> Details

Guillon, Antoine; Pardessus, Jeoffrey; L'Hostis, Guillaume; Fevre, Cindy; Barc, Celine; Dalloneau, Emilie; Jouan, Youenn; Bodier‐Montagutelli, Elsa; Perez, Yonatan; Thorey, Camille; Mereghetti, Laurent; Cabrera, Maria; Riou, Mickaël; Vecellio, Laurent; Le Guellec, Sandrine; Heuzé‐Vourc'h, Nathalie

Inhaled bacteriophage therapy in a porcine model of pneumonia caused by Pseudomonas aeruginosa during mechanical ventilation

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: Inhaled bacteriophage therapy in a porcine model of pneumonia caused by Pseudomonas aeruginosa during mechanical ventilation
  • Contributor: Guillon, Antoine; Pardessus, Jeoffrey; L'Hostis, Guillaume; Fevre, Cindy; Barc, Celine; Dalloneau, Emilie; Jouan, Youenn; Bodier‐Montagutelli, Elsa; Perez, Yonatan; Thorey, Camille; Mereghetti, Laurent; Cabrera, Maria; Riou, Mickaël; Vecellio, Laurent; Le Guellec, Sandrine; Heuzé‐Vourc'h, Nathalie
  • Published: Wiley, 2021
  • Published in: British Journal of Pharmacology, 178 (2021) 18, Seite 3829-3842
  • Language: English
  • DOI: 10.1111/bph.15526
  • ISSN: 0007-1188; 1476-5381
  • Origination:
  • Footnote:
  • Description: Background and Purpose 255Pseudomonas aeruginosa is a main cause of ventilator‐associated pneumonia (VAP) with drug‐resistant bacteria. Bacteriophage therapy has experienced resurgence to compensate for the limited development of novel antibiotics. However, phage therapy is limited to a compassionate use so far, resulting from lack of adequate studies in relevant pharmacological models. We used a pig model of pneumonia caused by P. aeruginosa that recapitulates essential features of human disease to study the antimicrobial efficacy of nebulized‐phage therapy.Experimental Approach(i) Lysis kinetic assays were performed to evaluate in vitro phage antibacterial efficacy against P. aeruginosa and select relevant combinations of lytic phages. (ii) The efficacy of the phage combinations was investigated in vivo (murine model of P. aeruginosa lung infection). (iii) We determined the optimal conditions to ensure efficient phage delivery by aerosol during mechanical ventilation. (iv) Lung antimicrobial efficacy of inhaled‐phage therapy was evaluated in pigs, which were anaesthetized, mechanically ventilated and infected with P. aeruginosa.Key ResultsBy selecting an active phage cocktail and optimizing aerosol delivery conditions, we were able to deliver high phage concentrations in the lungs, which resulted in a rapid and marked reduction in P. aeruginosa density (1.5‐log reduction, p < .001). No infective phage was detected in the sera and urines throughout the experiment.Conclusion and ImplicationsOur findings demonstrated (i) the feasibility of delivering large amounts of active phages by nebulization during mechanical ventilation and (ii) rapid control of in situ infection by inhaled bacteriophage in an experimental model of P. aeruginosa pneumonia with high translational value.
  • Access State: Open Access