Methenamine After 70: What the ImpresU Trial Found During Treatment and After Stopping

When discussing a preventive medicine, ask two questions together: what improvement would justify continuing, and what should happen if the medicine is stopped? The ImpresU study makes the second question especially relevant for older women considering methenamine hippurate.

The treatment and follow-up results went in different directions

ImpresU enrolled 289 women aged 70 or older in four European countries; 281 entered its main analysis. Participants received methenamine hippurate 1 g twice daily or placebo for six months, followed by six months off study medication. Most lived at home.¹

During treatment, the rate of antibiotic-treated UTI episodes was lower with methenamine: rate ratio 0.75, 95% confidence interval 0.57–1.00, P = 0.049. That estimates a 25% relative reduction in treatment episodes, not a 25% chance of being cured. The analysis using complete records without imputation was less conclusive (P = 0.078).¹

After treatment stopped, the previous methenamine group had a higher rate of antibiotic-treated episodes: ratio 1.7, confidence interval 1.3–2.3. This finding does not establish the mechanism or an ideal duration. The trial did not compare stopping with continuing methenamine indefinitely.¹

The outcome was antibiotic treatment, not a culture-confirmed count

A 2026 microbiology report from the same trial² helps explain this distinction. Baseline urine was collected while participants had no symptoms. Twenty-nine percent had a dominant urinary bacterium at a concentration of at least 100,000 colony-forming units per millilitre. This was a single sample, rather than repeated sampling to establish persistent asymptomatic bacteriuria.²

Only about half of acute episodes had culture results available, because testing followed local clinical practice. The treatment-episode outcome therefore should not be described as a count of laboratory-confirmed infections.²

The report found no significant difference in E. coli antibiotic-resistance rates between the methenamine and placebo groups. The trial was not powered to establish that difference, so this does not prove resistance can never change. It is also an analysis of the same participants, rather than a second prevention trial.²

A review at six months is not an automatic stopping instruction

NICE, in UK guidance, recommends reviewing methenamine within six months and then every 12 months, or earlier if agreed. Review means checking whether treatment remains appropriate; it does not require everyone to stop at the six-month mark.³

NICE considers it an alternative to daily antibiotic prevention for eligible, nonpregnant women after any current UTI has been adequately treated and earlier appropriate options have not helped enough. It calls for specialist advice for recurrent upper UTIs or complicated lower UTIs.³

For the different question of how methenamine compares with daily antibiotics, see our article about the ALTAR trial and prevention options.

Bring symptom-relief sachets and other medicines to the review

NICE warns against UTI-relief sachets containing potassium citrate or sodium citrate while taking methenamine. They make urine more alkaline and can reduce its effectiveness. Bring the packaging instead of relying on a product’s brand name.³

The US prescribing information lists contraindications including renal insufficiency, severe hepatic insufficiency and severe dehydration. It also says methenamine should not be given with sulfonamides. Ask the prescriber or pharmacist to check kidney and liver history and the complete medication list, including any newly prescribed antibiotic.⁴

The label describes prevention or suppression of frequently recurring infections after an existing infection has been treated with an appropriate antimicrobial. A preventive prescription does not remove the need to assess new urinary symptoms.⁴

Agree on the response to a suspected new UTI

UK NHS⁵ guidance advises urgent GP assessment or NHS 111 for a suspected UTI in someone aged 65 or older. Shivering, a high or low temperature, or pain in the back beneath the ribs also require urgent help.⁵

For suspected UTI with new confusion, drowsiness or difficulty speaking, the NHS⁵ advises emergency care. Outside the UK, use your local urgent or emergency service. Do not assume that taking prevention tablets rules out an infection or explains a sudden change.⁵

At the review appointment, ask who to contact for new symptoms, when a urine sample is wanted and how any treatment pause would be monitored. Write down which medicines to keep taking and who will check possible interactions if an antibiotic is added.

Put the stopping question on the appointment card

The “What to Say in the Room” section in Laugh, Sneeze, Jump includes questions about an option’s intended benefit, review timing, risks and what happens if it is stopped. It also recommends bringing the medicines you buy without a prescription.

For this discussion, add the dates and symptoms of episodes treated as UTIs, antibiotic names, any culture reports and the date prevention began. Ask the clinician to explain the plan for continuing, changing or stopping treatment, with a review date you can put in your calendar.