As the threat of antibiotic resistance grows, researchers are developing ways to prevent recurrent and chronic urinary tract infections (UTIs) without antibiotics. UTIs disproportionately affect women and can cause debilitating symptoms. The latest approaches include an oral vaccine that in trials prevented recurrent UTIs for nine years, as well as the development of non-antibiotic drugs. Scientists are also testing safer ways to use antibiotics, which often cause side effects, to treat the infections.

“I’ve been on about five or six antibiotics and the one I’m on now is probably the only one that doesn’t give me really bad symptoms,” says Gemma Perry, aged 43, who has had a chronic UTI for 12 years and wants to raise awareness of the condition.

UTIs include bacterial infections of the bladder, kidneys and the tubes that connect them. Symptoms include a burning sensation when urinating, an urge to pee more often than usual, and abdominal pain. Around 40–60% of women have at least one infection in their life. Of these women, about 20% have recurring UTIs — at least two within six months, or at least three infections in a year.

UTI symptoms often disrupt Perry’s daily life. “When it was really bad, I was going to the toilet probably around 20 times in a day and I was in a lot of pain,” she says. “It’s horrendous.” Perry takes a daily dose of antibiotics that reduces the growth of bacteria that persist in her bladder. Most antibiotics she has tried caused side effects such as tingling fingers and an irregular heartbeat, she says. “The racing heart was probably the scariest.”

Promising vaccine

Researchers presented their latest results of the oral vaccine, called MV140, last month at the 6th European Association of Urology Congress in Paris. MV140 — developed by biotechnology company Inmunotek in Madrid more than a decade ago — contains four inactivated species of bacteria that commonly cause UTIs. The pineapple-flavoured vaccine is sprayed under the tongue daily for three months.

Urologist Bob Yang at the Royal Berkshire Hospital in Reading, UK, and his colleagues have been trialling MV140 since 2014, and early results showed that it could reduce the risk of UTIs for up to 6 months. The team tracked the medical records of 89 people who were vaccinated in 2014 — most of them women — and found that around half of them did not develop a UTI for up to nine years. “Over 50% of women remained infection free, which is excellent,” says Yang. “There weren’t any long-term side effects or long-term complications.”

“It’s really flabbergasting,” says Jennifer Rohn, a cellular microbiologist at University College London. Although the vaccine will not work in everybody because of the variation in how UTIs develop, it could benefit a lot of people, she says. Still, the study was small, has yet to be peer-reviewed, and focused on people with relatively simple UTIs, says Rohn. “It would be great to have more people, and more complicated cases tested.”

The team plans to test the vaccine on more complex UTIs, for example in people who have spinal injuries and have a raised risk of the infections for anatomical reasons. But it’s likely to be years before the vaccine is approved for wider use. “This won’t be a quick process,” says Yang.

Targeted treatments

In another conference talk, researchers showed that delivering the antibiotic gentamicin directly into a person’s bladder, rather than using oral antibiotics, can reduce antibiotic resistance among UTI-causing bacteria.

Urologist Pragnitha Chitteti at James Cook University Hospital in Middlesbrough, UK, and her colleagues treated 37 people — mainly women whose UTIs did not respond to low-dose antibiotics — with gentamicin. Trial participants were trained to infuse gentamicin directly into their bladders through a catheter. They received varying doses of gentamicin for months.

Before treatment with gentamicin, multidrug resistance was present in bacteria sampled from 44% of the people treated. After treatment, this dropped to just 10%. Moreover hospital admission rates among the participants dropped from 41% of people before treatment, to just 5% after treatment. And in 76% of people, the treatment reduced frequency of UTIs.

Antibiotic alternative

Other approaches to tackling antibiotic resistance include the use of a non-antibiotic drug called methenamine hippurate to treat UTIs. The drug was designed to prevent UTIs decades ago, but fell out of favour among urologists because of a lack of studies that directly compare its efficacy to that of antibiotics, says Ased Ali at the University of Newcastle.

In a 2022 study1 involving around 240 women, the medication cut the risk of recurrent UTIs similarly well to standard antibiotics. The findings spurred the European Association of Urology, which provides UTI treatment guidelines to clinicians across Europe, to strongly recommend the use of methenamine hippurate to prevent UTIs in people without anatomical abnormalities of the urinary tract. “That was fantastic,” says Ali. The UK National Institute for Health and Care Excellence, which creates guidelines for physicians, is also considering updating its guidance, says Ali.

Perry knows that it could take years before improved therapies are widely available. “I’m aware that throwing antibiotics down my neck is not ideal, but I’ve got no other option.”

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