Urinary antiseptic noninferior to antibiotics for recurrent UTI prevention in women

The urinary antiseptic methenamine hippurate was noninferior to prophylactic antibiotics in preventing urinary tract infections (UTIs) in women who had them repeatedly, a randomized trial found.

The ALTAR (ALternative To prophylactic Antibiotics for the treatment of Recurrent UTIs in women) trial recruited women ages 18 years and older who had recurrent UTIs and required prophylactic treatment from eight secondary care urology and urogynecology centers in the U.K. from June 2016 to June 2018. Researchers randomly assigned participants to receive daily, low-dose antibiotic prophylaxis (n=120) or methenamine hippurate (n=120) for 12 months. Treatment allocation was not masked, and crossover between arms was permitted. The primary clinical outcome measure was the incidence of symptomatic, antibiotic-treated UTI episodes reported by participants over the treatment period. The noninferiority margin (one episode of UTI per person-year) was predetermined by a patient and public involvement group, which considered that a clinically meaningful difference. Results were published March 9 by The BMJ.

Of the 120 women assigned to antibiotics, 66 (55%) received nitrofurantoin, 30 (25%) received trimethoprim, and 24 (20%) received cefalexin. Twenty-two (18%) participants in the methenamine hippurate group switched to receive antibiotic prophylaxis, and seven (6%) participants in the antibiotics group switched to receive methenamine hippurate. In the modified intention-to-treat population, 90 symptomatic, antibiotic-treated UTI episodes were reported during 101 person-years of follow-up in the antibiotics group versus 141 episodes reported during 102 person-years in the methenamine hippurate group. Incidence of antibiotic-treated UTIs was 0.89 episode per person-year (95% CI, 0.65 to 1.12 episodes per person-year) in the antibiotics group and 1.38 episodes per person-year (95% CI, 1.05 to 1.72 episodes per person-year) in the methenamine hippurate group, with an absolute difference of 0.49 episode per person-year (90% CI, 0.15 to 0.84 episode per person-year) confirming noninferiority. Adverse reactions were reported by 34 of 142 (24%) participants in the antibiotics group and 35 of 127 (28%) participants in the methenamine hippurate group. Most reactions were mild.

Limitations of the trial include its lack of blinding and the heterogeneity of prophylactic antibiotics prescribed, the study authors noted. They added that future research should focus on the use of methenamine hippurate as a preventive treatment for recurrent UTI in more narrowly defined patient groups.

Whether the noninferiority margin used in the trial was of the right magnitude to capture a clinically meaningful difference between treatments is likely to inspire debate, an accompanying editorial noted.

“However, we agree with the authors that decisions on preventive treatment for recurrent urinary tract infection are well suited to shared decision making, where options are presented, the benefits and harms of each option are discussed, and each patient's values and preferences are considered before patients and clinicians decide together on the next steps,” the editorialists wrote.