#utis

There’s new research that shows why antibiotics aren’t working as well — and not just because they’re contributing to antibiotic resistance. In 2022, Hultgren published one of the first studies demonstrating that people who suffer from recurrent UTIs have a markedly lower diversity of beneficial gut microbes. This makes it easier for E. coli and other infectious bacteria to cause an “intestinal bloom” of UTI-causing pathogens long before they reach the urethra. While antibiotics might temporarily clear bacteria from the bladder, they leave pockets of these pathogens intact, which means they can stick around and cause another UTI. “One of the functions of the microbiota” — the community of bacteria, viruses, fungi, and other microorganisms living in the human body — “is something called colonization resistance. When there’s a decrease in diversity of the microbiota, it opens up habitats for E. coli to get in and gain a foothold,” Hultgren explains. “So antibiotics, even though they are a frontline therapy, are actually a risk factor for UTI.”

In another big breakthrough, researchers at University College London developed artificial “mini-bladders” from human stem cells, then documented how multiple strains of UTI-causing bacteria will burrow into the cellular lining. Once entrenched within the protective wall of the bladder, they can form pathogenic reservoirs that are inaccessible to oral antibiotics. “The immune system can’t get in there to clear it. Drugs can’t get in there to kill it. And then, if you give a urine specimen at your doctor’s appointment, if all of your bacteria is inside the bladder, it’s not going to come out in the urine,” says microbiologist Dr. Jennifer Rohn, who led the University College London study. “So your urine test is going to be negative.” Even before the skyrocketing antibiotic resistance we see today, Rohn explains, “antibiotics didn’t always work.” For the patients who experience UTI recurrence, Rohn says, “Some of that failure has nothing to do with antimicrobial resistance — the drugs fail because the bug evades them, which has always been the case.”

Other studies have highlighted just how complicated these infections really are. Another that Hultgren co-authored found that severe UTIs might fundamentally alter the epigenetic expression of DNA in the bladder, so that the immune system responds more aggressively to the next UTI. This overexuberant inflammatory response actually leads to a greater susceptibility to infection: As the body reacts with increasing hostility, UTIs become both more painful and more likely. Meanwhile, each round of antibiotics ravages the microbiome, creating more opportunity for drug-resistant bacteria to flourish when the immune system is already in overdrive. Last March, a team of scientists at Duke University working with mice found that repeated infections can trigger an overgrowth of sensitive nerves in the bladder and pelvis that cause persistent urinary-tract inflammation even when no bacteria is detectable, and they hypothesized the same underlying mechanism might be causing recurrent UTI symptoms in human patients. All this research underlines that recurrent UTIs require more than a traditional quick-fix prescription.

“It’s been almost 100 years since Fleming discovered antibiotics,” Rohn says. “That’s still the first-line therapy, and it fails around 30 percent of the time. What kind of a men’s disease would still be using a 100-year-old therapy that doesn’t work?”

This isn’t to say that antibiotics are never an effective treatment for UTIs. But the growing consensus among professionals in the field is that something needs to change. Gupta, the infectious-disease specialist, stressed that treating a UTI requires a solid patient-doctor relationship; one marked by attentive, thorough care and plenty of follow-up conversations. Some researchers specializing in UTIs have started advocating for a system of “informed consent” before administering antibiotics, which would include giving patients a thorough understanding of how the antibiotics might affect their long-term-health outcomes and the potential for UTI recurrence. “When you have limited time, there’s a temptation to just give them a prescription and move on,” says Dr. Melissa Melby, a professor of anthropology at the University of Delaware studying how human health and development is impacted by the environment. “Patients are asking for them as well — being told to just drink more water feels like they’re not taking you seriously. It would be better if doctors said, ‘I could give you antibiotics, but this is not a long-term solution, and it actually might make you more vulnerable to infections later on.’”

Another approach might be the “pill in the pocket” strategy, Melby explains, in which a patient is given an antibiotic prescription dated two to three days ahead. In the meantime, they’re advised to rest and drink lots of water. If the infection clears, patients won’t need to use the prescription; but if it doesn’t, they can still pick up antibiotics from the pharmacy. In a study conducted by researchers in Amsterdam, over half the women who opted to delay drug use saw improvements in their symptoms in a week.