A ‘game-changer’ drug could prevent chronic urinary tract infections… yet many women still don’t get them

Susannah Fraser knew exactly what the arrival of a painful stomach ache, blood-filled urine and fever meant.

The debilitating symptoms heralded the arrival of her next urinary tract infection (UTI) and heralded the start of another six weeks of pain.

‘It’s unbearable – a white-hot, burning pain shooting through you,’ says Susannah, 55, a communications manager and mother-of-two, who lives with husband Neil, 58, in the West Midlands.

These infections, caused by bacteria entering the tube that carries urine from the body, occurred every two or three months for six years.

They left Susannah on the couch in pain for days because she needed regular sick leave from work. It also meant she and her family often missed outings with friends – a particularly brutal infection ruined a family holiday to Jersey.

About half of all British women will have at least one urinary tract infection at some point in their lives. This can affect the bladder (known as cystitis), urethra (the tube that carries urine out of the body) or the kidneys.

It’s one of the most common reasons for seeing a GP: About a million women in England have recurrent urinary tract infections, occurring twice every six months or three times a year, according to a 2015 study in the British Journal of General Practice.

Women are at greater risk of recurrent UTIs as they age (due to menopause and declining hormones); if they have had them in the past; after sex, or if they experience incontinence.

At the first sign of symptoms, Susannah would go to her GP, who would prescribe her a three-day course of antibiotics.

As the infections became more common, she was given a daily antibiotic pill to take for a long period of time to prevent further infections – in line with current official medical guidelines.

But although this reduced the number of infections, Susannah still had them about every four months.

Then, six years ago, her consultant put her on a new treatment, a twice-daily pill called methenamine hippurate, which sterilizes the urine and stops the growth of certain bacteria.

“It was incredible,” says Susannah. “I haven’t had a urinary tract infection in three years.”

A 2022 study in the BMJ found that methenamine hippurate is as effective as antibiotics in the long term at preventing urinary tract infections (preventing recurrent infections in 50 percent of cases) and that, significantly, it was not associated with antibiotic resistance and provided a treatment option for those who do not respond to antibiotics.

The research was hailed as a game-changer. But campaigners have told Good Health that many women who could benefit are not given the opportunity to try it. One problem is the fact that many GPs ‘have never heard of it; women are contacting Bladder Health UK to tell us,” says Susannah, who works for the charity.

And this is just one of many problems women with recurring UTIs face, experts say — including inaccurate diagnostic tools and guidelines for prescribing short courses of antibiotics.

Women also often describe feeling simply ignored by doctors.

Dr. Catriona Anderson, an NHS and private GP from Staffordshire who specializes in urinary tract infections, says: ‘Many women burst into tears on their first appointment with me purely because I listen to them and believe their symptoms.

“UTIs are often viewed and treated as a short-term problem,” she says, adding that shortcomings in diagnosis and care are “often due to a lack of knowledge among primary care physicians.”

The hunt for alternatives to antibiotics is driven by concerns that their overuse is creating “superbugs”: bacteria that develop resistance to the drugs used to combat them.

This puts patients at risk of persistent symptoms, more serious infections and sepsis, a potentially life-threatening response to infection, according to the charity Antibiotic Research UK.

An analysis of one million urinary tract infections in 2017 by Public Health England found that one in three patients was resistant to the antibiotic then used as a first-line treatment.

The 2022 methenamine hippurate study, led by Professor Chris Harding, a consultant urological surgeon at Newcastle Hospitals NHS Foundation Trust, involved 240 women with recurrent urinary tract infections. Half received methenamine hippurate and the other half a low dose of antibiotic.

Methenamine hippurate is converted to formaldehyde in the kidneys, creating acidic urine that acts as an antiseptic and kills the bacteria causing the infection. The drug also kills a range of bacteria in the urine, rather than targeting specific bacteria as antibiotics do. Crucially, bacteria do not appear to develop resistance to it.

Side effects were similar and mostly mild in both groups: 28 percent of those taking methenamine hippurate reported problems such as stomach upset and acid reflux, while 24 percent of those taking antibiotics reported side effects including diarrhea and nausea.

Methenamine hippurate had been licensed to treat recurrent urinary tract infections in women before the publication of Professor Harding’s research, but was not included in the treatment guidelines given to GPs by the National Institute for Health and Care Excellence (NICE). NICE announced it would investigate this again in August 2022, but there has been no update.

‘There are women who could benefit from trying them, and we know it is important to reduce our use of antibiotics to reduce resistance in bacteria,’ says Professor Harding.

‘We cannot guarantee that methenamine will be effective in all cases, but the majority of women in our study experienced a dramatic reduction in the frequency of urinary tract infections. This medicine is a very useful addition to the treatments we can offer.’

NICE told Good Health that a decision on the drug would not be published until November.

Meanwhile, another problem for women with recurrent urinary tract infections is not getting adequate antibiotic treatment. The problem is that the bacteria embed themselves in the cells lining the bladder and urethra, and reappear after the medication ends.

Many doctors worry that the standard treatment for a urinary tract infection – a three-day course of antibiotics – may be too short.

Dr. Rajvinder Khasriya, consultant gynecologist at Whittington Health NHS Trust in London, says: ‘For many patients it’s just not enough. And then you yo-yo back to the doctor for further treatment. And this occasional administration of antibiotics promotes the resistance of the bacteria that cause the infection.’

That’s why they use ‘a lot’ of methenamine in her clinic. “It suppresses the overgrowing bacteria and allows the good bacteria to come back,” she says.

‘But there seems to be a postcode lottery: patients say that some GPs will prescribe it, while others are unwilling or unable to do so.’ Approval from NICE would encourage more GPs to prescribe it, says Dr Anderson.

Another barrier to successful treatment is the standard tests – which involve a dipstick and urine culture – which experts say can miss infections.

The NICE guidelines state that most women under 65 can be diagnosed without testing, based solely on two urinary tract infection symptoms, such as pain, frequent urination and cloudy urine. But in less obvious cases (for example, those under 65 years of age and with only one symptom), a urine dipstick test may be used. This involves placing a strip of treated paper in a urine sample. A color change indicates high levels of nitrites (produced by bacteria) and white blood cells, which may be a sign that the body is fighting an infection.

‘The dipstick test is fast and cheap, but performs poorly at ruling out urinary tract infections and misses many infections,’ says Professor Jennifer Rohn, a cellular microbiologist at University College London.

‘It only looks for some of the bacteria that we know cause urinary tract infections. So if the dipstick is negative, the doctor may send you home without antibiotics and think you are not sick.”

Pregnant women, people aged 65 and over and patients with recurring symptoms must have a sample sent for laboratory testing (a so-called urine culture).

Analysis of any bacteria growing can indicate the type of infection and which antibiotics will kill it.

However, the current threshold used by the NHS to diagnose a urinary tract infection (100,000 bacteria per milliliter of urine) is “an arbitrary and high figure, developed from a small study 70 years ago”, according to Professor Rohn.

She adds that the standard advice for women with urinary tract infections to drink plenty of water also dilutes the urine and bacteria sample, and “dilutes the cells and bacteria that both tests look for.”

Campaigners and patients say this all adds to an ongoing struggle to get good care.

Susannah is relieved that the treatment has finally worked. “Taking methenamine has given me the confidence to go out and live my life again,” she says.

‘I really want GPs and other women to know it exists.’