Anti-Pseudomonal activity of phage PEV20 in a dry powder formulation -- A proof-of-principle study in a murine lung infection model [PublishAheadOfPrint]

Bacteriophage therapy is a promising alternative treatment to antibiotics as it has been documented to be efficacious against multi-drug resistant bacteria with minimal side effects. Several groups have demonstrated the efficacy of phage suspension in vivo to treat lung infections using intranasal delivery; however, phage dry powder administration to the lungs has not yet been explored. Powder formulations provide potential advantages over liquid formulation, including easy storage, transport and administration. The purpose of this study is to assess the bactericidal activities of phage dry powder formulations against MDR strain Pseudomonas aeruginosa FADDI-PA001 in a mouse lung infection model. Phage PEV20 spray dried with lactose and leucine produced inhalable powder at a concentration of 2 x 10⁷ PFU/mg. P. aeruginosa lung infection was established by intratracheal administration of bacterial suspension to neutropenic mice. At 2 h post-bacterial challenge, the infected mice were treated with 2 mg of the phage powder using a dry powder insufflator. At 24 h post-phage treatment, bacterial load in the lung was decreased by 5.3-log₁₀ (p < 0.0005) in the phage-treated group when compared with the non-treated group. Additionally, the phage concentration in the lung was increased by 1-log₁₀ at 24 h in the treated group. These results demonstrate the feasibility of pulmonary delivery of phage PEV20 dry powder formulation for the treatment of lung infection caused by antibiotic-resistant P. aeruginosa.

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