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above half of the women and more than one in 10 men will develop a urinary tract infection (UTI) in their lifetime, with many people suffering from recurrent UTIs. These common bacterial infections that can cause 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 drugs used to treat them — a number of antibiotics routinely used for UTIs have become ineffective, leading to more severe illness, hospitalization and mortality, and soaring medical costs drives.
Antibiotic resistance occurs naturally, but the use and misuse of antibiotics in humans and livestock has accelerated it. A 2019 study found that more than 92 percent of the bacteria that cause UTIs are resistant to at least one common antibiotic, and nearly 80 percent are resistant to at least two. Escherichia coli is the most common cause of UTIs.
“Antibiotic resistance is a big problem for UTIs compared to other infections because UTIs are so common. Therefore, we are seeing the impact 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 occurs when bacteria, viruses, fungi and parasites become unresponsive to the drugs used to treat them. In 2019, about 4.95 million deaths were linked to AMR, and at least 1.27 million people died as a direct result of antibiotic-resistant bacterial infections, according to a 2022 study published in lancet found. AMR killed more people than HIV or malaria in 2019 and was one of the leading causes of death worldwide, according to the study. In 2021, the World Health Organization (WHO) named AMR as 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, explains Bebell. In theory, if the right antibiotic is given at the right dose for a long enough period of time, it will kill any bacteria it targets. But antibiotics are not always prescribed or taken correctly. If the dose is too low or the antibiotic is not taken long enough, this puts the bacteria under selection pressure, but does not kill them completely. Those that survive adapt and become more resilient.
Even when antibiotics are properly prescribed and used, each time they are taken, they affect the composition of bacteria in the body and put selective pressure on those who live in the gastrointestinal tract — including E. coli and other bacteria that cause UTIs. So there’s a link between taking antibiotics in general and the possibility of later developing a drug-resistant UTI, says Bebell.
Humans can also be exposed through 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 E. coli by eating improperly cooked meat. This bacterium can cause intestinal disease, potentially leading to a drug-resistant urinary tract infection.
When a UTI does not respond to a traditional antibiotic, doctors turn to broad-spectrum antibiotics that are effective against a wider variety of bacteria. These are often only available intravenously and therefore require a hospital stay, which can last five to 14 days, and higher medical costs. Some people have died from UTIs that spread into the bloodstream and caused sepsis, and drug-resistant infections could make this more common.
Bebell recently had a patient with a drug-resistant UTI that required intermittent hospitalizations for several months. The patient’s blood and urine were cultured repeatedly to determine which bacteria were resistant to which antibiotic, allowing their healthcare provider to determine the most effective treatment. This raises the question of whether routine bacterial cultures should become the norm in UTIs. In such cultures, bacteria are isolated from urine and grown in a laboratory to determine what type they are and what antibiotics they are resistant to.
Although bacterial cultures are likely to become routine, especially in complicated cases, Bebell only sees them as a short-term solution. Bebell adds that while culture-based diagnosis is important, it’s also expensive and time-consuming (between one and five days), which can delay treatment. “I would like to see more point-of-care tests developed that can help identify the bacteria involved and their genetic make-up. I think the long-term strategy is to get better diagnoses 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 whether they have genetic mutations that indicate antibiotic resistance. Such tests, which could be performed in 15 minutes at the patient’s bedside by someone with little training, are in development, Bebell says. But she is not aware of any that are available for clinical use in urinary tract infections.
But better diagnostics alone will not solve the problem; New treatment strategies are also required. Last October, researchers found that a combination of the drugs cefepime and enmetazobactam was effective in treating some drug-resistant UTIs. Enmetazobactam essentially serves to protect cefepime from being destroyed by enzymes produced by drug-resistant bacteria. Bebell says combining one drug with another that “protects” it is a common strategy. “It’s promising in the long term because it’s the way we’ve had success with many of our combination antibiotics. But this particular antibiotic [combo] will be one of many, and I think a short-term fix in that sense,” she says.
New antibiotics could help. But Laxminarayan doesn’t believe that developing new drugs is the only answer to drug resistance, which is a global problem with no easy solution, he says. “It really requires that we use less antibiotics in raising poultry and pigs. It requires us [using] fewer antibiotics sprayed on trees. It requires better infection control in hospitals. It’s a whole range of things,” says Laxminarayan. “This isn’t the sort of thing that’s only amenable to a magic bullet, where you do one thing and then you’re done.”
“New antibiotics are on the way. But they will cost a lot of money,” he adds. “We’re used to spending $5, $10, $20 on antibiotics. Do we really want to spend $5,000 on the next course of antibiotics? Because that would mean that many people could not afford them. This puts a huge strain on the healthcare system. But this is where we are headed.”
When it comes to avoiding UTIs, Bebell says there aren’t many evidence-based strategies. (In particular, drinking cranberry juice, for example, shows no clear benefit.) The few evidence-based methods of prevention are staying hydrated, continuously flushing the system, and performing regular genital hygiene. (Bebell advises against washing too much and avoiding harsh soaps.) For people with female urinary tracts, urinating after sex can be helpful.
Because there aren’t many evidence-based prevention strategies, Bebell says the focus should be on antibiotic stewardship: reducing overall antibiotic use — not just in humans but also in commercial agriculture — and better infection control in hospitals and among the general public. The WHO states that some simple strategies to avoid infection include “washing hands regularly, preparing food hygienically, avoiding close contact with sick people, [practicing] Keep safe sex and immunizations up to date.”
“Often antibiotics are really needed, but we all have to work for them [proper] use of antibiotics, and each person has a responsibility,” says Bebell. “And I would encourage patients when they go to their doctor to ask even one simple question, ‘Do I need this antibiotic?'”
