The Effect of Methenamine Hippurate to Reduce Antibiotic Prescribing in Elderly Women With Recurrent UTI

Summary

Recurrent urinary tract infection (UTI) in elderly women is a major driver of antibiotic prescription. Hence, the question of feasible and appropriate preventive measures are important issues in this field. Methenamine hippurate is frequently prescribed in Norway and Sweden as prophylaxis for recurrent UTI. Methenamine hippurate acts via the production of formaldehyde from hexamine, which in turn acts as a bacteriostatic agent, therefore methenamine hippurate is not defined as an antibiotic. According to a Cochrane review 2012 the rates of adverse events for preventing UTI was low. Although this review showed methenamine hippurate might be effective in preventing UTI in the short term, there is a need for large well-conducted randomised controlled trial (RCT) to clarify both the safety and effectivity of preventive methenamine hippurate for longer term use. This is particularly important for longer term use for people without neuropathic bladder disorders. A Norwegian longitudinal observational study including women aged 50-80 years with recurrent UTI indicated a significant and large reduction of more than 50% in antibiotic prescriptions for UTI after start of prophylactic methenamine hippurate. This further strengthens the need for an RCT of methenamine hippurate as prophylaxis for recurrent UTI.

Timeline

Start

2019-11-01

Primary completion

2023-06-30

Completion

2023-06-30

Publications

• Results Lee BS, Bhuta T, Simpson JM, Craig JC. Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev. 2012 Oct 17;10(10):CD003265. doi: 10.1002/14651858.CD003265.pub3.
• Results Davis C, Rantell A. Lower urinary tract infections in women. Br J Nurs. 2017 May 11;26(9):S12-S19. doi: 10.12968/bjon.2017.26.9.S12.
• Results Barclay J, Veeratterapillay R, Harding C. Non-antibiotic options for recurrent urinary tract infections in women. BMJ. 2017 Nov 23;359:j5193. doi: 10.1136/bmj.j5193. No abstract available.
• Results Aydin A, Ahmed K, Zaman I, Khan MS, Dasgupta P. Recurrent urinary tract infections in women. Int Urogynecol J. 2015 Jun;26(6):795-804. doi: 10.1007/s00192-014-2569-5. Epub 2014 Nov 20.
• Results van Buul LW, van der Steen JT, Veenhuizen RB, Achterberg WP, Schellevis FG, Essink RT, van Benthem BH, Natsch S, Hertogh CM. Antibiotic use and resistance in long term care facilities. J Am Med Dir Assoc. 2012 Jul;13(6):568.e1-13. doi: 10.1016/j.jamda.2012.04.004. Epub 2012 May 9.
• Results Sundvall PD, Stuart B, Davis M, Roderick P, Moore M. Antibiotic use in the care home setting: a retrospective cohort study analysing routine data. BMC Geriatr. 2015 Jun 25;15:71. doi: 10.1186/s12877-015-0073-5.
• Results Cronberg S, Welin CO, Henriksson L, Hellsten S, Persson KM, Stenberg P. Prevention of recurrent acute cystitis by methenamine hippurate: double blind controlled crossover long term study. Br Med J (Clin Res Ed). 1987 Jun 13;294(6586):1507-8. doi: 10.1136/bmj.294.6586.1507.
• Results Brumfitt W, Hamilton-Miller JM, Gargan RA, Cooper J, Smith GW. Long-term prophylaxis of urinary infections in women: comparative trial of trimethoprim, methenamine hippurate and topical povidone-iodine. J Urol. 1983 Dec;130(6):1110-4. doi: 10.1016/s0022-5347(17)51709-7.
• Results Alberg T, Holen O, Blix HS, Lindbaek M, Bentele H, Eriksen HM. Antibiotic use and infections in nursing homes. Tidsskr Nor Laegeforen. 2017 Mar 7;137(5):357-361. doi: 10.4045/tidsskr.16.0621. eCollection 2017 Mar. English, Norwegian.
• Heltveit-Olsen SR, Arnljots ES, Sundvall PD, Gunnarsson R, Kowalczyk A, Godycki-Cwirko M, Platteel TN, Groen WG, Lithen SS, Sundvall S, Ahren C, Grude N, Verheij TJM, Hertogh CMPM, Lindbaek M, Hoye S. Methenamine hippurate as prophylaxis for recurrent urinary tract infections in older women-a triple-blind, randomised, placebo-controlled, phase IV trial (ImpresU). Clin Microbiol Infect. 2025 Nov;31(11):1873-1879. doi: 10.1016/j.cmi.2025.07.006. Epub 2025 Jul 14.
• Heltveit-Olsen SR, Sundvall PD, Gunnarsson R, Snaebjornsson Arnljots E, Kowalczyk A, Godycki-Cwirko M, Platteel TN, Koning HAM, Groen WG, Ahren C, Grude N, Verheij TJM, Hertogh CMPM, Lindbaek M, Hoye S. Methenamine hippurate to prevent recurrent urinary tract infections in older women: protocol for a randomised, placebo-controlled trial (ImpresU). BMJ Open. 2022 Nov 1;12(11):e065217. doi: 10.1136/bmjopen-2022-065217.

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