TY - JOUR
T1 - Proof-of-principle study in a murine lung infection model of antipseudomonal activity of phage PEV20 in a dry-powder formulation
AU - Chang, Rachel Yoon Kyung
AU - Chen, Ke
AU - Wang, Jiping
AU - Wallin, Martin
AU - Britton, Warwick
AU - Morales, Sandra
AU - Kutter, Elizabeth
AU - Li, Jian
AU - Chan, Hak Kim
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - bacteriophage therapy
KW - Pseudomonas aeruginosa
KW - pulmonary infections
KW - murine model
KW - powder aerosols
UR - http://www.scopus.com/inward/record.url?scp=85041067600&partnerID=8YFLogxK
U2 - 10.1128/AAC.01714-17
DO - 10.1128/AAC.01714-17
M3 - Article
AN - SCOPUS:85041067600
SN - 0066-4804
VL - 62
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 2
M1 - e01714-17
ER -