title: Efficacy of bacteriophage therapy in a model of Burkholderia cenocepacia pulmonary infection.
abstract: The therapeutic potential of bacteriophages (phages) in a mouse model of acute Burkholderia cenocepacia pulmonary infection was assessed. Phage treatment was administered by either intranasal inhalation or intraperitoneal injection. Bacterial density, macrophage inflammatory protein 2 (MIP-2), and tumor necrosis factor alpha (TNF-alpha) levels were significantly reduced in lungs of mice treated with intraperitoneal phages (P < .05). No significant differences in lung bacterial density or MIP-2 levels were found between untreated mice and mice treated with intranasal phages, intraperitoneal ultraviolet-inactivated phages, or intraperitoneal lambda phage control mice. Mock-infected mice treated with phage showed no significant increase in lung MIP-2 or TNF-alpha levels compared with mock-infected/mock-treated mice. We have demonstrated the efficacy of phage therapy in an acute B. cenocepacia lung infection model. Systemic phage administration was more effective than inhalational administration, suggesting that circulating phages have better access to bacteria in lungs than do topical phages.
authors.affiliation: Department of Pediatrics and Communicable Disease, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carmody
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Gill
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Summer
authors.forename: Uma S
authors.initials: US
authors.lastname: Sajjan
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Gonzalez
authors.forename: Ryland F
authors.initials: RF
authors.lastname: Young
authors.forename: John J
authors.initials: JJ
authors.lastname: LiPuma
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001435:Bacteriophages; D001691:Biological Therapy; D019121:Burkholderia Infections / Q000628:therapy*; D042602:Burkholderia cepacia complex / Q000821:virology*; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D051379:Mice; D012141:Respiratory Tract Infections / Q000382:microbiology / Q000628:therapy*