Methenamine hippurate as good as antibiotic prophylaxis for recurrent UTI

Daily antibiotics are the current guideline-recommended standard for urinary tract infection (UTI). Interestingly, in the randomized, open-label ALTAR trial presented at EAU 2022,  the urinary antiseptic methenamine hippurate was noninferior to antibiotic prophylaxis in women with recurrent UTI.

“I think this trial provides good evidence that methenamine hippurate could be considered as a new standard first-line option for the prevention of UTI in women,’’ said study investigator Christopher Harding of the Freeman Hospital in Newcastle upon Tyne, UK.

Over the course of 12 months, the incidence of UTI treated with antibiotics was 0.89 episodes per person-year and 1.38 episodes in patients treated with methenamine hippurate (absolute difference 0.49 episodes, 90 percent confidence interval  [CI], 0.15–0.84). [BMJ 2022;doi:10.1136/bmj-2021-0068229]

Methenamine hippurate met the study’s noninferiority margin, defined as a difference of one UTI episode per year, Harding continued.

Overall, the use of both prophylactic antibiotics and methenamine hippurate substantially reduced the number of UTIs among the 240 trial participants. In the 12 months prior to the trial entry, women in the antibiotic cohort had an average of 6.8 self-reported UTIs vs 7.0 in the methenamine hippurate cohort.

The modified intention-to-treat (ITT) population included 205 patients with 6 months of follow-up data. Harding reported that the noninferiority margin was not breached in other analyses, which included a complete ITT analysis of the entire study cohort, as well as a per-protocol analysis of patients who had at least 90 percent compliance with their treatment protocols.

In the 6-month post-treatment follow-up period, the UTI incidence rates were 1.19 (95 percent CI, 0.86-1.52) and 1.72 (95 percent CI, 1.27-2.18) episodes per year in the antibiotic prophylaxis and methenamine hippurate groups, respectively.

As for the secondary outcome of antibiotic resistance explored in cultures from both perineal swabs and urine samples, a higher proportion of patients assigned to daily prophylactic antibiotics had resistance to at least one antibiotic in Escherichia coli isolates from perineal swabs, compared with patients assigned to methenamine hippurate.

“At the end of the trial, multidrug resistance was slightly higher in patients on methenamine,” Harding said. There were six cases of febrile UTI in the methenamine group, four of which resulted in hospitalization.

The study recruited women from secondary care urology and urogynaecology centres in the UK. There was a 12-month treatment period followed by a 6-month follow-up period. Recruitment was completed in June 2018 and the final follow-up visit took place in January 2020.

The mean age of the participants was 50 years, the majority of them perimenopausal/postmenopausal who were recommended prophylaxis for UTI by their physicians. Recurrent UTI was defined as at least three episodes of symptomatic UTI in the previous 12 months or at least two episodes in the past 6 months. Treatment choices for antibiotic prophylaxis were nitrofurantoin, trimethoprim, or cefalexin given orally once daily. Methenamine hippurate was given orally twice daily. Patients were allowed to switch between antibiotic drugs or between treatment strategies.

Of patients assigned to antibiotic prophylaxis, 55 percent received nitrofurantoin, 25 percent trimethoprim, and 20 percent cefalexin. Twenty patients (18 percent) allocated to methenamine hippurate switched to antibiotic prophylaxis, while seven (6 percent) switched from antibiotic prophylaxis to methenamine hippurate.

Harding said ALTAR was unique in that it relied on a primary outcome that did not depend on microbiological culture, but rather on symptomatic antibiotic-treated UTI that was self-reported by the participants.  The noninferiority margin was also completely decided by the patients.

“Increased adoption of methenamine hippurate as a prophylaxis against recurrent UTI will allow for the generation of long-term safety data now that efficacy has been demonstrated in our study,” he added.