Methenamine hippurate and equivalent prophylactic antibiotics for women with recurrent UTIs

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Methenamine hippurate is equivalent to the use of low dose prophylactic antibiotics for the prevention of recurrent urinary tract infections

Methenamine hippurate (MH) is not inferior to the daily use of low-dose prophylactic antibiotics in the management of women with recurrent UTIs. This was the main finding of an open-label randomized trial conducted by researchers from the Department of Urology at Freeman’s Hospital in Newcastle upon Tyne, UK.

A it is estimated that 40-50% of women suffer from at least one urinary tract infection (UTI) in their lifetime and of these, 20-30% will have a recurrence 3-4 months after their initial infection. A recurrent ITU is defined as two or more infections in six months or three or more in a year and according to UK NICE guidelines, women with a recurrent UTI who are not pregnant should have a trial of antibiotic prophylaxis. However, this recommendation to continue antibiotics long-term contradicts the UK government document, “Combating Antimicrobial Resistance 2019-2024”, one of the main objectives of which was to reduce the need for and inadvertent exposure to antimicrobials.

One method to reduce the need for long-term antimicrobial therapy is the increased use of non-antibiotic alternatives which include drugs such as methenamine hippurate. A Cochrane systematic review examining the value of methenamine hippurate concluded that the may be effective in preventing UTIs in patients, but further large, well-conducted RCTs are needed to clarify this issue..

Trying to answer the above question, the UK team undertook a randomised, open-label, non-inferiority trial to compare the effectiveness of MH, which is a urinary antiseptic, to current standard low-dose antibiotic prophylaxis. , for the prevention of episodic diseases. UTI requiring antibiotic treatment. The patients included were adult women with a recurrent UTI for whom their clinician had decided that antibiotic prophylaxis would be appropriate. Individuals were randomized 1:1 to receive antibiotic prophylaxis (nitrofurantoin, trimethoprim, or cefalexin once daily) or MH at a dose of 1 g twice daily. When an individual has experienced an episode of symptomatic UTI, they have been advised to seek antibiotic treatment through their GP. Patients were followed for a period of 18 months and the primary outcome was the incidence of symptomatic UI episodes treated with antibiotics in the previous 12 months which was self-reported. The authors set a predefined non-inferiority margin of a difference of one UT episode per year between the two therapies.

Methenamine hippurate and episodes of UI

There were 102 women (mean age = 51.1 years) assigned to antibiotic therapy and 103 (same mean age) assigned to HD.

There were 90 episodes of symptomatic UI reported over 101 person-years in those receiving antibiotics and 141 episodes over 102 person-years in the HD group. The incidence of UTIs treated with antibiotics was therefore 0.89 episodes in the antibiotic group and 1.38 in the HD group, giving an absolute difference of 0.49 (95% CI 0.15 – 0 ,84). Since the upper limit of the 95% confidence interval was less than one, the authors concluded that both treatments were non-inferior.

The authors added that the observed absolute difference of 0.49 was of limited clinical significance and concluded that MH appeared to have a high level of efficacy for the prevention of UTIs and suggested that it should be considered by clinicians as a first-line treatment for the prevention of UTIs in women.

Quote
Harding C et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicenter, open, randomized, non-inferiority trial BMJ 2022

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