New Ways to Treat Common Urinary Tract Infections

Expanding treatment options

Three new medications approved in the past 14 months aim to address this growing problem of antibiotic resistance.

Blujepa: Most recently, the U.S. Food and Drug Administration (FDA) approved Blujepa (gepotidacin), the first of a new class of drugs for the treatment of uncomplicated urinary tract infections caused by E. coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus and Enterococcus faecalis in women and children age 12 and up. The oral medication is taken twice daily for five days, with the most common side effects reported being gastrointestinal issues like diarrhea.

Not since the 1990s has the FDA cleared a new class of antibiotics for UTI treatment, and this one, called triazaacenaphthylenes, works by targeting enzymes in bacteria like E. coli that help them proliferate. Triazaacenaphthylenes also inhibit DNA replication in other bacteria, like Klebsiella pneumoniae. Researchers say the medication could work to treat more patients who don’t respond to standard UTI treatment with the antibiotic nitrofurantoin.

Orlynvah: Blujepa’s clearance follows the FDA’s approval of the oral medication Orlynvah (sulopenem etzadroxil and probenecid) last October for the treatment of uncomplicated urinary tract infections caused by E. coli, Klebsiella pneumoniae or Proteus mirabilis for women who “have limited or no alternative oral antibacterial treatment options,” the FDA says.

“Orlynvah is more active against certain ‘smart’ resistant bacteria, especially those that produce enzymes called extended-spectrum beta-lactamases (ESBLs),” explains Renuga Vivekanandan, M.D., an infectious disease physician and associate dean for clinical affairs at Creighton University School of Medicine in Omaha, Nebraska.

“These ESBLs can make E. coli and other bacteria resistant to many common antibiotics. Orlynvah is an option to treat UTIs caused by these resistant bacteria, but only when there are symptoms of infection.”

A urine culture, which checks for bacteria and other microorganisms, is used to identify the type of bacteria causing a UTI. Based on that and whether a patient responds to standard medications, like nitrofurantoin or trimethoprim-sulfamethoxazole, their physician might consider a new medication.

The most common side effects reported with Orlynvah have been diarrhea, nausea, vaginal yeast infection, headache and vomiting. The medication should not be taken by patients who have uric acid kidney stones (since it may worsen gout, which is associated with kidney stones) or patients who are taking the pain medication Toradol to avoid increasing the risks associated with both drugs.

Pivya: Another new drug, a synthetic penicillin called Pivya (pivmecillinam), was approved in April 2024 to treat uncomplicated UTIs caused by bacteria that have become drug-resistant.

Vivekanandan and other doctors say they will still prescribe older antibiotics first but will consider newer drugs when those don’t work.

“I am happy to see we have newer drugs to keep in our arsenal and use as needed,” Vivekanandan says.

Beyond pills, scientists are looking at other ways to treat stubborn infections, including using nanotechnology to find and kill “hidden” bacteria that antibiotics can’t reach. (Previous research suggests that the UTI-causing bacteria enter urothelial cells — those cells lining the urinary tract, including the urethra and bladder — and hide within those cells.) Still, more research is needed.

Not all UTIs need to be treated

Specialists who treat UTIs say health care providers should consider timely treatments so patients can get on with their lives while also minimizing the risk of antibiotic resistance, which can make future infections harder to treat.

For example, a lot of older patients may have bacteria in their urine but no symptoms. “Those patients should not be treated — we call it asymptomatic bacteriuria — and as we age, the number of patients that have that increases,” Moore says.

“If we treat that bacteria without having symptoms, the biggest concern is that you get resistant bacteria. And when you truly get an infection, you need to have more powerful antibiotics,” Vivekanandan adds.

Doctors say that doesn’t mean all UTIs should be allowed to persist or go untreated. If an infection with symptoms is left untreated, a UTI can lead to a potentially life-threatening complication called urosepsis, a type of sepsis that begins in the urinary tract. Symptoms can include vomiting, chills, confusion or disorientation, and a rapid, raised heart rate.

“If we do have symptoms and don’t treat the infection, it can spread from the bladder to the kidneys and sometimes even to the blood,” Vivekanandan says. “So, when we are not feeling well, it’s important to seek medical advice and get the right treatment.”

Preventing UTIs

There are some things you can do to lower your odds of getting a UTI in the first place, including:

• Staying well hydrated
• Avoiding long baths — opt for a shower instead
• Not holding it in when you have to urinate
• Eating foods rich in probiotics, such as yogurt and sauerkraut 
• Peeing after sex
• Avoiding underwear that is too tight and made of material that doesn’t breathe
• “We want to be able to prevent infections rather than having to come up with all these novel drugs,” Moore says. “So prevention’s key.”