Proof-of-principle study in a murine lung infection model of antipseudomonal activity of phage PEV20 in a dry-powder formulation

Rachel Yoon Kyung Chang, Ke Chen, Jiping Wang, Martin Wallin, Warwick Britton, Sandra Morales, Elizabeth Kutter, Jian Li, Hak Kim Chan

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18 Citations (Scopus)

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 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 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 Pseudomonas aeruginosa 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. P. aeruginosa 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 (P <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 P. aeruginosa.

Original languageEnglish
Article numbere01714-17
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number2
DOIs
Publication statusPublished - 1 Feb 2018

Keywords

  • bacteriophage therapy
  • Pseudomonas aeruginosa
  • pulmonary infections
  • murine model
  • powder aerosols

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