Multidrug-resistant bacteria are the cause of an increasing number of deadly
pulmonary infections. Because there is currently a paucity of novel antibiotics,
phage therapy—the use of specific viruses that infect bacteria—is
now more frequently being considered as a potential treatment for bacterial
infections. Using a mouse lung-infection model caused by a multidrug resistant
Pseudomonas aeruginosa mucoid strain isolated from a cystic
fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were
isolated from environmental samples and characterized. Bacteria and
bacteriophages were applied intranasally to the immunocompetent mice. Survival
was monitored and bronchoalveolar fluids were analysed. Quantification of
bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as
histology and immunohistochemistry analyses were performed. A curative treatment
(one single dose) administrated 2 h after the onset of the infection allowed
over 95% survival. A four-day preventive treatment (one single dose)
resulted in a 100% survival. All of the parameters measured correlated
with the efficacy of both curative and preventive bacteriophage treatments. We
also showed that in vitro optimization of a bacteriophage
towards a clinical strain improved both its efficacy on in vivo
treatments and its host range on a panel of 20 P. aeruginosa
cystic fibrosis strains. This work provides an incentive to develop clinical
studies on pulmonary bacteriophage therapy to combat multidrug-resistant lung
infections