Methenamine hippurate prevents recurrent UTI in women

Nonantibiotic treatment with methenamine hippurate shows high levels of efficacy in women with a history of recurrent episodes of urinary tract infection (UTI), which is comparable to the current guideline-recommended prophylaxes (ie, long-course, low-dose antibiotics), according to a study.

“The increased rates of antimicrobial resistance development associated with the antibiotic arm as shown in the primary uropathogen Escherichia coli might encourage patients and clinicians to consider methenamine hippurate as a first line treatment for UTI prevention in women,” the researchers said.

This multicentre, open-label, randomized, noninferiority trial was conducted across eight centres in the UK, recruiting women aged ≥18 years with recurrent UTI and requiring prophylactic treatment from June 2016 to June 2018. Participants were randomly assigned to receive either antibiotic prophylaxis (n=120) or methenamine hippurate (n=120).

The researchers calculated the absolute difference in incidence of symptomatic, antibiotic-treated UTI during treatment. The noninferiority margin was predefined as one episode of UTI per person-year by a patient and public involvement group. Finally, analyses were carried out in a modified intention-to-treat (mITT) population observed for at least 6 months.

Of the participants, 205 (85 percent) were included in the mITT analysis (antibiotics, n=102, 85 percent; methenamine hippurate, n=103, 86 percent). [BMJ 2022;376:e068229]

Over 12 months of treatment, the incidence of antibiotic-treated UTI reached 0.89 episodes per person-year (95 percent confidence interval [CI], 0.65‒1.12) in the antibiotic group and 1.38 (95 percent CI, 1.05‒1.72) in the methenamine hippurate group, with an absolute difference of 0.49 (90 percent CI, 0.15‒0.84) that confirmed noninferiority.

Additionally, adverse reactions were mostly mild, occurring in 34 of 142 (24 percent) women in the antibiotic group and 35 of 127 (28 percent) in the methenamine group.

Antibiotic resistance

A recent study reported a higher risk of developing antibiotic resistance among older patients receiving such treatment, as well as an increased risk of antibiotic-related complications, such as Clostridium difficile infection. The authors concluded that such risks outweighed the benefits on long-term antibiotic prophylaxis in older UTI patients. [Clin Infect Dis 2021;73:e782-791]

Findings of the current study “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 researchers said.

Moreover, UTI reductions during the treatment period were consistent with previously published results from systematic reviews and were similar in both arms, which confirmed efficacy for both treatments. [Cochrane Database Syst Rev 2004;2004:CD001209; Cochrane Database Syst Rev 2012;10:CD003265]

The present study was limited by its lack of blinding, the heterogeneity of prophylactic antibiotics prescribed, the scarcity in data regarding long-term safety of methenamine hippurate, and the exclusion of the added value of urinary acidification in the analysis.

“Further research should focus on the use of methenamine hippurate as a preventive treatment for recurrent UTI in more narrowly defined patient groups,” the researchers said. “Increased adoption of this treatment as prophylaxis against recurrent UTI will allow for the generation of long-term safety data now that efficacy has been demonstrated in our study.”