Prophylactic Antibiotics for the Treatment of Recurrent Urinary Tract Infections: Time to Consider the Alternatives?

As part of a series of blog posts surrounding World Patient Safety Day 2022's theme of 'Medication Safety', Chair of the RSCEd Urology SSB and Consultant Urologist Neil Fenn looks at prophylactic antibiotics for the treatment of recurrent urinary tract infections.

Antimicrobial resistance (AMR) is a real world problem. The UK ‘tackling antimicrobial resistance strategy (TARS)’ suggests we are heading towards a world, in which antibiotics no longer work¹. Poorly targeting and antimicrobial overuse are two of the main drivers for multi-resistance. AMR infections are estimated to cause 700,000 deaths each year globally, with a prediction that this will rise to 10 million, with a cumulative cost of $100 trillion by 2050².

Embedded within the TARS document, is a UK action plan to tackle AMR both within and outside our borders. These include reducing the need for and unintentional exposure to antimicrobials, optimising the use of antimicrobials and investing in innovation, supply and access to antimicrobials. There are four measures of success suggested, one of which is to reduce UK antimicrobial use in humans by 15% by 2024¹.

Urinary tract infections UTIs) are a frequent and common problem, particularly in women. Studies suggest that more than one in two women will have at least one infection during their lifetime. Recurrent urinary tract infections are defined as repeated UTI’s with a frequency of at least two episodes in the preceding six months or three episodes over the past year. Sadly one in four women who have had one UTI episode is likely to go on to develop frequent recurrences³. National and international guidelines have tended to use preventative strategies which recommend the use of daily low dose antibiotics as a treatment for recurrent UTI’s³. This position is no longer sustainable in a progressive antibiotic stewardship program.

Our understanding of the mechanism involved with developing UTI’s is improving thus allowing for the development of non-antibiotic agents to use as prophylaxis^3,4. These include lifestyle changes and various natural occurring products including probiotics, cranberry extracts and D’mannose. Vaginal oestrogens are also recommended in postmenopausal women. Methenamine Hippurate is another promising agent however a Cochrane systematic review concluded it may be effective but suggested large randomised controlled trials be conducted to confirm its efficacy. This has now been undertaken, reported and published in March’s BMJ, with very positive results⁵.

The ALTAR study is a multicentre, open label, randomised, non-inferior trial to test the efficacy of Methenamine Hippurate for the prevention of recurrent urinary tract infections compared to the current standard of care, daily low dose antibiotics⁵. The trial, led by Chris Harding, Consultant Urologist from Newcastle, recruited from eight centres around the UK over a two-year period. Women were aged over 18, with recurrent urinary infections requiring prophylactic antibiotics. The trial demonstrated that Methenamine Hippurate (1g twice daily) was non inferior to standard daily low dose antibiotics. Although the Methenamine Hippurate group did have a higher rate of UTI episodes, the absolute difference of 0.49 UTI episodes per year was felt to be of limited clinical consequence. More importantly there seemed to be increased rates of antimicrobial resistance development associated with the antibiotic arm as shown in the primary uropathogen E-coli testing. The treatment was well tolerated with 90% adherence with the allocated treatment in both arms. This well designed and run trial, provides good quality data to support a realistic alternative to long term low dose prophylactic antibiotics in this large group of patients.

As responsible clinicians we need to ensure that the treatments we offer to our patients are not only effective but also safe. The ALTAR study provides quality data for a move away from prophylactic antibiotics to treat recurrent UTIs. I would direct urologists and primary care physicians to access the paper, which was published in the British Journal of Medicine in March of this year⁵.

References:

1. TUK Government. Tackling antimicrobial resistance 2019-2024: The UK’s five-year national action plan.  https://www.gov.uk/government/publications/uk-5-year-action-plan-for-antimicrobial-resistance-2019-to-2024
2. Review on Antimicrobial Resistance, chaired by Jim O’Neill. Final report and recommendations. May 2016 https://amr-review.org/
3. National Institute for Health and Care Excellence. Guideline NG112, Urinary tract infection (recurrent): antimicrobial prescribing 2018. https://www.nice.org.uk/guidance/ng112/resources/urinary-tract-infection-recurrent-antimicrobial-prescribing-pdf-66141595059397
4. Alternative Therapeutic Options to Antibiotics for Treatment of Urinary Tract Infections: Front microbiol. 2020;11:1509. Loubert P et al.  http://doi.org/10.3389/fmicb.2020.01509
5. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women – multi centred open label, randomised non-inferior trial. Harding C et al. BMJ 2022; 376 doi: https://doi.org/10.1136/bmj-2021-0068229