Aim
To test and compare the effectiveness of methenamine hippurate for the prevention of recurrent urinary tract infections with the current standard daily low-dose antibiotic prophylaxis.
Design
Multicenter, open-label, randomized, non-inferiority trial.
Location in eight centers in the UK, recruiting from June 2016 to June 2018.
Participants
Women ≥18 years of age with recurrent urinary tract infections requiring prophylactic treatment.
Interventions
Random assignment (1:1, using permuted blocks of variable length via a web-based system) to receive antibiotic prophylaxis or methenamine hippurate for 12 months. Treatment allocation was not concealed and crossover between arms was permitted.
Main outcome measure
Absolute difference in the incidence of symptomatic urinary tract infections treated with antibiotics during treatment.
A patient and public participation group predefined the noninferiority margin as one episode of urinary tract infection per person per year. Analyzes conducted in a modified intention-to-treat population included all participants observed for at least six months.
Results
Participants were randomly assigned to antibiotic prophylaxis (n=120) or methenamine hippurate (n=120). The modified intention-to-treat analysis included 205 (85%) participants (antibiotics, n = 102 (85%); methenamine hippurate, n = 103 (86%)).
The incidence of urinary tract infections treated with antibiotics during the 12-month treatment period was 0.89 episodes per person-year (95% confidence interval, 0.65 to 1.12) in the antibiotic and antimicrobial groups. 1.38 (1.05 to 1.72) in the methenamine hippurate group, with an absolute difference of 0.49 (90% confidence interval: 0.15 to 0.84) confirming non-inferiority. 34/142 (24%) in the antibiotic group and 35/127 (28%) in the methenamine group reported adverse reactions and most reactions were mild.
Conclusion In the ALTAR trial, we have demonstrated high levels of efficacy of methenamine hippurate in terms of UTI prevention, and have shown that this efficacy is comparable to prophylaxis recommended by current guidelines (i.e., long-term treatment with low-dose antibiotics). . |
What is already known about this topic?
Long-term daily low-dose antibiotic treatment is the current standard of care for prophylaxis in women with recurrent urinary tract infection and is recommended by national and international guidelines.
Despite the reported success of prophylactic antibiotics, antimicrobial resistance has been directly linked to antibiotic consumption; Consequently, the importance of research into non-antibiotic alternatives has been highlighted.
Systematic reviews have concluded that the non-antibiotic option methenamine hippurate could be effective in preventing urinary tract infections, but noted the need for more large, well-conducted randomized trials.
What this study adds
The ALTAR randomized trial compared the use of methenamine hippurate with low-dose antibiotics in a predefined cohort of women with recurrent urinary tract infection presenting to secondary care
The efficacy of both treatments in the primary and sensitivity analyzes was found to be comparable, suggesting that methenamine hippurate may be appropriate for women with a history of recurrent urinary tract infection.
The range of a priori results reported confirms the clinical utility of methenamine hippurate as a non-antibiotic option for the prevention of urinary tract infection in this pragmatic trial, allowing the results to be generalized.
Discussion
This trial has shown that non-antibiotic preventive treatment for UTI (methenamine hippurate) is not inferior to the standard recommended by current guidelines (daily low-dose prophylactic antibiotics).
This trial adds to the evidence base for the use of methenamine hippurate for prophylactic treatment in adult women with recurrent UTI. Although the methenamine hippurate group had a 55% higher rate of UTI episodes than the antibiotic group, the absolute difference was only 0.49 UTI episodes per year, which has limited clinical consequences.
Comment
Methenamine hippurate works to prevent recurrent urinary tract infections
Using a non-antibiotic antiseptic could slow antibiotic resistance.
An American Urological Association guideline allows 1 year of low-dose antibiotics to suppress recurrent urinary tract infections (UTIs) despite concerns about contributing to antibiotic resistance (J Urol 2019;202:282) . The nonantibiotic urinary antiseptic methenamine hippurate (which is hydrolyzed to bactericidal formaldehyde in the distal tubule) could be a useful alternative, but its effectiveness has not been adequately studied.
In a pragmatic noninferiority trial, UK investigators randomly assigned 240 women with recurrent symptomatic UTI (median, 7 episodes in the past year) to receive daily low-dose antibiotic prophylaxis (i.e., nitrofurantoin, trimethoprim, or cephalexin). , at the discretion of the patient and physician) or methenamine hippurate (100 mg twice daily) for 12 months.
Patients could switch between antibiotics or between treatment strategies. Women who experienced UTI symptoms were advised to seek short courses of antibiotics from their regular doctors.
In a modified intention-to-treat analysis, more antibiotic-treated symptomatic UTIs (with or without bacteriologic confirmation) occurred in the methenamine hippurate group than in the antibiotic group (1.38 vs. 0.89 per patient-year). , but the confidence interval around the difference fell within the prespecified noninferiority limit of 1 UTI per person-year. A similar small difference was observed in the first 6 months after the end of treatment.
Methenamine hippurate appears to be a reasonable non-antibiotic alternative for patients with recurrent urinary tract infections.
Few adverse effects have been observed in short-term studies of methenamine hippurate, but its long-term safety has not been fully evaluated.
Non-antibiotic prophylactic treatment with methenamine hippurate may be appropriate for women with a history of recurrent episodes of urinary tract infections, informed by patient preferences and antibiotic stewardship initiatives, given the demonstration of non-inferiority to antibiotic prophylaxis. daily observed in this trial.
Reference : Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomized, non-inferiority trial. Chris Harding, et al. BMJ 2022;376:e068229
