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I’m told you always remember your first. I was 17, and my boyfriend and I had recently started having sex. It was a summer day in Los Angeles, both my parents were at work, and as I lay around my childhood home in an amorous haze, I found myself returning with ominous frequency to the bathroom. I stared at the underwear around my ankles while urine trickled into the toilet bowl, the muscles of my pelvic floor straining. It felt like trying to pass broken glass. After a few hours, I fainted in the bathroom. I went to my mother, weepy and panicked, and she explained that I probably had a urinary tract infection, or UTI. We went to urgent care, where I was given pain relievers and a prescription for antibiotics. My symptoms vanished within a day, a feat of modern medicine that made me grateful for the pharmaceutical industry. Over the next decade or so, however, my UTIs would return at vengeful, ever shorter intervals.
At one point, I was going to urgent care with UTI symptoms every four to seven weeks. I didn’t have a primary-care doctor, so I saw a rotating cast of urgent-care physicians. I was always given a prescription for antibiotics. Because I was embarrassed to return to the same place too many times, I sometimes switched up which urgent care I visited — the one 10 minutes away, 15 minutes away, or 20 minutes away — although I was honest about how often I was unwell. Even when I didn’t have a UTI, the antibiotics I took invariably gave me a yeast infection, and my body felt like it had been thrown into a semi-permanent state of sickness that medication wasn’t able to reach. It’s not just me. For more and more patients, getting a single UTI leads to a recurrent cycle of infections that can last for years.
UTIs are one of the most common infections among women; at least 30 million prescriptions are written for them every year. These drugs, however, are becoming less effective. One study found that more than 92 percent of bacteria that cause UTIs are resistant to at least one antibiotic already, and almost 80 percent are resistant to at least two.
Rising rates of antibiotic resistance means UTIs are becoming an increasingly difficult infection to treat. Between 1990 and 2019, the number of cases worldwide increased by 60 percent. Hospitalization rates have also risen dramatically: Now, the infection lands over 600,000 people in the hospital in the U.S. every year. Though usually regarded as a nuisance, albeit a painful one, UTIs are turning into a complicated illness for a growing number of the population. It turns out the way we treat them may be part of the problem.
Urinary tract infections are thought to occur when bacteria, usually E. coli, gets into the urethra, the bladder, or some other portion of the urinary system and colonizes it. People with vaginas are more prone to UTIs because their urethras are shorter, which makes it easier for bacteria to move up the urinary tract. While not strictly considered sexually transmitted, sex creates ample opportunity for bacteria to enter the urethra and can be a contributing factor to infection. Up to 8 percent of UTI cases every year in the U.S., or approximately half a million infections, result from E. coli from farmed turkey, chicken, and pork. In these cases, bacteria that may already be drug-resistant is transferred directly into the gut microbiome of human consumers.
UTIs can be barely noticeable for some people and excruciating for others. Most are accompanied by stomach- and backaches, pain while urinating, and insistent pressure to use the bathroom, even when there’s nothing left to expel. If the infection worsens, fever, vomiting, or even kidney infection can follow. After a single UTI, between 30 and 44 percent of women will experience a second infection; for women who have already had two UTIs within six months, half will go on to develop a third.
Certain prevention advice is common, and I heard plenty of it while I cycled in and out of urgent care: Urinate immediately after sex, don’t sit in a wet swimsuit, wipe properly when using the bathroom. Even all of these practical measures won’t prevent a UTI, however. Researchers now think that one of the best predictors for getting a UTI is simply having had one before.
“Here’s the thing that frustrates me,” says Dr. Scott Hultgren, a professor of molecular microbiology and the director of the Center for Women’s Infectious Disease Research at Washington University. “The advice from the doctor for women getting UTIs over and over and over is ‘you’re wiping wrong.’ That’s not what’s happening! It’s nothing to do with wiping or hygiene. It’s the nature of the disease.” Hultgren gets emails every week from women desperate for answers. So does Dr. Kalpana Gupta, an infectious-disease specialist and professor of medicine at Boston University who has spent more than two decades researching how to improve the treatment and prevention of UTIs. Some of these women ask her if showering before and after sex will help. “Especially in otherwise healthy adult women, when they have recurrent episodes of UTI, I think the most important thing is for them to understand that it’s not their fault; it’s not something that they’re doing,” Gupta says. “We really need to do our best to help people realize that it does not mean that they’re dirty or there’s something wrong with them.” The bacteria that causes UTI is present at the microbial level. “It’s not as simple as just washing this away,” Gupta adds.
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.
But overall, Rohn says, “we need scientific research into why the infection comes back for some and not others. If we start to understand how it works, we can design better therapies.”
When I was curled up in agony over a UTI, I often wondered what women did before modern medicine, but the infections of years past were probably quite different than the kind contracted from the world we live in today. That’s not only because the bacteria in our bodies is more resistant to antibiotics — it’s because of changes to our diet, our time spent outdoors, and even the surfaces we come into contact with, according to Melby. She co-authored a paper published last April arguing that our modern built environment — characterized by synthetic materials like concrete, plastic, drywall, and hermetically sealed buildings — is making us sicker by reducing the microbial diversity essential for human health. “We spend 90 percent of our time indoors. It’s not only that we’re getting exposed to unhealthy microbes, but that we’ve decreased our exposure to healthy ones,” Melby explains. “We are surrounded by surfaces that are primarily plastic and covered in all sorts of microbes that normally don’t have much to do with humans.”
Last April, the FDA approved a new antibiotic to fight UTIs for the first time in 20 years: pivmecillinam, a derivative of penicillin, which has already been in use in Europe for several decades. The hope is that pivmecillinam will be able to address infections that have become resistant to other oral antibiotics already available in the United States.
Rohn’s lab is hoping to advance to the first clinical trial of a novel microcapsule therapy that delivers antibiotics directly into the cellular lining, where they can attack potentially hidden pathogenic bacterial reservoirs. Hultgren, meanwhile, has developed a UTI vaccine that doesn’t rely on antibiotic agents; it’s currently ready to enter phase 2 clinical trials. Ideally, he says, this treatment would become the first-line therapy for UTIs. He’s also working on a complementary, fast-acting therapy that would use a molecule to prevent bacteria from sticking to the bladder wall.
In the end, an antibiotic did help me — once I was finally prescribed the right one. I had been on and off different antibiotic courses for about a year when a doctor suggested I take a lab test for a bacteria called ureaplasma, to see if it was contributing to my UTIs. I had tested positive for pathogenic E. coli before, but more recent lab work — when I was given it — didn’t indicate the bacteria was responsible for my symptoms. Much of the time, ureaplasma is harmless, though it can cause urinary tract infections if it proliferates. Perhaps, after a year of antibiotic use, a mostly harmless bacteria had gotten the better of me.
After specifically treating the ureaplasma, instead of being prescribed another antibiotic targeting E. coli, I haven’t had a UTI in months. First I was relieved. Then I was furious.