Phage therapy of Pseudomonas aeruginosa infection in a mouse burn wound model

Phage therapy of Pseudomonas aeruginosa infection in a mouse burn wound model
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DOI:
10.1128/aac.01028-06
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发表时间:
2007-06-01
影响因子:
4.9
通讯作者:
Fralick, Joe A.
Fralick, Joe A.
中科院分区:
医学2区
文献类型:
--
作者:
McVay, Catherine S.;Velasquez, Marisela;Fralick, Joe A.

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通过三种不同的途径:肌肉注射(i.m.)、皮下注射(s.c.)或腹腔注射(i.p.),给烧伤损伤的小鼠注射由三种不同的铜绿假单胞菌噬菌体组成的单剂量铜绿假单胞菌噬菌体鸡尾酒。这些研究结果表明,单剂量的P. aeruginosa噬菌体鸡尾酒可以显著降低感染P. aeruginosa的热损伤小鼠的死亡率(从未治疗的6%生存率降至治疗后的22%至87%生存率),并且给药途径对治疗效果尤为重要,其中P.途径提供最显著的保护(87%)。噬菌体向血液、脾脏和肝脏传递的药代动力学表明,通过i.p.途径给药的噬菌体比通过i.m.或s.c.途径给药的噬菌体递送剂量更高、递送时间更早、递送时间更持久,这可能解释了这三种不同给药途径的疗效差异。
Mice compromised by a burn wound injury and subjected to a fatal infection with Pseudomonas aeruginosa were administered a single dose of a Pseudomonas aeruginosa phage cocktail consisting of three different P. aeruginosa phages by three different routes: the intramuscular (i.m.), subcutaneous (s.c.), or intraperitoneal (i.p.) route. The results of these studies indicated that a single dose of the P. aeruginosa phage cocktail could significantly decrease the mortality of thermally injured, P. aeruginosa-infected mice (from 6% survival without treatment to 22 to 87% survival with treatment) and that the route of administration was particularly important to the efficacy of the treatment, with the i.p. route providing the most significant (87%) protection. The pharmacokinetics of phage delivery to the blood, spleen, and liver suggested that the phages administered by the i.p. route were delivered at a higher dose, were delivered earlier, and were delivered for a more sustained period of time than the phages administered by the i.m. or s.c. route, which may explain the differences in the efficacies of these three different routes of administration.