Proof-of-Principle Study in a Murine Lung Infection Model of Antipseudomonal Activity of Phage PEV20 in a Dry-Powder Formulation

Abstract

Bacteriophage therapy is a promising alternative treatment to antibiotics, as it has been documented to be efficacious against multidrug-resistant bacteria with minimal side effects. Several groups have demonstrated the efficacy of phage suspension <i>in vivo</i> 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 a liquid formulation, including easy storage, transport, and administration. The purpose of this study was to assess the bactericidal activities of phage dry-powder formulations against multidrug-resistant (MDR) strain <i>Pseudomonas aeruginosa</i> FADDI-PA001 in a mouse lung infection model. Phage PEV20 spray dried with lactose and leucine produced an inhalable powder at a concentration of 2 × 10⁷ PFU/mg. <i>P. aeruginosa</i> lung infection was established by intratracheal administration of the bacterial suspension to neutropenic mice. At 2 h after the bacterial challenge, the infected mice were treated with 2 mg of the phage powder using a dry-powder insufflator. At 24 h after the phage treatment, the bacterial load in the lungs was decreased by 5.3 log₁₀ (<i>P</i> < 0.0005) in the phage-treated group compared with that in the nontreated group. Additionally, the phage concentration in the lungs was increased by 1 log₁₀ at 24 h in the treated group. These results demonstrate the feasibility of a pulmonary delivery of phage PEV20 dry-powder formulation for the treatment of lung infection caused by antibiotic-resistant <i>P. aeruginosa</i>.