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Phage therapy of Pseudomonas aeruginosa infection in a mouse burn wound model
Catherine S McVay1, Marisela Velásquez, Joe A Fralick
1Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA.
Abstract:
Mice compromised by a burn wound injury and subjected to a fatal infection with Pseudomonas aeruginosa were administered a single dose of a Pseudomonas aeruginosa phage cocktail consisting of three different P. aeruginosa phages by three different routes: the intramuscular (i.m.), subcutaneous (s.c.), or intraperitoneal (i.p.) route. The results of these studies indicated that a single dose of the P. aeruginosa phage cocktail could significantly decrease the mortality of thermally injured, P. aeruginosa-infected mice (from 6% survival without treatment to 22 to 87% survival with treatment) and that the route of administration was particularly important to the efficacy of the treatment, with the i.p. route providing the most significant (87%) protection. The pharmacokinetics of phage delivery to the blood, spleen, and liver suggested that the phages administered by the i.p. route were delivered at a higher dose, were delivered earlier, and were delivered for a more sustained period of time than the phages administered by the i.m. or s.c. route, which may explain the differences in the efficacies of these three different routes of administration.
Insights
A Pseudomonas aeruginosa phage cocktail significantly reduced mortality in burned mice infected with P. aeruginosa. Intraperitoneal administration offered the highest survival rate, highlighting the importance of delivery route in phage therapy efficacy.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacteriophage Therapy
Background:
- Pseudomonas aeruginosa infections pose a significant threat, especially in immunocompromised individuals such as burn wound patients.
- Bacteriophage therapy offers a promising alternative or adjunct to conventional antibiotics for treating bacterial infections.
Purpose of the Study:
- To evaluate the efficacy of a Pseudomonas aeruginosa phage cocktail in a murine model of burn wound infection.
- To determine the impact of different administration routes (intramuscular, subcutaneous, intraperitoneal) on phage therapy outcomes.
Main Methods:
- Mice with burn wounds were infected with Pseudomonas aeruginosa and treated with a single dose of a three-phage cocktail.
- Phages were administered via intramuscular (i.m.), subcutaneous (s.c.), or intraperitoneal (i.p.) routes.
- Survival rates and phage pharmacokinetics in blood, spleen, and liver were analyzed.
Main Results:
- The phage cocktail significantly increased survival rates in infected mice, from 6% to 22-87%.
- Intraperitoneal administration yielded the highest survival rate (87%), demonstrating superior efficacy.
- Pharmacokinetic data indicated higher, earlier, and more sustained phage levels in systemic circulation following i.p. administration.
Conclusions:
- A single dose of the Pseudomonas aeruginosa phage cocktail is effective in reducing mortality in a murine model of burn wound infection.
- The route of administration critically influences phage therapy efficacy, with i.p. delivery being the most effective.
- Optimized phage delivery kinetics likely contribute to the enhanced therapeutic outcomes observed with the i.p. route.
