A Clinical Trial of Extended (High) Treatment Dose Antibiotics in Combination With Methenamine Hippurate Compared to the Standard of Care (Either Prophylactic (Low) Dose Antibiotic Treatment or Methenamine Hippurate) in Females With Chronic Urinary Tract Infection

Chronic Urinary Tract Infection (UTI) is a type of UTI where symptoms are constant and occur every day, unlike recurrent UTIs, which come and go with symptom-free breaks in between. Current treatment for chronic UTI within the NHS is based on recommended guidelines for recurrent UTI. The standard approach typically includes one of the following treatments: * Long-term, prophylactic (low) dose daily antibiotic (where medication is used at low doses to try to prevent symptoms reoccurring). * Long-term use of a urinary antiseptic (which helps keep your urine bacteria free), called methenamine hippurate. These often do not work for people with chronic UTI, and symptoms can persist. Moreover, standard urine tests may fail to detect infections, making diagnosis and treatment more challenging. The EAT-UP trial will investigate whether longer courses of treatment (higher) dose antibiotics combined with methenamine hippurate (a urinary antiseptic) are a more effective treatment at reducing levels of infection and symptoms than standard of care treatments (as described above).

EAT-UP is a UK multi-centre, randomised, open label, parallel-group, superiority, interventional phase II trial, aiming to recruit 192 female participants. Participants will undergo screening to evaluate their eligibility to participate in the trial. If eligible, participants will be randomly assigned into one of two groups: Group 1 will receive a treatment dose antibiotic in combination with the urinary antiseptic, methenamine hippurate (1 g twice daily). The treating clinician will select one of the following antibiotics based on the individual needs of the participant, such as their medical history, concomitant medications and any known allergies: * Cefalexin (500mg four times daily), or * Nitrofurantoin (100mg twice daily), or * Trimethoprim (200mg twice daily) Group 2 will receive a low-dose prophylactic antibiotic or the urinary antiseptic, methenamine hippurate. The treating clinician will select one of the following treatments based on the individual needs of the participant, such as their medical history, concomitant medications and any known allergies: * Amoxicillin (250mg once daily), or * Cefalexin (125mg once daily), or * Nitrofurantoin (50mg once daily), or * Trimethoprim (100mg once daily), or * Methenamine Hippurate (1g twice daily) Participants will be taking trial medication for 12 weeks and will be required to attend clinic for assessments every 4 weeks. Participant will complete questionnaires and provide blood, urine, and perineal (the area between the vagina and anus) swabs samples.

Inclusion Criteria: 1. A diagnosis of chronic UTI, without structural or functional urinary tract abnormality\*, defined as daily persistent symptoms affecting storage (urinary frequency, urgency or urge incontinence) and urinary tract pain symptoms (including bladder pain, urethral pain, or dysuria), for at least 3 months prior to the screening visit, with previously associated transient symptomatic improvement to antibiotic treatment for UTI, which in the opinion of the delegated clinician is secondary to chronic urinary tract infection. 2. A fresh urine microscopy examination showing ≥20 white blood cells/µl of urine at the screening visit. 3. Female\*\* patients. 4. Aged ≥18 years. 5. Screening blood result of eGFR ≥45ml/min/1.73m2. 6. Able and willing to attend trial visits and comply with all study procedures for the duration of the trial. 7. Able and willing to provide informed consent prior to any study related assessments and/or procedures. * A structural or functional abnormality may include kidney reflux, current or long-term catheter use, renal transplant, diversion surgery, renal stones, grade 2 or above utero-vaginal prolapse or incomplete bladder emptying. * For the purposes of this trial, a female will be defined as an individual assigned female at birth who has a female urinary tract. Exclusion Criteria: 1. Inability to take at least one of the following antibiotics: Cefalexin, Nitrofurantoin, or Trimethoprim, at prophylactic and treatment dose according to NICE guidelines, and/or the Summary of Product Characteristics (such as hepatic or renal dysfunction), or any other medical contraindications. 2. Inability to take methenamine hippurate due to medical contraindications. 3. Current use of immune-modulating drugs for the treatment of chronic illnesses such as rheumatoid arthritis, chronic lung disease, any other autoimmune conditions or cancer. 4. Current use of Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors\*. 5. A current diagnosis of bladder cancer. 6. A diagnosis of an active sexually transmitted infection or a recent diagnosis of a sexually transmitted infection within the last 3 months of the screening visit. 7. Previous use of an antibiotic at treatment dose as per NICE guidelines for more than 14 consecutive days for treatment of UTI in the last 3 months prior to the screening visit. 8. Pregnancy (or planned pregnancy during trial participation) and/or breastfeeding. 9. Women of childbearing potential that are unable/unwilling to use an acceptable method of contraception (as described in section 3.4.1) to avoid pregnancy for the duration of the trial and for 1 week after the last dose of trial medication. 10. Current participation in another clinical trial of a device, interventional medicinal product, advanced therapy, or surgical procedure; or previous participation within 6 months of the screening visit. 11. Any medical condition or previous treatment which in the investigator's opinion compromises the potential participant's ability to participate. * Patient's must not have taken a Sodium-Glucose Transport Protein 2 (SGLT2) inhibitor within 24 hours before the screening visits to be eligible for the trial.