Why aren't there better treatments for cystitis?

Women are routinely dismissed when they report symptoms of urinary tract infections, though the consequences can be severe.

For Melissa Wairimu, a video editor in Nairobi, the symptoms started at the age of 21. She was having to urinate constantly, and it burned when she did. Her back hurt as well.

A urine culture test diagnosed her with a urinary tract infection (UTI). "I didn't even know there was something called a UTI at that point," Wairimu says. She was prescribed a broad-spectrum antibiotic for seven days, and told to drink plenty of water to flush things out.

But the symptoms kept coming back, sometimes stronger. The pain in Wairimu’s back spread to her abdomen. She felt tired constantly, yet it was uncomfortable to lie down. “You have that prickly feeling that you have to go to the washroom,” she explains. It would keep her awake. And the inability to sleep worsened the fatigue, which made it hard to keep to her tight work schedule.

Wairimu feels that her doctors didn’t listen. She was told that her UTIs might be caused by sex – though she wasn’t having sex. Doctors seemed in a hurry to make assumptions and prescribe different antibiotics, yet these didn’t resolve the problem. One antibiotic even caused seizures. 

Wairimu is sympathetic to the six doctors she saw over the years, who she believes didn’t have enough training on recurrent UTIs. So she had to search out her own information, trawling through the internet and resonating with stories of people in similar situations. This led her to the patient advocacy group Live UTI Free, where she now works.

Wairimu began tweaking her diet and doing a lot of trial and error to see what would keep her symptoms at bay. Four years on, the problem is still lurking, but the symptoms are more manageable.

Visiting doctor after doctor. Not being taken seriously. Getting prescribed treatments that work only in the short term, if at all. These are the shared experiences of Wairimu and others experiencing "complicated UTIs" – defined as those that carry a higher risk of treatment failure – with an estimated 250,000 cases per year in the US alone. Many patients, clinicians and researchers alike are frustrated that there hasn’t been more progress in combatting both regular UTIs and these trickier forms, but they are holding out hope for change.

Poorly understood

The symptoms of a UTI include pain or burning while urinating, frequent or sudden pressure to urinate, passing urine that is cloudy, bloody or smelly, pain in the back or lower abdomen and fever or chills.

Typically, this is caused by E. coli. Many other bacteria can also be culprits, but there’s limited research on these – and even on rarer strains of E.coli, according to Jennifer Rohn, who heads the Centre for Urological Biology at University College London, UK.

A UTI can then cause cystitis, or inflammation of the bladder, explains Chris Harding, a urologist at Freeman Hospital and Newcastle University in the UK. There are other types of UTIs, but cystitis is the most common.

UTIs in general are extremely common, affecting at least half of women at some stage in their lives. They’re especially frequent among young, sexually active women and post-menopausal women, Rohn says. Genetics, hormones, and anatomy all come into play. Women and girls are especially affected because they have shorter urethras than men, and thus bacteria can reach the bladder more easily. While UTIs are classified as an infectious disease, they’re not contagious. However, the bacteria responsible can be transmitted from person to person during sex.

But men can get UTIs, especially when they’re older. In care homes, UTIs are the most common type of infection. Globally, UTIs affect an estimated 150 million people every year, but this already-pervasive issue is bound to become even more common as the world continues to age. "It’s a very large reason why elderly people end up in hospital," Rohn explains.

Because UTIs are common and usually uncomplicated, many medical providers dismiss them as a normal part of being a woman. But that risks trivialising the more severe cases, which are numerous. One estimate is that, like Wairimu, 25% of women with at least one UTI will go on to have recurrent UTIs: at least two in six months, or three a year. Many have even more.

As well as recurrent UTIs, there’s increasing awareness of chronic UTIs – sometimes referred to as long-term or embedded UTIs. Essentially, some people live with symptoms constantly. Yet there’s almost no official recognition of this condition.

Even relatively straightforward UTIs get missed as often as they get spotted. The typical methods for diagnosing UTIs are dipstick testing of urine and mid-stream urine cultures, but these aren’t sensitive enough to be reliable. In contrast, newer-generation molecular tests are almost too sensitive, picking up any pathogen even if it isn’t linked to the problem. They’re also expensive.

Urine testing is "cheap as chips," in Rohn’s words, but often misleading. The urine culture test – which involves growing the bacteria from a urine sample in the laboratory – was developed in the 1950s with pregnant women who had kidney infections. In other words, a standard test for UTIs derives from outdated research that was for a different part of the urinary tract.

"If you rely on urine cultures to make a diagnosis, you might miss around half of all UTIs," Harding says.

As with testing, medical education on UTIs remains out of date. Harding learned as a medical student that the bladder was a sterile environment. This popular misconception has led to confusion over how to interpret evidence of bacteria in the bladder. To this day, Rohn lectures medical students who believe, incorrectly, that urine is sterile.

While researchers are aware of the inadequacy of the tests, "it’s not filtered down into clinical practice", says Carolyn Andrew, a director of the Chronic Urinary Tract Infection Campaign (CUTIC), a patient advocacy group in the UK that is calling for clinical guidelines related to chronic UTIs.

Like many long-term sufferers of UTIs, Andrew was misdiagnosed at first. The retired lecturer was on a road trip when she became desperate for the loo, where she started feeling a burning sensation. Eventually "I was literally weeing every 15 minutes". The UTI tests came back negative, and Andrew was diagnosed with interstitial cystitis (IC), or bladder pain syndrome. The treatments for IC were painful and made things worse.

The following year, when she saw a specialist, she was finally treated for chronic UTIs. "Thank god someone is listening to me," she remembers thinking. It would take nearly four years of antibiotics to clear up the embedded infection, but Andrew remains grateful.

