Phage-Based Elimination of CAUTI Biofilms
Research type
Research Study
Full title
Bacteriophage-Based Elimination of Biofilms in Catheters of Medical Patients with Urinary Tract Infections
IRAS ID
302607
Contact name
Martha Clokie
Contact email
Sponsor organisation
University of Leicester
Duration of Study in the UK
3 years, 4 months, 1 days
Research summary
Research Summary
Antibiotic resistance is a growing problem all over the word - it is estimated that by 2050, 10 million people will die every year from antibiotic-resistant infections alone, more than heart disease and cancer. Since no new antibiotics have been developed since the 1990s, researchers have been looking into alternative treatments, one of which are bacteriophages (aka phages), viruses that infect bacteria.
Phages are present everywhere in nature as part of the environment. They are very specific in their target, and only will attack only one species of bacteria. This means that phages do not attack our good bacteria (our microbiome), which conventional antibiotics do. Furthermore, they replicate inside the bacteria they kill, thus creating a self-dosing cycle which then disappears when the bacterial hosts have been wiped out.
My project involves two main species of bacteria, Escherichia coli and Klebsiella pneumoniae, which are both often associated with both serious illness and antibiotic resistance. My target is urinary tract infections (UTIs), which are a common occurrence in the public sector, and specifically catheter-associated UTIs (CAUTIs). These are almost guaranteed for patients with long-term urinary catheters, and have a 15% chance to spread to the bloodstream, and thus are a significant cause of both morbidity and mortality in older and more vulnerable patients.
The goal of this project is to develop, test, and optimise a bacteriophage and antibiotic cocktail, finding the best combination thereof, so as to treat CAUTIs. While testing a combined therapy cocktail using standard microbiology methods is possible, we want to test them in an environment as close to the human body as possible, and therefore the project would highly benefit from testing the treatment on patient catheters in the lab before moving on to animal models and then a clinical trial involving humans.
Summary of Results
4 out of the 15 patients recruited had catheters which had a detectable Escherichia coli infection, but none of the patients had catheters with detectable infections from any species of Klebsiella. All of the patients had multiple pathogenic organisms causing their infections, and also urinary sediment was present.
The 4 catheters with E. coli collected had the ends removed, and were cut down to 2x12 cm lengths, one of which was kept in the fridge and the other of which was connected to an Artificial Urinary Tract. Artificial Urine, which was made in the lab from a recipe published in 1995, was pre-mixed with bacteriophages, the good viruses, at a concentration that would more or less result in urine if the phages were given to the patient through their vein in an IV. It is important to note that the phages were targeting only the E. coli, despite the presence of the other infections alongside it.
The Artificial Urine-phage mixture was passed through the catheter slowly at about 1 ml every minute, or the rate of production of urine in healthy kidneys, for 5 days, to simulate a 5-day-long course of phage therapy.
After the 5 days were up, the catheter segments were removed from the Artificial Urinary Tract, air-dried, and then transported to a CT scanning facility at the University of Warwick, where they were imaged using a high-resolution micro-CT scanner. We decided to use the micro-CT scanner because it will not only give us images of the bacterial growth inside the catheters, but it can also measure its volume and thickness.
In all 4 catheters, the volume was reduced significantly for the phage-treated catheter segments:
• Patient 02:
o Biofilm volume decreased by 97%.
o Average biofilm thickness decreased by 60%.
o Maximum biofilm thickness decreased by 69%.
• Patient 03:
o Biofilm volume decreased by 54% (over half).
o Average biofilm thickness decreased by 42%.
o Maximum biofilm thickness decreased by 44%.
• Patient 09:
o Biofilm volume decreased by 99.96%.
o Average biofilm thickness decreased by 99%.
o Maximum biofilm thickness decreased by 98%.
• Patient 10:
o Biofilm volume decreased by 99.99%
o Average biofilm thickness decreased by 93%.
o Maximum biofilm thickness decreased by 93%.
These results show that phage therapy has great potential as a way to treat urinary tract infections, including those associated with catheters. In the case of the model used here, phages were very successful in clearing the biofilm caused by the E. coli infection, even in the presence of urinary sediment or several other co-occurring infections.REC name
London - Harrow Research Ethics Committee
REC reference
21/PR/1035
Date of REC Opinion
2 Sep 2021
REC opinion
Further Information Favourable Opinion