Methenamine Hippurate Reduces Recurrent UTIs but Relapse Increases After Discontinuation: ImpresU Trial
Norway: Older postmenopausal women face a heightened risk of recurrent urinary tract infections (UTIs), often leading to repeated antibiotic use and rising concerns about antimicrobial resistance. A new study suggests that methenamine hippurate, a non-antibiotic urinary antiseptic, may offer a preventive alternative—though its benefits may depend on continued use.
Published in Clinical Microbiology and Infection, the phase IV ImpresU trial was led by Silje Rebekka Heltveit-Olsen from the University of Oslo and collaborators across Europe. The study explored the effectiveness of methenamine hippurate in preventing recurrent UTIs in women aged 70 years and older, a group for whom evidence has been limited despite promising results in younger populations.
The investigators conducted a rigorous triple-blind, randomized, placebo-controlled trial across general practice settings in Norway, Sweden, Poland, and the Netherlands. Recruitment began in December 2019, with follow-up completed by June 2023. Participants with a history of recurrent UTIs were randomly assigned to receive either methenamine hippurate (1 g twice daily) or a matching placebo for six months, followed by an additional six-month observation period.
A total of 289 women were enrolled, of whom 281 were included in the final analysis.
The trial revealed the following findings:
- During the six-month treatment period, women receiving methenamine hippurate required fewer antibiotic courses for UTIs compared to the placebo group.
- Methenamine hippurate use was associated with an approximate 25% reduction in antibiotic-treated UTI episodes, which was statistically significant.
- After discontinuation, the trend reversed, with a higher rate of antibiotic-treated UTIs observed in the methenamine hippurate group during the six-month follow-up period.
- The findings indicate that the preventive benefit may not persist after stopping treatment, with a potential increase in relapse risk.
- No significant differences were observed between the groups in terms of UTI symptom severity or duration.
- Complication rates were similar in both groups.
- Methenamine hippurate was well tolerated, showing a safety profile comparable to placebo.
The findings align with earlier research, such as the ALTAR trial, which demonstrated that methenamine hippurate could be as effective as low-dose antibiotics in preventing UTIs in younger women. The current study extends this evidence to older women, highlighting its potential as a strategy to reduce antibiotic exposure and limit the development of resistant pathogens.
The researchers noted that while methenamine hippurate shows promise as a preventive option with minimal side effects and low risk of promoting antimicrobial resistance, clinicians should be cautious about stopping therapy, given the observed increase in infection rates after discontinuation.
Overall, the study highlights the need for individualized treatment strategies in older women with recurrent UTIs and supports the consideration of methenamine hippurate as a non-antibiotic prophylactic option, particularly in the context of growing antimicrobial resistance concerns.
Reference:
Heltveit-Olsen SR, Arnljots ES, Sundvall PD, Gunnarsson R, Kowalczyk A, Godycki-Cwirko M, Platteel TN, Groen WG, Lithén SS, Sundvall S, Åhrén C, Grude N, Verheij TJM, Hertogh CMPM, Lindbæk M, Høye S. Methenamine hippurate as prophylaxis for recurrent urinary tract infections in older women-a triple-blind, randomised, placebo-controlled, phase IV trial (ImpresU). Clin Microbiol Infect. 2025 Nov;31(11):1873-1879. doi: 10.1016/j.cmi.2025.07.006. Epub 2025 Jul 14. PMID: 40669691.
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