Could an antiseptic drug prevent recurrent urinary tract infection?

Could an antiseptic drug prevent recurrent urinary tract infections?
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New research has discovered that an antiseptic drug could be an effective alternative to antibiotics for recurrent urinary tract infections, helping with the AMR crisis.

Urinary tract infections affect over half of women once in their lifetime and can be caused by pregnancy, a weakened immune system and not drinking enough fluids. A recurrent urinary tract infection is defined by at least three repeated infections per year or two infections in the preceding six months and can occur in around a quarter of women who have one episode.

Current treatment guidelines recommend a daily dose antibiotic as the standard preventive (prophylactic) treatment for recurrent urinary tract infections. However, long term use of antibiotics can result in antibiotic resistance (AMR) consequently. New research into non-antibiotic alternatives must be a priority in the rise of resistance to antibiotics.

Finding effective treatment for recurrent urinary tract infections

The antiseptic drug in question, methenamine hippurate, sterilises urine and stops the growth of certain bacteria; it has been examined in previous studies and has shown positive results in preventing recurrent urinary tract infections.  However, the evidence is inconclusive and further randomised trials are needed.

To assess this finding further, a team of UK researchers driven by clinicians and scientists from Newcastle-upon-Tyne set out to analyse if methenamine hippurate is an effective alternative to standard antibiotic treatment for preventing recurrent urinary tract infections in women.

The research team assembled 240 women aged 18 and over with recurrent urinary tract infections requiring prophylactic antibiotic treatment. On average, the participants experienced over six urinary tract infections 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.

Tackling antibiotic resistance

During the 12-month treatment period, the recurrent urinary tract infection was 0.89 episodes per person per year in the antibiotic group and 1.38 in the methenamine group – an absolute difference of 0.49 episodes per person per year.

This small difference between the two groups was less than the predefined threshold of one urinary tract infection episode per year, suggesting that methenamine was no worse than antibiotics at preventing recurrent urinary tract infections. This finding could transform recurrent urinary tract infections treatment and play a large part in the fight against antibiotic resistance, improving the quality of life of people with recurrent infections. Methenamine also showed similar levels of adverse reactions and treatment satisfaction compared to daily antibiotics.

Furthermore, the results were similar after further analysis, such as excluding days taking antibiotics for urinary tract infection, adding substance to the findings.

However, the researchers noted that there is minimal data on the long-term safety of methenamine hippurate and some trial limitations include lack of blinding and differences in antibiotics prescribed, which may have affected the results. They also noted that four participants allocated to methenamine were admitted to a hospital because of a UTI and six participants reported fever during a UTI episode.

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.

“Although the results need cautious interpretation, they align with others, and this new research increases the confidence with which methenamine hippurate can be offered as an option to women needing prophylaxis against recurrent urinary tract infection,” said Australian researchers in a linked editorial.

The appropriateness of the non-inferiority margin (one episode of urinary tract infection) used in this trial to capture clinically meaningful differences between treatments will likely inspire debate, they added.

However, they agreed that decisions on preventive treatment for recurrent urinary tract infection are well suited to shared decision making between each patient and their doctor, and say this trial “will help to inform this important conversation.”


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