancels those signals and gives the fighters the green light to take care of the bacteria before they can multiply. Abraham and his team are working to demonstrate the safety of their vaccine in other animals so they can eventually test it on humans.

Race for the cure

While estrogen, probiotics, and vaccines can be effective measures to prevent UTIs, there remains the issue of treating a UTI once it’s contracted. For this, researchers have at least one surprising solution in the pipeline: phage therapy.

There’s another reason why using antibiotics to treat UTIs is like putting a square peg in a round hole, said Greg German, a medical microbiologist at the University of Toronto. Bacteria in the genitourinary tract form biofilms, which are like a “wall of defense” that antibiotics can only partially penetrate. Bacteria behind the biofilm remain unharmed and can reinfect a person once they have finished a course of medication.

“After my medical training I had the opportunity to treat patients with resistant infections and I was very frustrated because all patients had to use intensive IV therapy,” German told The Daily Beast. “I wanted to see if there was anything else to do; phage therapy was a natural opportunity.”

I always tell people that Hugh Hefner died from this. A urinary tract infection can be quite scary.

Paul Garofolo, Locus Biosciences

Bacteriophages are naturally occurring viruses that have evolved to be highly contagious to very specific strains or types of bacteria. Unlike a broad-spectrum antibiotic that kills good and bad microorganisms with little discrimination, a cocktail of phages can instead wipe out the most common cause of UTIs, Escherichia coli, and have no other impact on the rest of the microbiome. German is recruiting for a single-person clinical trial that will test the effectiveness of a phage cocktail in treating a drug-resistant UTI when the viruses are applied topically with a sponge.

A clinical trial for which Garofolo’s company is recruiting combines phage therapy with a first-line antibiotic; once they can demonstrate effectiveness with this combination, down the line studies can test the phages on their own for patients as a potentially life-saving treatment. “I always tell people that Hugh Hefner died from this,” he added. “A urinary tract infection can be quite frightening” for the millions of older adults who seek care for them each year.

These studies are critical, as is the integration of alternative therapies into clinical practice, as they have been shown to be safe and effective, German said. You could envision a future where patients use these interventions in tandem — preventing infections with vaccines, creams and probiotics, and treating infections that slip through the cracks with phages and first-line antibiotics.

“We need to devise new techniques and strategies to target the germs in the bladder and in the kidneys,” German said. “We are running out of antibiotics and the bacteria are evolving or outsmarting those antibiotics faster than we can provide them.”

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