UTI Treatment Is in Crisis

The way doctors treat urinary tract infections may be wrong, and antibiotic resistance is growing

UUrinary tract infections (UTIs) are one of the most common bacterial infections. By some estimates, 50% of all women experience a UTI in their lifetime, and half of those women will get more than one.

The infection is thought to be caused by gut bacteria like E. coli entering the bladder, resulting in feelings of pressure, discomfort, and pain, along with a nearly constant need to pee. If left untreated, the infection can move to the kidneys and, on rare occasions, can even turn deadly. Sex can sometimes contribute to the infection, but it’s not always the cause. Anything that results in bacteria coming into contact with the urethra increases risk.

A single course of antibiotics usually clears things up, but drug-resistant strains of bacteria are on the rise, making recalcitrant infections more common. Standard antibiotic treatments fail in 25% to 35% of people who take them, which worries doctors because antibiotics are the best and often the only way to treat UTIs. Some doctors are concerned that they may one day run out of options.

“Antibiotic resistance — not just [for UTIs] but all kinds of antibiotic resistance — is a huge problem, and no one’s really doing anything about it,” says Bradley Frazee, MD, an emergency medicine physician at Highland Hospital in Oakland, California, who recently published a study about the emergence of a particularly scary strain of drug-resistant UTI. “There’s not enough money in it, and if you talk about oral antibiotics for urinary tract infections, it’s even worse, because that’s [considered to be] kind of a ho-hum problem.”

The dramatic increase in resistant infections — up 8% and 15%, respectively, for two of the most common antibiotics over a 10-year period — has shifted the way Frazee and other doctors approach UTI treatment. When a person first presents with symptoms, the doctor typically prescribes a standard antibiotic while they wait for the urine culture results. But increasingly, doctors are noticing that cultures come back showing signs of bacterial resistance, and so the doctor has to prescribe a different drug.

Kalpana Gupta, MD, a professor of medicine at Boston University who helped write the Infectious Diseases Society of America’s guidelines on UTI treatment in 2010, says doctors are now trying to be more selective with the first antibiotic they prescribe. “You have to stop and with each patient say, ‘They have a UTI. What’s their risk of resistance? Did they get antibiotics recently? Have they traveled recently? Did they have a resistant organism before?’ Then you make almost an individual risk assessment in your patient for resistant organisms, and you base your UTI therapy on that,” Gupta says. “It’s really changed the way that we approach treatment of UTI.”

InIn September 2016, Marie — who requested that her full name not be included for privacy reasons — awoke with symptoms of a UTI. Marie, who was 29 at the time, went to her doctor and got a single dose of Monorul — also called fosfomycin — a broad-spectrum antibiotic that can treat uncomplicated urinary tract infections. When that didn’t help, Marie went back two days later and was prescribed Bactrim, a type of trimethoprim antibiotic that was commonly used to treat UTIs in the 1980s until resistance increased. Recent reports show that one in three UTIs do not respond to trimethoprim.

By the next day, things had gotten worse, and Marie had a fever and signs of a kidney infection. This time, her doctor prescribed a course of Cipro, which is in the fluoroquinolone family of antibiotics and has replaced trimethoprim as the first-line offense against UTIs. Over the past 20 years, however, resistance to fluoroquinolones has also increased, and in some regions, 20% of infections don’t respond to the antibiotic.

Marie’s symptoms started to improve while taking Cipro, but she still wasn’t completely better, and bacteria remained in her urine, so her doctor gave her a final 30-day dose of nitrofurantoin, which is becoming the new preferred treatment for UTIs as only 3% of bacteria are currently resistant to it. The last round of antibiotics seemed to do the trick, but Marie continued to get UTIs every couple months for the next two years.

“Antibiotic resistance — not just [for UTIs] but all kinds of antibiotic resistance — is a huge problem, and no one’s really doing anything about it.”

“It was really frustrating,” Marie says. “At certain points, when you realize you still have symptoms, you think, ‘Can it be possible? Am I just being overly sensitive?’ But then the tests confirmed that I wasn’t.”