Andrew believes that a diagnosis based on symptoms rather than ineffective tests would have given her some answers earlier on. Rohn points out that symptom-based diagnosis is especially common-sense for people with repeat UTIs, as they can recognise their own bodily indicators. "Maybe we can start taking women and their symptoms more seriously," Rohn hopes. (Read more from BBC Future about the inequality in how women are treated for pain.)

Stigma and neglect

Rohn believes that a "perfect storm" of perceptions explains why UTIs have been so neglected: "It’s a woman’s disease. It also affects the elderly. And it’s down there," she says.

"There probably still is a level of shame attached," says Andrew. Especially for older people or people from certain communities with taboos around discussing bladder issues, it can be hard to mention the symptoms. "Particularly in Africa, there’s not much talk about it," says Wairimu. “It’s hush hush.”

There is undeniably a gendered element as well. "Women are told they’re dirty," Andrew fumes. "One of the most upsetting things about this is that a lot of women are told that their hygiene habits are unacceptable and that they’ve caused it themselves."

Many people with complicated UTIs have had similar experiences of being misdiagnosed, talked down to, or gaslit. They are often told that their symptoms are all in their heads. Some are even shouted at by their doctors.

"It’s also perceived as being very minor," Rohn notes. Because UTIs aren’t typically fatal, they don’t attract the same levels of funding and attention as other infections. But UTIs can lead to death via sepsis or kidney infection. "People don’t realise that bacterial infections are very dangerous if they aren’t treated properly," she says.

These infections can be not only dangerous, but also deeply damaging the personal and professional lives of those affected. Andrew lived with constant pain and pressure on her bladder before she was finally treated for a chronic UTI. In her work with CUTIC, she’s seen people so desperate that they ask to have their bladders removed.

And as challenging as UTI cases can be in adults, the challenges are magnified when treating children. For example, symptoms are often ambiguous in very young children, and getting an uncontaminated urine sample can be a challenge. Some parents who come to CUTIC report that children as young as three are experiencing UTIs.

The antibiotic dilemma

For those lucky enough to be accurately diagnosed with a UTI, treatment can be a minefield. In Kenya, antibiotics were prescribed almost indiscriminately for Wairimu. In the UK, the standard course of antibiotics for treating UTIs in women lasts three days. For men, whose cases are automatically considered complicated, the default period is seven days. The disparity is frustrating for some.

Rohn believes that the standard three-day period, with the limited slate of antibiotics on offer, isn’t enough for many women. A key reason for the limited treatment duration is concern over antimicrobial resistance. This is justified, but too often a preoccupation with antimicrobial stewardship neglects people who are suffering, Rohn argues. "Stewardship’s not meant to stop treatment. It’s meant to stop inappropriate treatment."

One paradox is that insufficient first-line treatment of UTIs can turn these infections chronic or recurrent, with tenacious bacteria hiding within biofilms. In these cases, ultimately more antibiotics may be required. For recurrent UTIs, patients are often treated with longer courses of antibiotics. This happened to Andrew, who dipped between private and public healthcare before she found relief. Many others wouldn’t have the resources or the education level to persist in seeking better care.

Prospects for change

A number of efforts are underway to improve diagnosis and treatment of UTIs. In response to antibiotics losing their power, researchers are trying to repurpose existing drugs or increase their penetration into the tissues where they’re needed. Last year, pharmaceutical company GSK also reported promising test results for a new oral antibiotic. If approved, it would be the first one developed in over two decades to treat uncomplicated UTIs.

Given the enormous problem of drug-resistant superbugs, alternatives to antibiotics are needed as well. Harding offers patients vaginal oestrogen supplementation as one non-antibiotic option, but there are promising signs that antiseptics might also work.  

In March 2022 , together with colleagues from across the UK, Harding published the results of a study examining the effects of a urinary antiseptic on patients who were experiencing, on average, seven UTIs a year. Unlike antibiotics, antiseptics are usually applied outside the body – though both work to inhibit the growth of microbes.

With this method, patients were instructed to take oral methenamine hippurate twice a day for 18 months. The idea is that the antiseptic salts turn into formaldehyde at the end of the kidney filtration process, killing off the bacteria that cause UTIs.

The research found that the antiseptic administered to the study group left them essentially no worse off than the control group, who received antibiotics. Harding hopes that the results will lead to methenamine being recommended in British and European clinical guidelines as a preventive measure for people with recurrent UTIs.

Several vaccines against UTIs are also in development. They’re furthest along in the UK, but even there are generally not accessible. “We’re excited by the opportunities presented by UTI vaccines for our patients but at this stage they all require further studies before we can make them widely available,” says Rajvinder Khasriya, who leads the UK’s only NHS clinic dedicated to chronic and recurrent UTI infections, where Andrew finally found relief.

Basic research also has an important role in illuminating the urinary tract. Rohn says that “mouse models have reigned supreme” in UTI research for many years, despite mice having different urinary functions to humans. Unlike humans, mice don’t store urine for a long time. Nor do they even get UTIs naturally.

Rather than relying solely on mouse-based models, Rohn and colleagues have designed a 3D model of a human bladder that can mimic the stretch and flow of the real organ, and be programmed with actual urine. "It’s quite exciting now being in a time when human modelling is entering a renaissance," Rohn enthuses.

In the meantime, a greater awareness of UTIs – and willingness to take them seriously – could go some way to alleviating the suffering of women like Wairimu and Andrew, who have had to struggle for years to find answers.

* This article was updated on 8 February 2023 to make clearer that the test for cystitis was originally developed for kidney infections, a different part of the urinary tract.

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