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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DOI：
10.1128/aac.01714-17
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发表时间：
2018-02-01
影响因子：
4.9
通讯作者：
Chan, Hak-Kim
中科院分区：
文献类型：
--
作者：
Chang, Rachel Yoon Kyung;Chen, Ke;Chan, Hak-Kim
噬菌体疗法是抗生素的一种有前途的替代疗法，因为它已被证明对多重耐药细菌有效，副作用最小。几个研究小组已经证明了使用鼻内递送体内噬菌体悬浮液治疗肺部感染的功效;然而，尚未探索将噬菌体干粉施用至肺部。粉末制剂提供优于液体制剂的潜在优点，包括易于储存、运输和施用。本研究的目的是在小鼠肺部感染模型中评估噬菌体干粉制剂对多药耐药（MDR）铜绿假单胞菌FADDI-PA 001菌株的杀菌活性。用乳糖和亮氨酸喷雾干燥的噬菌体PEV 20产生浓度为2 × 10（7）PFU/mg的可吸入粉末。铜绿假单胞菌肺部感染通过向贫血小鼠气管内施用细菌悬浮液来建立。在细菌攻击后2小时，使用干粉吹入器用2 mg噬菌体粉末处理感染的小鼠。在噬菌体处理后24 h，与未处理组相比，噬菌体处理组的肺中细菌负荷降低了5.3 log（10）（P < 0.0005）。此外，在处理组中，肺中的噬菌体浓度在24小时增加了1 log 10。这些结果证明了噬菌体PEV 20干粉制剂的肺部递送用于治疗由耐药性铜绿假单胞菌引起的肺部感染的可行性。
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 x 10(7) 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 log(10) (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.