Phage therapy of Pseudomonas aeruginosa infection in a mouse burn wound model

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.

FIG. 1.

Pharmacokinetics of the phages in noninfected mice. A cocktail containing ∼3 × 10⁸ phage was injected i.p., i.m., or s.c. into uninjured, uninfected mice. Groups of mice (n = 3) were killed at 0.5 h hpi, 12 hpi, 24 hpi, 36 hpi, or 48 hpi. Tissues were removed and the numbers of PFU were determined by serial dilution and plating on PAO1^Rif. (A) PFU/gram liver; (B) PFU/gram spleen; (C) PFU/ml blood. Values are means ± standard errors of the means.