Introduction

Recurrent urinary tract infections (rUTIs) in women are common and challenging to manage, affecting quality of life and increasing healthcare burden. Rising antimicrobial resistance (AMR) poses global threats, significantly increasing the mortality and healthcare costs. Current guidelines recommend antibiotics for the prevention and treatment of rUTIs. Non-antibiotic measures include estrogen replacement therapy in postmenopausal women. There is no strong clinical evidence on the use of other non-antibiotic options like cranberry and probiotics. Methenamine hippurate, a urinary antiseptic since 1894, is regaining interest as an alternative to antibiotics, supported by recent trials. It works by releasing formaldehyde in acidic urine, is effective against common pathogens, and has a favorable safety profile.

Aim

To assess the efficacy of methenamine hippurate in the prevention and treatment of recurrent UTIs in adult women.

Method

Study Design

Study Inclusion Criteria 

• Studies that included adult women with recurrent UTIs
• Intervention was oral methenamine hippurate versus placebo or antibiotics
• Only English-language RCTs with methenamine treatment arms

Search Strategy, Data Extraction and Analysis 

• A comprehensive literature search was conducted across major databases and urological journals to identify studies on oral methenamine hippurate for preventing recurrent UTIs in women
• Search was done following the Cochrane and PRISMA guidelines
• Eligible studies were screened, and data on design, treatment, and outcomes were extracted
• Due to heterogeneity, results were narratively presented

Results

• This systematic review analysed six randomized controlled trials involving 741 women; 322 women received methenamine hippurate and 419 received antibiotics
• Five trials compared methenamine with antibiotics (trimethoprim, nitrofurantoin, cefalexin) or antiseptic washes; one used placebo
• Methenamine doses ranged from 1–2 g daily for 6–12 months, with follow-up lasting 12–24 months
• The analysis revealed that methenamine was effective in extending the mean period between symptomatic episodes of UTIs, leading to the patients being free of symptoms and infections
• Methenamine hippurate was also associated with reduction in the number of UTI episodes
• Breakthrough infections were common, predominantly E. coli
• Antibiotic resistance was higher in antibiotic groups, though ALTAR reported multidrug-resistant E. coli in methenamine users at 18 months
• Side effects and dropout rates varied across trials
• Methenamine generally caused mild gastrointestinal issues and had comparable dropout rates to antibiotics
• Results were heterogeneous, limiting pooled analysis

Conclusion

• Methenamine hippurate showed comparable efficacy to antibiotic prophylaxis for recurrent UTIs.
• Methenamine hippurate may represent a promising non-antibiotic alternative for women seeking long-term prophylaxis against recurrent infections.

Curr Opin Urol. 2023 Nov 1;33(6):488-496. Doi: 10.1097/MOU.0000000000001108.