"This trial should certainly be looked at by guideline writers and policy makers alike and may alter current recommendations," Dr. Chris Harding of Freeman Hospital/Newcastle upon Tyne, UK, told Reuters Health by email. "The study demonstrates equivalent efficacy in terms of UTI prevention when methenamine is compared to the current guideline-recommended standard treatment of daily low-dose preventative antibiotics in a well-defined population of women suffering recurrent UTI episodes."
"Previous work has suggested that methenamine may be useful, but this trial provides further high-quality evidence and quantification of efficacy," he said. "The pragmatic methodology allows generalizability of results, as the population studied represents the patients we all see in our daily practice."
To boost generalizability, he added, the team used wide inclusion criteria for trial entry and relied less on urine culture results and more on clinical evaluation.
As reported in The BMJ, Dr. Harding and colleagues at eight UK centers studied 205 women (mean age, 50) with a median six UTIs in the year before entry. Participants were randomly assigned to receive antibiotic prophylaxis or methenamine hippurate for 12 months.
For antibiotic prophylaxis, patients received either once-daily oral nitrofurantoin (50 mg or 100 mg), trimethoprim (100 mg), or cefalexin (250 mg), depending on previous urine culture results and individual history of allergy or intolerance.
Methenamine hippurate was prescribed as a twice daily 1 g oral dose.
A patient and public involvement group helped define the main outcome measure; the group stressed the importance of a practical UTI definition rather than sole reliance on microbiological tests. As a result, the main outcome was the absolute difference in incidence of symptomatic, antibiotic-treated UTIs during the study period. The predefined non-inferiority margin was one episode of UTI per person year.
The incidence of antibiotic-treated UTIs was 0.89 episodes per person year in the antibiotics group and 1.38 in the methenamine hippurate group, with an absolute difference of 0.49 that confirmed non-inferiority.
Adverse reactions were reported by 24% of the antibiotic group and 28% of the methenamine group and most reactions were mild. Two serious adverse reactions (severe abdominal pain and elevated alanine transaminase) were reported in the antibiotic group.
In a six-month post-treatment follow-up, the UTI incidence rate was 1.19 episodes per person year in the antibiotic prophylaxis group and 1.72 in the methenamine hippurate groups (absolute difference, 0.53).
Four participants in the methenamine hippurate group were admitted to hospital because of UTI, and six reported a fever during a UTI episode (febrile UTI).
Nonetheless, Dr. Harding said, "Our results could support a change in practice in terms of preventive treatments for recurrent UTI and provide patients and clinicians with a credible alternative to daily antibiotics, giving them the confidence to pursue strategies that avoid long term antibiotic use."
"The information will allow clinicians and patients to undertake a shared decision-making process relating to UTI preventive treatments," he said. "The study showed a small numerical difference in UTI incidence between the daily antibiotics and methenamine hippurate groups, but the potential trade-off includes the avoidance of antibiotic consumption, which is closely associated with antimicrobial resistance development."
Dr. Mina Bakhit of Bond University, Gold Coast in Australia, coauthor of a related editorial, commented in an email to Reuters Health, "Results from this study would help clinicians to be more confident in recommending methenamine hippurate as an alternative to antibiotic treatment, especially to help minimize the global threat of antibiotic resistance."
However, like Dr. Harding, he said, "Decisions on preventative treatment for recurrent UTI would need to be discussed with the patient. The benefits and harms for both options need to be presented clearly and each patient's values and preferences need to be considered."
"Further synthesized evidence of harms of antibiotics commonly prescribed to prevent recurrent UTI is needed, including antibiotic resistance," he noted, as well as long-term safety data on methenamine hippurate.
SOURCE: https://bit.ly/3tYTrlo and https://bit.ly/3MWy6l5 The BMJ, online March 9, 2022.
By Marilynn Larkin
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