The current guidelines as the standard preventive (prophylactic) treatment for recurrent urinary tract infection (UTI) recommend daily low dose antibiotics.

However, such long term use of antibiotics has been linked to antibiotic resistance, so research into non-antibiotic alternatives is urgently needed. Methenamine hippurate is a drug that sterilises urine, stopping the growth of certain bacteria. Previous studies have shown that it could be effective in preventing UTIs, but the evidence is inconclusive and further randomised trials are needed.

A team of UK researchers, led by clinicians and scientists from Newcastle-upon-Tyne, set out to test if methenamine hippurate is an effective alternative to standard antibiotic treatment for preventing recurrent UTI in women. The findings of the study were published in the journal The BMJ.

Their findings are based on 240 women (aged 18 or over) with recurrent urinary tract infections requiring prophylactic treatment. On average before trial entry, these women experienced over six UTI episodes per year.

Women were recruited from UK secondary care centres between June 2016 and June 2018 and were randomly assigned to daily antibiotics (102 women) or daily methenamine hippurate (103 women) for 12 months, with three monthly assessments up to 18 months.

The non-inferiority margin, defined after a series of patient focus group meetings, was a difference of one UTI episode per year. During the 12 month treatment period, the UTI rate was 0.89 episodes per person-year in the antibiotic group and 1.38 in the methenamine group - an absolute difference of 0.49 episodes per person-year.

This small difference between the two groups was less than the predefined threshold of one UTI episode per year, suggesting that methenamine was no worse than antibiotics at preventing urinary tract infection. Methenamine was also associated with reduced antibiotic consumption and similar levels of adverse reactions and treatment satisfaction compared to daily antibiotics.

And results were similar after further analyses, such as excluding days taking antibiotics for urinary tract infection, adding weight to the findings. The researchers point out that data regarding the long term safety of methenamine hippurate are scarce, and they acknowledge some trial limitations, including lack of blinding and differences in antibiotics prescribed, that may have affected their results.

They also note that four participants allocated to methenamine hippurate were admitted to the hospital because of UTI, and six participants who were allocated to methenamine hippurate reported fever during a UTI episode (febrile UTI). However, they say this was a well-designed trial that accurately represented the broad range of women with recurrent UTI seen regularly in routine NHS practice.

As such, they said their results "could support a change in practice in terms of preventive treatments for recurrent UTI and provide patients and clinicians with a credible alternative to daily antibiotics, giving them the confidence to pursue strategies that avoid long term antibiotic use."

The information provided by this trial "might encourage patients and clinicians to consider methenamine hippurate as a first-line treatment for UTI prevention in women," they added.