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Methenamine hippurate, a urinary antiseptic, is no less effective than antibiotics when used as a prophylactic treatment for women with recurrent urinary tract infections (UTIs), study results published in the BMJ on 9 March 2022 suggest.
The medicine could therefore be an appropriate non-antibiotic alternative to prophylactic antibiotics, informed by patient preferences and antibiotic stewardship, the authors concluded.
In the randomised, non-inferiority trial, 240 women aged 18 years or over with recurrent UTI were assigned to received either antibiotic prophylaxis — the current standard treatment for recurrent UTI prevention — or methenamine hippurate.
‘Recurrent UTI’ was defined as repeated UTI with a frequency of at least two episodes in the preceding six months, or three episodes in the past year.
Those in the methenamine hippurate group took it twice daily for 12 months, while those in the antibiotic group took either nitrofurantoin, trimethoprim or cefalexin daily for 12 months.
The researchers found that the incidence of UTIs requiring antibiotic treatment during the 12-month treatment period was 0.89 episodes per person per year (95% confidence interval [CI] 0.65–1.12) in the antibiotic groups and 1.38 (1.05–1.72) in the methenamine hippurate group.
This amounted to an absolute difference of 0.49 (90% CI 0.15–0.84), which was less than the non-inferiority margin of one UTI episode per year.
The non-inferiority margin was set after a series of patient focus group meetings and is defined as the threshold, under which the experimental treatment can be considered as non-inferior to the usual treatment.
“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,” the authors wrote.
“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,” they added.
Philip Howard, a member of the Royal Pharmaceutical Society’s Antimicrobial Resistance (AMR) expert advisory group, said that AMR resistance in antibiotics used to treat UTIs in women had been a problem “for some time”, necessitating a switch from trimethoprim to nitrofurantoin “many years ago”.
“Within England, there is no sentinel surveillance of UTI AMR in the community, so we don’t know the true level of AMR in nitrofurantoin, trimethoprim or cefalexin,” he said.
“However, based on samples sent to the laboratory for sensitivity testing, which might overestimate resistance, E.coli AMR to nitrofurantoin is around 2.5%, trimethoprim ~25% and cefalexin ~10%. However, use drives resistance, so any alternatives may help maintain resistance at current rates.”
Howard added that the National Institute for Health and Care Excellence (NICE) recommended alternative strategies for preventing recurrent UTI before continuous daily antibiotics, which need reviewing every six months.
“NICE did review methenamine but did not recommend it because continual antibiotics performed better and caused less harm. This study shows that prophylactic continual antibiotics are still better than methenamine, but that adverse effects are similar in both groups.
“Methenamine is still widely used in England despite not being in the NICE guidelines for recurrent UTI. NICE will no doubt review their guidance in light of the new evidence.”
