Urinary tract infections are increasingly becoming resistant to first-line antibiotics, and this may be a warning for our ability to treat other microbial infections

About half of women and more than one in 10 men will get a urinary tract infection (UTI) in their lifetime, with many people experiencing recurrent UTIs. These common bacterial infections, which can lead to painful urination, have been easily treated and cured with antibiotics for decades.

But as a result of antibiotic resistance—when bacteria become resistant to the medicines used to treat them—a number of antibiotics routinely employed for UTIs have become ineffective, leading to more severe illness, hospitalizations and mortality while driving up medical costs.

Antibiotic resistance occurs naturally, but the use and misuse of antibiotics in humans and livestock have accelerated it. One 2019 study found that more than 92 percent of bacteria that cause UTIs are resistant to at least one common antibiotic, and almost 80 percent are resistant to at least two. Escherichia coli is the most common cause of UTIs.

“Antibiotic resistance is a huge problem for UTIs, compared to other infections, because UTIs are so common. So we see the effects of antibiotic resistance much more immediately and with a higher prevalence,” says Lisa Bebell, an infectious disease physician at Massachusetts General Hospital.

Drug-resistant UTIs are a consequence of the larger problem of antimicrobial resistance (AMR), which happens when bacteria, viruses, fungi and parasites no longer respond to medicines used to treat them. In 2019 roughly 4.95 million deaths were associated with AMR, and at least 1.27 million people died as a direct result of antibiotic-resistant bacterial infections, a 2022 study published in the Lancet found. AMR killed more people in 2019 than HIV or malaria and was a leading cause of death globally, according to the study. In 2021 the World Health Organization (WHO) declared AMR one of the top 10 global public health threats facing humanity.

The bacteria that cause UTIs have become resistant for several reasons. One is selection pressure, Bebell explains. In theory, when the correct antibiotic is given in the right dose for a long enough period, it kills off all the bacteria it targets. But antibiotics are not always prescribed or taken correctly. If the dose is too low or the antibiotic is not taken for long enough, that puts the bacteria under selection pressure but does not kill them off completely. Those that survive adapt and become more resistant.

Even when antibiotics are prescribed and used correctly, every time people take them, they affect the composition of bacteria in the body and put selection pressure on those that live in the gastrointestinal tract—including E. coli and other bacteria that cause UTIs. So there is a connection between taking antibiotics in general and the possibility of later developing a drug-resistant UTI, Bebell says.

People can also be exposed by eating animals, says Ramanan Laxminarayan, an epidemiologist and chair of the WHO’s Global Antibiotic Research & Development Partnership (GARDP), a nonprofit organization dedicated to developing treatments for drug-resistant infections. He explains that they can get a drug-resistant strain of E. coli from eating improperly cooked meat. This bacterium can cause an intestinal disease, potentially leading to a drug-resistant UTI.

When a UTI doesn’t respond to a traditional antibiotic, doctors employ broad-spectrum antibiotics, which are effective against a greater variety of bacteria. These are often only available intravenously and therefore require hospitalization, which can last from five to 14 days, and higher medical costs. Some people have died from UTIs that spread to the bloodstream and caused sepsis, and drug-resistant infections could make this more common.

Bebell recently had a patient with a drug-resistant UTI who had to be hospitalized intermittently for many months. The patient’s blood and urine were cultured repeatedly to identify which bacteria were resistant to which antibiotic, enabling his health care providers to determine the most effective treatment. This raises the question of whether routine bacteria cultures should become the norm for UTIs. In such cultures, bacteria in the urine are isolated and grown in a lab to identify which type they represent and what antibiotics they are resistant to.

Although bacteria cultures are likely to become more routine, especially for complicated cases, Bebell says, she sees them as only a short-term solution. Bebell adds that while culture-based diagnostics are important, they are also expensive and time-consuming (taking between one and five days), which can delay treatment. “I’d like to see more point-of-care tests developed that can help identify the bacteria that’s involved and its genetic composition. I think the long-term strategy is to get better diagnostics and not rely on culture-based methods,” she says.

Bebell would like to see tests that can identify the main bacteria causing the infection and determine whether it has any genetic mutations that indicate antibiotic resistance. Such tests, which could be done at the patient’s bedside in 15 minutes by someone with little training, are in development, Bebell says. But she’s not aware of any that are available for clinical use for UTIs.

But better diagnostics alone won’t solve the problem; new treatment strategies are also needed. Last October researchers found that a combination of the medications cefepime and enmetazobactam was effective in treating some drug-resistant UTIs. Enmetazobactam essentially works to protect cefepime from being destroyed by enzymes produced by drug-resistant bacteria. Bebell says that combining one drug with another that “protects” it is a common strategy. “It’s promising in the long run because that’s how we’ve been successful with many of our combination antibiotics. But this particular antibiotic [combo] is going to be one of many, and I think a short-term solution in that sense,” she says.

New antibiotics could help. But Laxminarayan doesn’t believe new drug development is the only answer to drug resistance, which is a global problem with no easy fix, he says. “It really requires us using fewer antibiotics in raising poultry and pigs. It requires us [using] fewer antibiotics that are sprayed on trees. It requires us having better infection control in hospitals. It’s a whole bunch of things,” Laxminarayan says. “This is not the sort of thing which is amenable to just a silver bullet, where you do one thing, and then you’re done.”

“New antibiotics are on their way. But they will cost a huge amount of money,” he adds. “We’re used to spending $5, $10, $20 for antibiotics. Do we really want to spend $5,000 for the next course of antibiotics? Because that would mean that many people would not be able to afford those. It places a huge strain on the health system. But that’s where we’re headed.”

When it comes to avoiding UTIs, Bebell says there aren’t a lot of evidence-based strategies. (Drinking cranberry juice in particular, for example, doesn’t show a clear benefit.) The few evidence-based prevention methods are to keep hydrated to continually flush the system and to perform regular genital hygiene. (Bebell advises against washing too much and says to avoid harsh soaps.) For people with a female urinary tract, she says, it may be helpful to urinate after sex.

Because there aren’t many evidence-based prevention strategies, Bebell says, the emphasis should be on antibiotic stewardship: a reduction in overall antibiotic use—not only in humans but also commercial agriculture—as well as better infection control in hospitals and among the general public. The WHO notes that some simple strategies to avoid infections include “regularly washing hands, preparing food hygienically, avoiding close contact with sick people, [practicing] safer sex, and keeping vaccinations up to date.”

“Often antibiotics genuinely are needed, but we all need to be advocates about [proper] antibiotic use, and every person has a responsibility,” Bebell says. “And I would encourage patients, when they go to see their health care provider, to ask even just one simple question: ‘Do I need this antibiotic?’”