Introduction

The risk of recurrent urinary tract infections (UTIs) is higher in older, postmenopausal women. Repeated exposures to urinary antibiotics select for AMR pathogens. There is a need to explore and implement effective non-antibiotic prophylactic treatments for recurrent UTIs. The ALTAR trial has demonstrated non-inferiority of methenamine hippurate to low-dose prophylactic antibiotics in women aged about 50 years. This preventive urinary antiseptic drug has been associated with mild side effects and beneficial preventive effect on women with recurrent UTIs. However, the data on efficacy of methenamine hippurate in older women is limited.

Aim

To assess the preventive effect of methenamine hippurate on recurrent UTIs in older women.

Method

Study Design

Treatment Strategy 

• Women ≥70 years with rUTIs defined as >2 antibiotic courses for UTIs during the last 6 months or >3 antibiotic courses for UTIs during the last 12 months were recruited from general practice
• The participants were randomised to receive either methenamine hippurate 1g × 2 or placebo 1 tablet × 2 daily for 6 months, followed by a drug-free period of 6 months
• The follow up was taken monthly on telephone during the treatment period (day 30-150), at the end of treatment period (day 180) and at the end of study (day 360)

Endpoints

Primary Endpoint

Secondary Endpoints

• Number of antibiotic treatments for UTIs during the follow-up period
• UTI symptom severity
• Duration of episode

Safety Endpoint

Results

• Out of the 289 recruited women, 281 (97%) were included in the modified intention-to-treat analysis (mITT)
• The methenamine hippurate and placebo groups comprised 140 and 141 women respectively
• During the treatment period, the incidence of antibiotic treatments for UTIs were lower in the methenamine hippurate group vs placebo group, with an incidence rate ratio of 0.75 (p=0.049)
• However, in the follow-up period, the incidence of antibiotic treatments for UTIs was higher in the treatment group, with an incidence rate ratio of 1.7 (p<0.001)
• There were no significant differences in UTI symptom severity or duration of the episode between the groups
• The rate of complications was comparable; 43% in treatment group vs 55% in placebo group, with the serious adverse events equally distributed among the groups

Conclusion

• Methenamine hippurate reduces the frequency of recurrent urinary tract infections in older women by about 25%, offering an alternative to low-dose antibiotic prophylaxis with minimal side effects and low risk of antimicrobial resistance
• However, stopping treatment after six months may increase the risk of UTI relapse risk, so clinicians should plan initiation and discontinuation carefully

Clin Microbiol Infect. 2025 Nov;31(11):1873-1879.