Nanell Mann began getting urinary tract infections in 1971, when she got a hysterectomy following the birth of her sixth child. She would take antibiotics and get better. Get sick again. Take antibiotics. Not get better. Take other antibiotics. Repeat, repeat, repeat for more than 40 years—the list of treatments that worked against her infections getting shorter and shorter and shorter over time. Her UTIs became resistant to multiple antibiotics. And she kept getting sick.
Now her recurrent UTIs are so frequent and so difficult to treat that she has to plan her life around them. “I know every bathroom in every place I shop,” Mann, who is 82 and lives outside Salt Lake City, told me. She tries not to go anywhere she doesn’t know, because UTIs can lead to frequent and intense urges to urinate, along with pain, fatigue, headaches, and sometimes even a deadly infection of the kidneys.
Mann’s case might be remarkable for its duration, but she is part of a growing and worrying trend: More and more UTIs are becoming resistant to antibiotics. And in these cases, doctors are finding it difficult to treat what were once easily cured infections. “They kind of give up on you because they don’t know what to do,” Mann said. She was frustrated and desperate and in pain.
In 2012, Mann got in touch with Matt Mulvey, a microbiologist at the University of Utah. Mulvey had published a few papers on bacteria that cause UTIs, and patients were frequently emailing him for help. “I always feel bad,” he says, “because I feel very unable to help them.” But Mann was unusually persistent—as well as unusually nice, Mulvey says—and the relationship turned into a multiyear, single-patient study. Over a period of five years, Mulvey and his collaborators collected and sequenced urine samples from Mann when she got UTIs.
All of Mann’s UTIs during that five-year period turned out to originate from a single strain of E. coli known as ST131, commonly found in drug-resistant UTIs. But where was Mann getting the same strain from over and over again? The team decided to sequence Mann’s fecal samples too, and found a match: The bacteria causing her UTIs were also hiding out in her gut.
Researchers debate whether bacteria that cause recurrent UTIs come from the bladder or the gut, says Felicia Lane, a urogynecologist at UC Irvine who was not involved in the study. The study does not rule out the bladder as a reservoir for bacteria, but it does bolster a link between UTIs and the gut microbiome. And the link, if real, points to another way to treat UTIs that has recently gained traction: fecal transplants. “We’re definitely in need of new treatments,” says Lane, who led a small clinical study on fecal transplants in patients with recurrent UTIs. Lane’s preliminary data on 10 patients found that the fecal transplants reduced UTIs at three months—but they were no silver bullet. The effects seem to wear off at six months, suggesting the gut microbiome might need to be replenished regularly.
The study also got Mulvey to wonder why the same E. coli are able to survive in Mann’s gut. Whenever she went to the hospital with a UTI, her doctors cultured the bacteria from her urine and tested the bugs against various antibiotics. They prescribed a drug that worked, and her infection would clear. But the genetic data suggest that some E. coli kept surviving in the gut even when Mann’s UTI went away. Mulvey thinks the bacteria may be able to enter dormant states to hide from antibiotics, and targeting this behavior might help treat these recurrent infections.
Mann, for her part, has tried everything she can—from the doctor-ordered surgery that separated her colon and bladder wall to cranberry supplements to treatments like colloidal silver, which made her doctors wary. She’s not alone in her frustration. The failure of antibiotics and the lack of approved alternatives has driven patients to Facebook groups and Reddit forums, where they discuss unapproved cures such as apple cider vinegar and essential oils. In one way, drug-resistant recurrent UTIs are a glimpse into an antibiotic-free future.
Of course, that world is not so unfamiliar to Mann. “Remember, I was born before antibiotics,” she reminded me at the end of our conversation. (She was born in 1936, and antibiotics only became widely available in the 1940s.) In just the span of her lifetime, antibiotics have gone from a miracle cure to—in some cases—utterly useless.
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