Introduction

Antibiotic resistance is a growing concern that needs to be addressed. Urinary tract infections (UTIs) are one of the common conditions that are treated with antibiotics and are a source of antibiotic overuse. UTIs affect a significant proportion of women and recurrent UTIs affect the social and occupational activities, leading to physicians prescribing antibiotics for managing the unpleasant symptoms. Methenamine hippurate is a bacteriostatic agent which does not cause antibiotic resistance and has a good safety profile. However, there are no studies that have compared the efficacy of methenamine hippurate with antibiotics.  

Aim

To review randomized controlled trials (RCTs) of adult women in the community with a history of recurrent UTIs and who used methenamine hippurate as treatment or prophylaxis.

Method

Study Design

• Systematic review and meta-analysis of RCTs  

Inclusion Criteria

• Studies comprising women aged >18 years with diagnosis of recurrent or confirmed UTIs
• Studies that compared methenamine hippurate with control/no treatment or compared with any antibiotic

Treatment Strategy

• PubMed, EMBASE, Cochrane databases and clinical trial registries were searched to identify the eligible studies
• A forward-backward citation analysis was performed on references of included studies

Endpoints

Primary Endpoint

• UTI manifested by any combination of the following symptoms such as dysuria, nocturia, pyuria, urgency, burning, fever, frequency, suprapubic pain and loin pain

Secondary Endpoints

• Adverse events (AEs)
• Bacteriuria
• Antibiotic use
• Antibiotic resistance

Results

• The systematic review included 6 studies involving 557 participants
• Of the six studies, three compared methenamine hippurate against placebo or control, and three compared methenamine hippurate with antibiotics
• Among the patients who remained asymptomatic, methenamine hippurate showed a non-statistically significant trend of benefit vs antibiotics over 12 months (risk ratio [RR] 0.65)), and vs control over 6 or 12 months (RR 0.56)
• Methenamine hippurate vs antibiotics also demonstrated a non-statistically significant difference for abacteruria (RR 0.80)
• A similar non-statistically significant trend of benefits for methenamine hippurate for the number of UTI or bacteriuric episodes was noted
• There was no statistically significant difference in the number of patients experiencing AEs between methenamine hippurate and any comparator; OR 0.77
• The most common AEs were nausea, headache and abdominal pain
• There was no consistency in the reporting of antibiotic use and antibiotic resistance

Conclusion

• Methenamine hippurate can prevent recurrent urinary tract infections, however, the difference is statistically not significant when compared to other antibiotics
• The safety profile is also comparable to other antibiotics
• However, further research is warranted to assess its efficacy in preventing UTIs and to evaluate if it can be used as an alternative for antibiotic treatment for UTI

Br J Gen Pract. 2021 Jun 24;71(708):e528-e537. Doi: 10.3399/BJGP.2020.0833.