The following clinics based in Eastern Europe offer phage therapies.

• Eliava Institute, Tiblisi, Georgia
• Phage Therapy Centre Tiblisi, Georgia
• Phage Therapy Unit Polish Academy of Sciences

Controlled trials and studies are often limited in complementary and alternative medicine and involve small numbers of participants. They are often conducted under less rigorous controls, guidelines and environments than those undertaken for the development of new pharmaceutical medications such as antibiotics. Do your research, there should be clear, peer reviewed, empiric evidence as to the efficacy of complementary, unlicensed therapies such as phages rather than theorisation about how they may be beneficial in the treatment of acute, recurrent or persistent UTI. Phage therapy is as yet, an expensive unproven therapeutic option.

• Controlled trials and studies are often limited in complementary and alternative medicine and involve small numbers of participants. They are often conducted under less rigorous controls, guidelines and environments than those undertaken for the development of new pharmaceutical medications such as antibiotics. Do your research, there should be clear, peer reviewed, empiric evidence as to the efficacy of complementary, unlicensed therapies such as phages rather than theorisation about how they may be beneficial in the treatment of a chronic UTI.
• The cost of current treatment for patients not based in Eastern Europe. Clinics will offer inclusive packages for patient treatment including travel, accommodation and clinical care but at present phage therapy offered is for single, identified bacterial organisms rather than complicated multi-bacterial infections. It may be necessary for clinics to make different cocktails for treatment of the same infection, this increases the cost to the patient and may mean multiple visits to treat each individual bacterium identified.
• Bacterial specification – treatment is reliant on the identification of each bacterium via current standard laboratory testing protocols. This makes an assumption that these bacteria are responsible for a chronic UTI infection.
• Bacteria can evolve different receptors either before or during treatment; this can prevent phages from completely eradicating bacteria for as the bacteria evolve, bacteriophages must evolve as well to keep up with the ever changing bacteria. In the case all bacteria are eliminated, the specific phage might evolve and attack good bacteria in the specific area of administration.
• The need for banks of phages makes regulatory testing for safety harder and more expensive under current rules in most countries. Such a process would make difficult the large-scale use of phage therapy.
• Phage therapy is usually most effective with a cocktail injection, which is generally rejected by western health regulators. For phage therapy to be considered as treatment these authorities must change their regulatory stance on combination drug cocktails.
• Administration of phage therapy may mean the treatment is absorbed through the stomach wall into the bloodstream. For immuno-compromised patients, this could hypothetically worsen a patient’s condition. There are also similar concerns for patients with conditions such as Crohn’s disease, inflammatory bowel disease, and type 1 diabetes and at present these safety concerns still need to be addressed.
• The immune system response to phages also differs between individuals and is dependent on the specific phage strains used. To determine the safety of phage treatments for human health, future research will need to focus on human clinical trials as much of the current research on the immunological response to phages is limited to animal models
• Public awareness and education about phage therapy are generally limited to scientific or independent research rather than mainstream media. Much of this is down to reliance for many years on antibiotic therapies and at present there are insufficient randomised control trials showing success in the usage of phage therapy for countries to consider licensing the treatment in hospital and clinic settings.

There is a lack of peer-reviewed controlled clinical trials making it difficult to properly evaluate the effectiveness of such therapeutics by western standards; more observational studies of phage therapy in patient treatment are needed for it to be considered safe and effective for usage in the treatment of urinary tract infections. Currently, their use is limited and they are an unlicensed treatment.

Recent research published in 2018 has shown that bacteriophages are more abundant than bacteria themselves in the human bladder.

Loyola University, Chicago, and Loyola University Medical Center analysed the sequencing data from bacteria collected from the bladders of 181 female patients with and without urinary problems. The researchers identified more than 450 possible phage sequences within the majority of the nearly 200 bacterial genomes that they examined. More than half of these viral sequences were not found in any databases, suggesting that they could be phages unique to the urinary tract.

The authors found sequence similarities in phages from different women, which points to the possibility of a shared set of bladder phages. They also saw some variations in phage populations between the samples from women with and without urinary issues, including overactive bladder, incontinence, bladder pain, and urinary tract infection.

To determine whether the phage sequences they detected were intact and able to infect bacteria, the team isolated a new phage from an E. coli strain in the bladder. They captured electron micrographs of the purified phage and tested whether it could lyse bacteria in culture. Although the virus was originally integrated into the host’s genome, it was able to kill other bacteria, suggesting that it is indeed a functional bacteriophage.

They concluded “Our survey of lysogenic phages provides the first step in the process of unraveling the complex dynamics of phage-bacterium interactions within the urinary microbiota. Additional sequencing of the bacterial population within the bladder, coupled with further metagenomic sequencing of the urinary virome, is needed to both determine if a core “bladder phageome” exists and whether phages play a role in urinary health and disease.

Before antibiotics were discovered, there was research into bacteriophages as a treatment for human bacterial diseases. Bacteriophages attack only their host bacteria, not human cells, so they are potentially good candidates to treat bacterial diseases in humans.

After antibiotics were discovered, the phage approach was largely abandoned in many parts of the world. However, phages continued to be used for medical purposes in a number of countries, including Russia, Georgia, and Poland, where they remain in use today.

There is interest in bringing back the ‘phage approach’ elsewhere, as antibiotic-resistant bacteria become more and more of a problem. Much research is still needed to see how safe and effective phages are and whether phage treatment will benefit those with recurrent and chronic UTI.

Biotechnological advances have further expanded the potential of phage therapeutics. Current research on the use of phages specifically against multidrug-resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Universities in the US, Eastern and Western Europe, the UK, Asia and the Far East now have research centres dedicated to phage development for human clinical use and commercial agricultural use.

Antibacterial therapies, whether phage or antibiotic-based, each have relative advantages and disadvantages; accordingly, many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infections.

The bacterial range of phage therapy is generally narrower than that found in antibiotics. Most phages are specific for one species of bacteria and many are only able to lyse specific strains within a species. This limited host range can be advantageous, in principle, as phage therapy may result in less disruption to the normal body flora than commonly used antibiotics, which often disrupt gut flora and may result in opportunistic secondary infections by organisms such as Clostridium difficile, cause allergic reactions or tolerance issues. However this targeted approach may be considered to be a disadvantage of phages because the disease-causing bacterium must be identified before phage therapy can be successfully initiated. With multi bacterial infections such as recurrent or persistent cystitis, are the bacteria identified on urine testing the actual causative agents of the infection.