Development of Phage Cocktails to Treat E. coli Catheter-Associated Urinary Tract Infection and Associated Biofilms

Abstract

High rates of antimicrobial resistance and formation of biofilms makes treatment of Escherichia coli catheter-associated urinary tract infections (CAUTI) particularly challenging. CAUTI affect 1 million patients per year in the United States and are associated with morbidity and mortality, particularly as an etiology for sepsis. Phage have been proposed as a potential therapeutic option. Here, we report the development of phage cocktails that lyse contemporary E. coli strains isolated from the urine of patients with spinal cord injury (SCI) and display strong biofilm-forming properties. We characterized E. coli phage against biofilms in two in vitro CAUTI models. Biofilm viability was measured by an MTT assay that determines cell metabolic activity and by quantification of colony forming units. Nine phage decreased cell viability by >80% when added individually to biofilms of two E. coli strains in human urine. A phage cocktail comprising six phage lyses 82% of the strains in our E. coli library and is highly effective against young and old biofilms and against biofilms on silicon catheter materials. Using antibiotics together with our phage cocktail prevented or decreased emergence of E. coli resistant to phage in human urine. We created an anti-biofilm phage cocktail with broad host range against E. coli strains isolated from urine. These phage cocktails may have therapeutic potential against CAUTI.

Antibiotic Resistance of E. Coli in Clinical Practice

“…In addition to Ceftriaxone, a decrease in E.coli sensitivity to Cifloproxacin, Cefepime, and a non-significant decrease in sensitivity to Tetracycline and several other drugs were observed. However, a relatively high efficacy in 2020 was observed for Imipinem (+16%), and sensitivity to Amikacin increased [3].…”

“…Prevention is also very important. It includes the raising awareness of the problem among all segments of the population, doctors and other health personnel [2,3,4,5]. E.coli bacteria occupy a special place in this case.…”

Migration of surface-associated microbial communities in spaceflight habitats

“…The narrow-host range specificity of phages combined with the ability of bacteria to rapidly develop defense mechanisms to survive infection could be considered as a limitation of this approach. However, the use of phage cocktails with a broader spectrum of infection has already proved to be very efficient in complement to antibacterial treatments in combating pathogen biofilms within medical devices [244]. We can anticipate that similar strategies could be also used successfully in a spacecraft environment.…”

Preparing the Bowel (Microbiome) for Surgery: Surgical Bioresilience

“…52 Antibiofilm phage cocktails have also been developed with a broad host range against Escherichia coli strains isolated from urine. 53 Advances in CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technologies and messenger ribonucleic acid vaccine technologies are also heralding a new dawn in precision antiviral and antimicrobial vaccines, and they are being leveraged to create therapeutic vaccines for cancer. 54 It is now at last conceivable that emerging vaccination technologies being developed against common surgical pathogens responsible for SSI, such as Staphylococcus aureus , 55 will finally become a reality.…”