Combatting AMR in UTIs

Urinary tract infections (UTIs) are among the most common bacterial infections, affecting millions of people worldwide. The term ‘UTIs’ encompasses infections in any part of the urinary system (the kidneys, ureters, bladder and urethra).

Most UTIs are caused by bacteria, particularly E. coli, which enter through the urethra and colonize the bladder. Treatment typically involves empiric use of broad-spectrum antibiotics, prescribed before the exact causative bacteria are identified. While convenient, this approach can be less effective than targeted therapy and contributes significantly to the growing threat of antimicrobial resistance (AMR). Broad antibiotic use places selective pressure on bacteria, allowing resistant strains to survive and multiply while sensitive ones are eliminated.

AMR has made many infections harder to treat, often requiring longer treatment courses and increasing healthcare costs. Antibiotics once reliable for UTI treatment are now frequently ineffective; a 2019 study found that 92% of urine samples contained bacteria exhibiting drug resistance¹. The problem is compounded by the fact that prescribing an ineffective antibiotic can result in a chronic UTI or in some cases, sepsis.

Women are estimated to suffer from UTIs up to 30 times more often than men². This is especially the case for recurrent and antibiotic resistant UTIs. This may be because of differences in physiology; women have a shorter urethra so bacteria are more likely to reach the bladder or kidneys.

The risk of urinary tract infections (UTIs) can increase during pregnancy and after menopause. In pregnancy, both anatomical changes - such as mechanical obstruction that disrupts urine flow - and hormonal shifts, particularly elevated progesterone levels, contribute to a higher UTI risk. If left untreated, UTIs during pregnancy can lead to serious complications like kidney infections, preterm birth, or low birth weight.

After menopause, declining oestrogen levels can lead to recurrent UTIs. Oestrogen plays a vital role in keeping the tissues of the urethra and vagina elastic and moist, partly by supporting collagen production. It’s been estimated that collagen in the vulva can decrease by up to 30% within the first five years after menopause. As oestrogen declines, these tissues become thinner and drier, causing irritation and muscle weakening. These changes make it easier for bacteria to enter the urethra and travel up to the bladder, increasing the likelihood of infection. Additionally, a lack of oestrogen allows the protective lactobacilli and other beneficial bacteria in the vaginal microbiome to be replaced by harmful, pathogenic bacteria.

Recently, we have seen the development of vaginal oestrogen-based treatments, which can be particularly helpful for UTIs in post-menopausal women. These therapies are affordable, safe, and easy to use, available in several forms such as creams, tablets, or vaginal rings that gradually release oestrogen directly to surrounding tissues. For example, Estring is a ring that is placed in the upper vagina and only replaced every 3 months.

Vaginal oestrogen has been shown to promote a healthy vaginal microbiome (e.g. by promoting the growth of beneficial Lactobacillus)³ and to reduce the incidence of UTIs.

Recently, several other approaches have been taken to develop alternative treatments to UTIs which mitigate the risk of AMR. For example, Fimbrion are developing mannosides as narrow-spectrum antimicrobials. These mannose-containing small molecules target the bacterial adhesin FimH, thereby preventing bacteria from being able to stick to the walls of the bladder⁴.

Another option that may offer an alternative to antibiotics is vaccination. A mucosal vaccine (Uromune®, also known as MV140) is being developed for the treatment of recurrent UTIs. The vaccine contains heat-inactivated whole bacterial cells from four species (Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris and Enterococcus Faecalis) and is sprayed under the tongue (sub-lingually) once per day⁵. It is pineapple flavoured! The vaccine has been shown to be associated with a significant reduction in the frequency of recurrent UTIs and related hospitalizations⁶.

These approaches can also be used hand-in-hand with better diagnostic methods. For example, Astrego’s AST (Antibiotic Susceptibility Testing) system aims to provide personalised treatment recommendations for patients with UTI by assessing the susceptibility of bacteria in a urine sample to 5 antibiotics (amoxicillin/clavulanic acid, ciprofloxacin, fosfomycin, nitrofurantoin, trimethoprim).

We are excited to see the development of innovative UTI treatments which combat AMR and contribute to improving women’s health. 

1. Ahmed SS, Shariq A, Alsalloom AA, Babikir IH, Alhomoud BN. Uropathogens and their antimicrobial resistance patterns: Relationship with urinary tract infections. Int J Health Sci (Qassim). 2019 Mar-Apr;13(2):48-55. PMID: 30983946; PMCID: PMC6436442.
2. Foxman, B. (2002). Epidemiology of urinary tract infections: Incidence, morbidity, and economic costs. American Journal of Medicine; 113(Suppl. 1A): 5S-13S.
3. Moore KH, Ognenovska S, Chua XY, Chen Z, Hicks C, El-Assaad F, Te West N, El-Omar E. Change in microbiota profile after vaginal estriol cream in postmenopausal women with stress incontinence. Front Microbiol. 2024 Mar 5;15:1302819. doi: 10.3389/fmicb.2024.1302819. PMID: 38505551; PMCID: PMC10948564.
4. Spaulding CN, Klein RD, Schreiber HL 4th, Janetka JW, Hultgren SJ. Precision antimicrobial therapeutics: the path of least resistance? NPJ Biofilms Microbiomes. 2018 Feb 27;4:4. doi: 10.1038/s41522-018-0048-3. PMID: 29507749; PMCID: PMC5829159.
5. Nickel JC, Doiron RC. An Effective Sublingual Vaccine, MV140, Safely Reduces Risk of Recurrent Urinary Tract Infection in Women. Pathogens. 2023 Feb 21;12(3):359. doi: 10.3390/pathogens12030359. PMID: 36986281; PMCID: PMC10052183.
6. Iftimie S, Ladero-Palacio P, López-Azcona AF, Pujol-Galarza L, Pont-Salvadó A, Gabaldó-Barrios X, Joven J, Camps J, Castro A, Pascual-Queralt M. Evaluating the use of Uromune® autovaccine in recurrent urinary tract infections: a pilot unicenter retrospective study in Reus, Spain. BMC Infect Dis. 2025 Jan 24;25(1):117. doi: 10.1186/s12879-025-10524-2. PMID: 39856603; PMCID: PMC11762519.