Bacteriophage therapy of Pseudomonas aeruginosa in Cystic Fibrosis

Pseudomonas aeruginosa Pseudomonas aeruginosa is the second most common pathogen responsible for hospital-acquired bacterial pneumonia as well as ventilator-associated pneumonia, and the first causative agent of morbidity and mortality in cystic fibrosis (CF) patients. Although antibiotics are still an effective means of treating bacterial lung infections, the alarming rise of multidrug-resistant bacteria in hospitals has highlighted the need for new therapies. Bacteriophages – viruses infecting bacteria – have been proposed to treat human bacterial infections since their discovery in the early 20th century. However, after a short period of development, the advent of antibiotics led to this therapeutic approach being abandoned, except in Eastern Europe where bacteriophages are still used today to treat patients. During the past 20 years, studies in animal models have demonstrated the potential of bacteriophages. Recently the first phase II clinical trial on bacteriophage treatments of chronic otitis was published, and demonstrated the interest of using bacteriophages on multidrug resistant infections.

The effects of bacteriophage therapy on lung infections has only very recently been addressed in animal models. On the one hand, a proof of concept with a bioluminescent strain of P. aeruginosa showed that bacteriophages administrated intranasally had a rapid efficacy with respect to preventing and curing deadly lung infections. On the other hand, a clinical strain of Burkholderia cenocepacia isolated from a CF patient was used to show that the intraperitoneal administration of bacteriophages was more effective than intranasal applications in a non-deadly infectious model. This paper reports an evaluation in an animal model of the efficacy of curative and preventive bacteriophage treatments of lung infections using a multidrug resistant mucoid P. aeruginosa strain isolated from a CF patient.

Pulmonary Bacteriophage Therapy on Pseudomonas aeruginosa Cystic Fibrosis Strains: First Steps Towards Treatment and Prevention. (2011) PLoS ONE 6(2): e16963. doi:10.1371/journal.pone.0016963
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.

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