Methenamine hippurate is a urinary antibacterial agent with a wide spectrum covering both gram-positive and gram-negative organisms. The drug has a dual mechanism of action — the methenamine part is converted to the bactericidal formaldehyde in an acidic environment, in this case urine, while hippuric acid itself has a bacteriostatic effect on urinary tract pathogens.
The ALTAR (alternative to prophylactic antibiotics for the treatment of recurrent UTIs in women) trial was an open-label non-inferiority study involving 240 women with recurrent UTI requiring antibiotic treatment who were randomised to receive antibiotic prophylaxis (n=120) or methenamine hippurate (1g twice daily; n=120) for 12 months with follow-up assessments every three months until month 18.
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 six months. Antibiotic prophylaxis comprised nitrofurantoin 50mg or 100mg (n=66), trimethoprim 100mg (n=30) or cefalexin 250mg (n=24) given once daily, depending on previous urine culture results and individuals' history of allergy or intolerance.
In the modified intent-to-treat population (n=205 [methenamine n=103; antibiotics n=102]), 90 symptomatic, antibiotic treated UTI episodes were reported over 101 years of follow-up in the antibiotic group compared with 141 episodes over 102 years of follow-up in the methenamine group. This equates to 0.89 episodes per person per year (95% CI 0.65-1.12) in the antibiotic group versus 1.38 (95% CI 1.05-1.72) in the methenamine group with an absolute difference of 0.49 (90% CI 0.15-0.84).
The researchers state that with the upper limit of the 90% confidence interval below the non-inferiority limit of one, methenamine hippurate can be considered to be non-inferior to antibiotic prophylaxis in this setting.
The rates of adverse events were low and comparable across all treatment groups.
The researchers conclude that their findings demonstrate that non-antibiotic preventive treatment with methenamine hippurate has comparable efficacy to the current guideline recommended standard (daily, long-course, low-dose antibiotics), adding to the evidence base for its use in women with recurrent UTI.
They add that their findings "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."
Discussing the study findings in a linked editorial, researchers from the Institute for Evidence Based Healthcare at Bond University in Queensland, Australia, state that "although the results need cautious interpretation, they align with others, and this new research increases the confidence with which methenamine hippurate can be offered as an option to women needing prophylaxis against recurrent UTI."