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This is a plain English summary of an original research article. The views expressed are those of the author(s) and reviewer(s) at the time of publication.

The drug methenamine (which is not an antibiotic) could be as effective as antibiotics at preventing urinary tract infections. A recent study included women who had frequent infections of the urinary tract (the organs involved in peeing). In 12 months’ treatment, they had similar reductions in these infections, whether they received methenamine or an antibiotic.  

Recurrent urinary tract infections are generally treated with daily, low-dose antibiotics. However, taking antibiotics long-term can increase the likelihood that bacteria become resistant, and the antibiotics stop being effective. These bacterial infections can be dangerous and difficult to treat.

Methenamine is an antiseptic, which stops the growth of bacteria. Previous evidence suggests that it may prevent recurrent urinary tract infections, but it was not conclusive.

To address this gap in the evidence, this study compared methenamine with daily, low-dose antibiotics in women with recurrent urinary tract infections. It found no meaningful difference. Both treatments reduced the number of urinary tract infections, with side effects that were mostly mild.

The researchers say methenamine could be an alternative to antibiotics for preventing frequent urinary tract infections, thereby reducing the use of antibiotics. Further research is needed to explore the long-term safety of methenamine.

For more information about urinary tract infections, visit the NHS website.

Alternatives to antibiotics are needed

Urinary tract infections affect the organs involved in peeing, including the bladder, urethra (the tube that transports urine out of the body), and kidneys. These infections affect as many as 1 in 2 women; they are more common in women than men. About 1 in 4 women who have a first urinary tract infection will go on to have them frequently.

Guidelines from the UK, Europe and US, recommend daily, low-dose antibiotics to prevent urinary tract infections among women who experience them frequently. However, long-term antibiotics can become ineffective at killing bacteria (antibiotic resistance). The UK Government aims to reduce the use of antibiotics. In their 5-year action plan for antimicrobial resistance, they state, “we are heading rapidly towards a world in which our antibiotics no longer work.”

Alternatives to antibiotics are needed, especially where people need to take antibiotics long-term. There is some evidence that methenamine, an oral antiseptic, may prevent recurrent urinary tract infections. To confirm this, researchers compared methenamine with standard low-dose antibiotics for the prevention of recurrent urinary tract infections.

What’s new?

The study included women in the UK who had recurrent urinary tract infections (defined as 2 infections in 6 months, or 3 in a year). Most had experienced 4 or more urinary tract infections in the year before the study. Women who had underlying conditions that increase urinary tract infections (such as impaired bladder control due to injury or disease of the nervous system) were excluded from the study.

The women were treated for 12 months. Half (103) took methenamine twice daily. The other half (102) took 1 of 3 commonly-used antibiotics once daily (nitrofurantoin, trimethoprim or cefalexin). Every 3 months, researchers asked women about any urinary tract infections they had experienced. Symptoms from a predefined list (that needed a short course of antibiotics) were counted as infections.

The researchers found:

  • after 12 months, both treatments similarly reduced urinary tract infections; on average, women in the methenamine group reported marginally more urinary tract infections (1.4) than those in the antibiotic group (0.9)
  • the safety profile of the two treatments was similar, and most side effects were mild.

The researchers also assessed traditional laboratory tests for bacteria in urine. They found that these tests would have missed almost half (48%) of the self-reported, urinary tract infections which were treated with short-course antibiotics.

In the 6 months after treatment stopped, women had few urinary tract infections. However, women in the methenamine group took more short-course antibiotics for these infections (14 days on average) than women in the antibiotic group (8 days).

Women in both groups were highly satisfied with their treatment but found taking antibiotics more convenient.

An economic analysis found that methenamine was, on average, less costly and more effective than antibiotics in the 18 months of the study. Over a women’s lifetime, antibiotics became less costly and more effective than methenamine, but this finding was uncertain.

Why is this important?

The study concludes that methenamine could be an alternative to antibiotics for the prevention of recurrent urinary tract infections. There were slightly more urinary tract infections in the methenamine group, but a patient group did not consider the difference meaningful as it was much less than one infection per year. Women’s satisfaction with treatment was similar in both groups.

Many women (44%) in the methenamine group had no antibiotics during the 12-month treatment period. The researchers say this is encouraging because it shows that methenamine can prevent recurrent infections and reduce antibiotic use.

Researchers took swabs to check for antibiotic-resistant bacteria. During the treatment period, more women in the antibiotic group tested positive for bacteria that were resistant to one or more antibiotics. But in the 6 months after treatment had finished, more women in the methenamine group tested positive for resistant bacteria. This unexpected (secondary) finding could be because women on methenamine received more short-course antibiotics after the study finished. More research is needed to determine whether methenamine reduces antibiotic resistance.

What’s next?

These results led to an ongoing review by the National Institute for Health and Care Excellence (NICE) on whether methenamine can be offered to women with recurrent urinary tract infections. The researchers say that guidelines, such as European Association of Urology Urological Infections Guidelines, could be updated to include methenamine as an option for preventing recurrent infections. This study, along with the NICE review, will allow clinicians and patients to make shared decisions and consider using methenamine rather than antibiotics.

Antibiotic-resistant bacteria are particularly dangerous for some groups, such as elderly people. The researchers say that older women with recurrent urinary tract infections might therefore benefit more than others from methenamine. However, the study was not set up to determine which groups might benefit most from methenamine or which antibiotics were most effective.

Further research could therefore explore the use of methenamine in specific groups, such as in elderly people, or those who need preventive treatment ahead of surgery. It could also assess the long-term safety of methenamine.

Testing urine samples for bacteria would have missed almost half of the urinary tract infections women reported in this study. In clinical practice, recurrent urinary tract infections are often treated without confirming the presence of bacteria. The researchers hope that self-reported infections will be used in future studies, since this method reflects clinical practice.

You may be interested to read

This summary is based on: Harding C, and others. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial. BMJ. 2022;376:e068229.

Another study supporting the use of methenamine for recurrent urinary tract infections: Bortos C, and others. Methenamine hippurate compared with trimethoprim for the prevention of recurrent urinary tract infections: a randomized clinical trial. International Urogynecology Journal. 2022;33: 571–580.

The cost-effectiveness study: King W, and others. Cost-effectiveness of methenamine hippurate compared with antibiotic prophylaxis for the management of recurrent urinary tract infections in secondary care: a multicentre, open-label, randomised, non-inferiority trial. BMJ Open. 2024;14:e074445. 

NIHR Evidence Alert: Do women know how to take a urine sample?

Funding: The study was funded by the NIHR Health Technology Assessment Programme.

Conflicts of Interest: The study authors declare no conflicts of interest.

Disclaimer: Summaries on NIHR Evidence are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that the views expressed are those of the author(s) and reviewer(s) at the time of publication. They do not necessarily reflect the views of the NHS, the NIHR or the Department of Health and Social Care.

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