NHS Ayrshire & Arran example guideline 2: Guideline for the use of Uromune® uti vaccine for the management of resistant uti's in women or men aged ≥ 18 years (unlicensed product)

There is a cohort of patients who have repeated frequent urinary tract infections (UTIs) that cause systemic upset and require either oral, parenteral or intravesical antibiotics to achieve symptom relief. These patients have to repeatedly attend both primary and secondary care for treatment and their quality of life is poor, both because of the symptoms the infection has caused, and because of their repeated need to seek medical treatment. Some of these patients have their bladders intact, whilst others have had bladder augmentations with both groups needing to perform intermittent catheterisation. Some patients have had previous urinary diversions and there are a small number of men with chronic bacterial prostatitis.

The purpose of this guideline is to provide a framework to ensure that Uromune® is prescribed appropriately and used safely for specific patents.

Uromune® is a urinary tract infection immunostimulant. It is a colourless liquid contained in 2 x 9ml bottles with a spray nozzle which contains four deactivated bacteria (Klebsiella pneumoniae 25%, Escherichia coli 25%, Enterococcus faecalis 25% and Proteus vulgaris 25%).

Uromune® is an unlicensed product made available by Syner-Med Ltd. with the authorisation from MHRA for importation and supply based on individual basis via Name Patient Programme (NPP) on the request of qualified healthcare professionals. Prior to any Purchase Order, Syner-Med Ltd (MHRA requirement) request that a “named patient 3 month supply form” (see appendix (1)) supplied by them is completed and signed by the prescribing physician (this form only needs to be completed once by each prescribing physician).

Please refer to NHS A&A Code of Practice for more information on the ‘unlicensed’ use of medicines.

Within NHS Ayrshire & Arran, Uromune® will only be initiated by a Consultant Urologist, with a specialist interest in female urology.

The Urology Consultant initiating therapy will:

• consent the patient
• provide the patient with written and verbal information about the treatment
• ensure the patient has been adequately trained to administer the treatment
• prescribe Uromune® for so long as it is indicated (3 month supply followed by 9 months without – can be re-prescribed after 12 months)
• send a standard letter to patient’s GP on commencement of Uromune® including the rationale for treatment, treatment regimen, potential complications, and contact numbers (can be dictated by Continence Nurse Specialist).

Women or men who suffer recurrent urinary tract infections/chronic bacterial prostatitis i.e. >3 proven urinary tract infections in any 12 month period, >2 in 6 months OR at least 1 infection requiring hospital admission in any 12 month period with a background of recurrent urinary tract infections. In addition:

• They must have culture proven infections of E.coli, Klebsiella, Proteus or Enterococcus bacteria isolated.
• These patients may have failed on long term oral antibiotic prophylaxis or be intolerant to the oral non-antibiotic agents currently available for this indication.
• The guideline should only be used when all conventional measures to reduce the frequency of urinary tract infections have failed, including a trial of long term, low dose antibiotic prophylaxis; Cystistat® or iAluril® instillations, use of cranberry juice or capsules; use of D-mannose; use of topical oestrogens; high fluid intake and frequent voiding’ and a check of intermittent self catheterisation technique where applicable. An underlying treatable cause for infections will also have been ruled out with upper tract imaging and cystoscopy.
• Patients should have been considered for intravesical gentamicin and either:
  • failed to respond or developed resistance OR
  • were physically unable to perform intermittent catheterisation to allow self-administration of the gentamicin.
• The patient should be made aware by the clinicians responsible for ongoing care that the treatments is of limited benefit and has not been subjected to detailed research. They should then take part in a full discussion and decide for themselves whether they want to use this novel treatment. This discussion must be documented in the patient’s medical notes along with the patient’s consent if they decide to proceed.

Dosage: Uromune® sublingual spray; 2 puffs once daily for 3 months.

Duration: Therapy is prescribed for 3 months, with 9 months rest. Uromune® can be prescribed again after 12 months in the absence of complications or a change in circumstances.

Administration: Uromune® is a sublingual spray that is taken once a day as 2 puffs under the tongue. Patients should avoid eating or drinking for one hour before and after administration.

• Prescriptions will be written by the Urology Consultants only—either on a hospital out -patient script (see appendix (2)) or on a discharge letter. A 3 month only prescription will be supplied.
• A three month supply is made of 2 x 9ml bottles of Uromune® supplied from Syner-Med Ltd and dispensed from hospital pharmacy.
• The vaccine must be stored in a fridge.
• No other equipment is required to be supplied for use.

Patients will be reviewed by the Continence Specialist Nurses at day 7, 1 month, 3 months, 6 months, 9 months and 12 months. At 6 and 12 months there will also be a Consultant Urologist review. At 12 months a decision will be made on the benefit of a repeat prescription.

At each review, patients will be assessed for clinical benefits of treatment, reduction in hospital/ high level of care with sepsis admissions, adverse drug reactions and a decision made regarding continuation of treatment (relevant at day 7, 1 month and 12 month review).

If no clinical benefit was demonstrated at the 12 month review Uromune® should not be prescribed again.

If any significant adverse effects develop at any time during treatment, then Uromune® will be discontinued.

Uromune® may cause the following side effects:

• Heat sensation, swelling or itching in the mouth.
• Disturbances of gastro-intestinal tract, such as abdominal pain.
• Mucosal inflammatory reaction.
• Post nasal drip –might settle spontaneously after 1 month.
• If you have asthma, may experience worsening of symptoms.
• If you have recurrent urosepsis, might experience urosepsis again.
• Pruritus may be experienced.
• Fever.
• Allergic reaction, especially for patient with a history of allergy or predispose to allergic reactions
  • If patient develops an allergic reaction – advise to stop taking for 1 week and use antihistamines/topical steroids. Once settles, patient should restart at half normal dose i.e. 1 spray daily for 1 week then increase to 2 sprays daily. If symptoms return stop immediately and contact urology.

The Medicines and Healthcare products Regulatory Agency (MHRA) yellow card scheme should be used to report any adverse effects which are serious, medically significant or result in harm from Uromune. This will be done online at www.mhra.gov.uk/yellowcard , via Yellow Card mobile app or via paper Yellow Card form found in BNFs.

An audit of all patients commenced on Uromune® will be undertaken within the urology department. Data recorded will include; efficacy of treatment, number/ type of hospital admissions due to UTIs, number of episode of symptomatic UTIs and side effects.

1. Scottish Intercollegiate Guidelines Network. (2020) SIGN 160 Management of Suspected Bacterial Lower Urinary Tract Infection in Adult Women. Scottish Intercollegiate Guidelines Network. Available from https://www.sign.ac.uk/media/1766/sign-160-uti-0-1_web-version.pdf.
2. European Association of Urology (EAU) guideline on urological infections. Available from https://uroweb.org/guidelines/urological-infections.
3. Yang B, Foley S. First experience in the UK of treating women with recurrent urinary tract infections with the bacterial vaccine Uromune®. BJU Int. 2018 Feb;121(2):289-292. doi: 10.1111/bju.14067.
4. Yang B, Foley S and Charlesworth P. (May 26, 2018) The First Experience in the United Kingdom of using the Novel Treatment Uromune in Men with Recurrent Urinary Tract Infections. British Association of Urological Surgeons.