To James Malone-Lee, MD, an emeritus professor of nephrology at University College London, Marie’s experience was the worst possible way to treat a UTI. The number one driver of resistance is antibiotic use itself, so by prescribing multiple types of antibiotics, her doctor may have inadvertently enabled several resistant strains to take hold, he says.

“In an environment where there’s resistance and you expose populations of microbes to antibiotics, many of them will be able to switch on genes that they’ve had for millennia which will prevent them from being affected by the antibiotic,” Malone-Lee says. “The answer is to shepherd your resources and not do crazy things like switching antibiotics… or using small doses or stopping treatment when people are only partially treated. Those are basic Darwinian approaches that could make a heck of a difference.”

DDoctors and scientists used to think urine was sterile, so they assumed the bacteria that grew in a urine sample must be causing infection. Over the past several years, however, research has revealed that, like the gut, the bladder has its own microbiome. This means it’s totally normal for a urine culture to show different bugs, including E. coli, which is typically blamed for UTIs. As a result, it’s virtually impossible to tell which bacteria in a urine culture are supposed to be there and which are causing an infection.

Many women with chronic infections show different results with each culture. “Every time I get a culture test, it’s a different bacteria,” says Carole Wilson, 61, who’s had a chronic UTI for 17 months. “Some are E. coli based, but it’s never the same,” she says.

And each culture result has required a different drug. So far, Wilson has had 56 courses of antibiotics since she was first diagnosed in December 2017. She says that she and her daughter worry that if she catches another type of bacterial infection, like pneumonia, doctors won’t have any antibiotics to treat it. But if she doesn’t continuously treat the UTI, she’s at a high risk for complications like sepsis.

Malone-Lee — who researches and treats women like Wilson with persistent treatment-resistant symptoms — takes an unorthodox approach to UTIs. Instead of treating the bacteria identified in the urine culture and changing antibiotics in an attempt to hit a moving target, Malone-Lee prescribes all of his patients the same first-generation antibiotic, cephalexin (brand name Keflex), which is a type of cephalosporin antibiotic. He never changes the prescription, and he ignores the urine culture. He only stops treatment after the women are completely symptom-free and have no other signs of infection in their urine, like white blood cells or pus. This might mean that some women are on the same antibiotic for years.

With this approach, Malone-Lee says he leaves more healthy bacteria intact, which he believes helps fight off the resistant bugs through natural competition. While the women’s urine cultures do show an initial increase in bacteria that are resistant to the drug, he says the levels quickly plateau. Malone-Lee doesn’t believe there’s a connection between the resistant bacteria in the culture and the infection anyway, since there’s no way of telling which bugs in the bladder aren’t supposed to be there, so he stays the course until his patients have no symptoms. So far, he’s treated hundreds of women this way with positive results.

“If we want to minimize the problems caused by [resistance], we should turn away from the cultures and just manage people on first-generation narrow-spectrum urinary antibiotics and judge the matter on their response and side effects,” Malone-Lee says.

This tactic makes sense to Alan Wolfe, PhD, a professor of microbiology and immunology at Loyola University Chicago who was one of the first scientists to publish on the bladder’s microbiome. He says that until testing methods become more precise and physicians can pinpoint the exact strain causing the problem, less aggressive treatment is better for bladder health.

“You want to use a narrow-spectrum antibiotic that only works on specific pathogenic bacteria,” Wolfe says. “Physicians try to wipe them all out and sterilize the bladder, but the bladder shouldn’t be sterile. Wiping out good bacteria actually leads to more resistance.”

While doctors work out new treatment recommendations, people like Wilson are trying to keep a positive attitude and soldier on. “It could totally ruin my life if I allowed it to,” she says. “But I won’t let it have that level of control over me. I try and manage it in some way.”

Health and science writer • PhD in 🧠 • Words in Scientific American, STAT, The Atlantic, The Guardian • Award-winning Covid-19 coverage for Elemental

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