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

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

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: Antimicrobial Agents and Chemotherapy
Volume: 62
Number: 2
Date: 2017
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.1128/AAC.01714-17
ISSN: 0066-4804
Date Deposited: 03 Jan 2021 22:29

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.

Keywords: Pseudomonas aeruginosa; bacteriophage therapy; murine model; powder aerosols; pulmonary infections.

Copyright © 2018 American Society for Microbiology.

Chang, Rachel Yoon Kyung
Chen, Ke
Wang, Jiping
Wallin, Martin
Britton, Warwick
Morales, Sandra
Kutter, Elizabeth
Li, Jian
Chan, Hak-Kim
Last Modified: 03 Jan 2021 22:29

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