Chronic UTI can be treated by extended courses of oral antibiotics or the instillation of antibiotics directly into the bladder. A patient’s symptoms, urine analysis and circumstances guide how a physician approaches treatment.
Extended course oral antibiotics
In a recently published ten-year patient led UK clinical study at the Lower Urinary Tract Symptoms Clinic within the Whittington Hospital London, 624 women were recruited and treated with high-dose narrow spectrum, first generation antibiotics alongside the urinary antiseptic Methenamine Hipurate (Hiprex) following unique urine microscopy. This protocol led to a significant reduction of symptoms in 64% of participants with a further 20% feeling very much better. The study noted: “The median number of patient visits was five (mean = 6.6; SD = 5), with 40% of women discharged after four visits and 80% within ten. Mean treatment length was 383 days. Some patients required long-term therapy, as attempts to withdraw treatment were associated with relapse. Others were treated successfully but requested long-term monitoring due to anxieties about disease recurrence”.
This study goes on to say: “In the medium term, this approach seems to be effective, although we have yet to collect data on the long-term success of this strategy. Given these data, an RCT is the next logical step. We believe that the correct design should be a comparative trial of the management protocol evolved here against treatment stipulated by current guidelines. We hope that these data will help in the design of future studies”. Clinical led studies into long term high dose antibiotic therapies are much needed especially given the reliance of medical guidelines around randomised control trials for evidence to support decisions and at present, reliance on protocols that advocate the usage of short course, low dose antibiotics for the management of urinary tract infections.
Why extended courses of antibiotics rather than the use of prophylaxis?
Elsewhere on this site, we have discussed how a chronic infection develops and the issue of biofilm infections or embedded persister cells within the bladder wall. These types of infections mean that an extended approach to treatment is needed.
The thinking behind this extended regime is that bacteria which do emerge from a biofilm or from embedded bladder wall cells can be targeted and eradicated before they are able to reattach to the bladder wall forming new communities of infection. However, a biofilm in itself, presents a particular challenge because of its ability to evade penetrating antimicrobial therapies. No low dose, short course of antibiotics will successfully challenge a biofilm once established. The UK patient led study mentioned above, demonstrated that antibiotic treatment is needed for often over a year and some patients require medication for a much longer period. The clinicians took a long-term targeted approach to biofilms and the issue of persister cells deep in the bladder wall which can lie dormant for months or even years. If these persisters begin to multiply then they recognised that there is a need for ongoing antibiotic management at an appropriate dose.
This method of treatment is different to that offered of low dose prophylaxis or preventative antibiotics which can be prescribed for around 3-6 months. Low dose or preventative antibiotics are an approach to treat acute attacks or to prevent one occurring if there are known triggers rather than the management of ongoing symptoms that a chronic infection can cause. However many find that whilst the antibiotics provide relief of their symptoms, once the course is completed, the problem comes back and their clinician is often reluctant to prescribe further antibiotics because of antimicrobial resistance.
Prophylaxis or preventative antibiotic treatment can lead to eventual antimicrobial resistance (AMR) because of:
- The low-level antibiotic dose leading to the mutation of bacteria to that antibiotic
- The bacterial response to antibiotics. Bacteria can modify their cell surfaces.This makes it more difficult for antibiotics to penetrate bacterial cells.
- The antibiotic prescribed doesn’t affect the infection causing bacteria
- Bacteria can evade antibiotics when they are embedded intracellular or biofilm infections
Use of oral antibiotics – reactions and side effects
Antibiotic use is widespread. As we know, used properly, antibiotics manage life-threatening infections, but as with any chemical compound sides effects can occur.
NHS England explain the most common reactions to antibiotics.
Always tell your specialist of previous reactions or allergies to medications during your consultations. Explain any other health issues that may be impacted by the use of antibiotics and if you are already prescribed antibiotics or other medications for separate health conditions.
Your specialist should explain possible side effects of your prescription during your appointment and your pharmacist can provide further information. It’s always worth also reading the patient information leaflet provided with your medication.
Any medication has possible side effects. You should tell your specialist about any side effects and reactions immediately.
Clinicians recommend that if you are on a long term protocol, blood tests for liver function should take place every three to six months. You can usually arrange these through your GP or within clinic if this service is available. Your GP should notify you if there are result abnormalities and your specialist can advise on whether to decrease or stop antibiotics as a result.
One of the unwanted side effects of taking oral antibiotics is their disruption of friendly microbes in the gut. This can lead to the rise of fungal infections (Thrush or Candida). If you already have issues with systemic or vaginal candida, talk to your specialist before starting treatment.
Find out more about treating thrush.
We explain the importance of healthy gut bacteria.
Antibiotic bladder instillations
Antibiotic bladder instillations may be a treatment of last resort considered by clinicians for patients who either have major systemic side effects using oral antibiotics, poor outcome from their use or require a localised rather than oral route. They should not be confused with bladder GAG layer instillations where the aim is to repair the outer GAG layer of the bladder wall for those patients diagnosed with Interstitial Cystitis.
Patients undergoing renal transplants and those with spinal injuries and neuropathic/neurogenic bladders often have major issues with UTI. Neurogenic bladder is the name given to a number of urinary conditions in people who lack bladder control due to a brain, spinal cord or nerve problem. This nerve damage can be the result of diseases such as multiple sclerosis (MS), Parkinson’s disease or diabetes. Multi-resistance often occurs from the use of oral antibiotics and catheter related infections can include biofilm formation on the catheter. They can have much higher rates of UTI than the general population.
What issues are there with bladder instillations?
- There are no large randomised control studies to demonstrate long term efficacy for the management of chronic urinary tract infections using bladder instillations.
- Studies relating to patients without neurogenic bladder problems or those who have undergone renal surgery focus on the replenishment of the GAG layer in the bladder. The European Urological Association noted:“A recent review of 27 clinical studies concluded that large-scale trials are urgently needed to assess the benefit of this type of therapy. Therefore, no general recommendation is possible at this stage”. This Cochrane Review published in 2016 confirms these findings.
- There are no standardised treatment regimes – instillations in trials have been offered daily for a week, every third day or once a week
- Antibiotics used in instillations are often generic medications (rather than those that are exclusively patented) thus no pharmaceutical manufacturing company has carried out its own trials on generic antibiotics used in instillations. This means that clinicians often have to develop their own treatment regimes – you may come across the words “rescue instills” which can include not only an antibiotic but also a steroid and gag layer replenishment agent.
- It is invasive which makes it logistically awkward and adds to the treatment expense offered to patients by local clinical commissioning groups and hospitals
- The usage of catheters may introduce further bacteria into an infected bladder
Antibiotics and persister cells
One of the key issues in the treatment of a chronic UTI is the known problem of persister cells. These are infected bacterial cells which lie dormant deep within the bladder wall. Whilst the antibiotic options covered above will target those bacterial cells which are either actively dividing on the wall of the bladder, are newly introduced into the bladder via the urethra or have been shed into the urine by the immune system response, ongoing treatment options must take into account the problem of persister cells.
Flares often occur when dormant bacteria are stimulated, break out of their own cells and seek new cells to colonise. The immune system reacts accordingly causing an increase in symptoms. It is critical that ongoing antibiotic coverage is available during these periods. Discuss with your chronic UTI specialist the most appropriate management options to suit you.
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