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    The International Society for Aerosols in Medicine

    Nathalie Heuzé-Vourc’h

    Nathalie Heuzé-Vourc’h

    Dr. Nathalie Heuzé-Vourc’h

    Inserm U1100  
    Research Center for Respiratory Diseases, Tours
    France

    Nathalie is a senior research scientist at Inserm in Tours, France and is leading a multidisciplinary team in the dedicated to ‘Aerosoltherapy and Biotherapeutics for Respiratory Diseases’. After graduating her Ph.D. in oncology in 2001, she trained in the division of pulmonary and critical care medicine at UCLA, California. She gained interest in biotherapeutics working in a start-up (Agensys Inc., California) developing anticancer antibodies. She was recruited at Inserm in 2005 and started working on the delivery of biotherapeutics by aerosol after joining Pr P. Diot’s team.

    Inhaled bacteriophages against respiratory infection

    Abstract

    Lung infections, in particular those due to Pseudomonas aeruginosa (Pa), are increasingly difficult to treat due to evolving antibiotic resistance. Bacteriophages are part of the foreseen complementary/ alternative therapies to antibiotics. In this study, a public-private consortium developed a phage cocktail for airway delivery, and assessed its preclinical efficacy and resistance to aerosolization.
    The cocktail was developed against a 43-strain Pa reference panel; it displayed 95% efficacy in vitro. In a murine model of acute Pa lung infection, local delivery, two hours post-infection allowed 85% survival of animals at 48h and a drop in bacterial lung count. To assess the impact of nebulization, the phage suspension was aerosolized with 4 different nebulizers. Mesh nebulization was the less deleterious to phages, resulting in 33.4% phage viability. Finally, the best drug & device was tested in a porcine model to mimic ventilator-associated pneumonia (VAP) and aerosol delivery. In larger animals, two aerosols allowed a high dose of phages to be delivered in the lungs and phage treatment led to a reduced bacterial load in both the tissue and broncho-alveolar lavage.

    Overall, the phage cocktail was efficient against Pa, both in vitro and in vivo. Nebulization was associated with 1/3 phage viability, which was sufficient to contain infection but not to resolve it in the VAP model. Further studies are required to evaluate phage in combination to antibiotics in VAP.