Recurrent urinary tract infections in women - a major problem | The BMJ

2022-04-19 09:47:10 By : Ms. Tina Zhao

Methenamine hippurate for recurrent urinary tract infections

Harding et al’s study on methenamine hippurate for recurrent urinary tract infections in women is a step forward in recognising that these infections are a major problem which is often overlooked or ignored [1]. Frequent, distressing symptoms were reported by large numbers of women to a Woman’s Hour phone-in programme on the subject. (The condition is also known as the bladder pain syndrome and previously as the urethral syndrome.)

The action of methenamine hippurate depends on the production of formaldehyde [2]. Information about its long-term safety is lacking [3]. Manufacturers advise it is preferable to avoid it in pregnancy [4]. For other women, a non-antibiotic treatment avoids the risk of increasing antibiotic resistance and the side effects of long-term prophylaxis with antibiotics such as trimethoprim, nitrofurantoin or cefalexin.

Methenamine hippurate brands usually contain an ingredient that helps to make the urine acidic [2, 4]. It is under acid conditions that formaldehyde is produced, so it may be useful to check the urine pH in patients who do not respond.

The underlying cause of this syndrome has been investigated by Dr Rosalind Maskell, who reported that the recurrent symptoms are due to antibiotics disturbing the protective commensal flora of the distal third of the urethra (the upper urethra is normally sterile) [5]. She found that antibiotic courses allowed more resistant and fastidious bacteria from the commensal flora (often lactobacilli) to invade the sterile upper areas of the urethra. Progression of the condition sometimes resulted in interstitial cystitis with chronic inflammation of the bladder wall. Dr Maskell recommended avoiding antibiotics, apart from a 3 day course for a proven infection with a pathogen such as Escherichia coli. Then alkalinising the urine with citrate or bicarbonate preparations from a high street chemist may help with symptoms and prevent further invasion of the urinary tract, while the normal distribution and balance of the commensal flora is re-established. She commented that the earlier in the progression of the condition this is carried out, the greater the likelihood of success in gradually rendering the patient symptom-free.

D-mannose has been reported to help in this condition [6, 7]. It is thought to act by inhibiting bacterial adhesion to the urothelial cells [3, 4]. Use of non-steroid anti-inflammatory drugs, such as ibuprofen, may provide some help in addition to other therapies, by calming local nerve pathways. A consideration to keep in mind is that some vaginal preparations may occasionally irritate perineal areas. Cranberry juice is no longer thought to be useful and it may make symptoms worse. Like vitamin C, it acidifies the urine.

A short course of azithromycin may be useful in this condition, mainly for its anti-inflammatory effect and high tissue concentration (STDs having been ruled out). However, this needs further investigation.

1. Harding C, Mossop H, Homer T et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women BMJ 2022:376:e068229 doi: 10.1136/bmj-2021-0068229

2. Lo TS, Hammer KDP, Zegarra M, Cho WCS Methenamine: a forgotten drug for preventing recurrent urinary tract infection in a multidrug resistance era. Expert Review of Anti-infective Therapy 2014; 12 (5): 549-554 https://doi.org/10.1586/14787210.2014.904202

3. Hoffmann TC, Bakhit M, Del Mar C. Methenamine hippurate for recurrent urinary tract infections. Commentary. BMJ 2022; 376: o533 http://dx.doi.org/10.1136/bmj.o533

4. Methenamine hippurate / drug-BNF. https://bnf.nice.org.uk › drug › methenamine-hippurate

5. Maskell RM The natural history of urinary tract infection in women, Medical Hypothesis 2010;74:802-806 doi:10.1016/j.mehy.2009.12.011

6. Kranjčec B, Papeš D, Altarac S. D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol. 2014 Feb;32(1):79-84. doi: 10.1007/s00345-013-1091-6. Epub 2013 Apr 30.

7. Domenici L; Monti M; Bracchi C; Giorgini M; Colagiovanni V; Muzii L; Benedetti Panici P. D-mannose: a promising support for acute urinary tract infections in women. A pilot study. European Review for Medical & Pharmacological Sciences. 2016; 20(13):2920-5. PMID: 27424995.

Competing interests: No competing interests