title: Bacteriophage Delivery by Nebulization and Efficacy Against Phenotypically Diverse Pseudomonas aeruginosa from Cystic Fibrosis Patients.
abstract: BACKGROUND
  The rise in antibiotic-resistant Pseudomonas aeruginosa and the considerable difficulty in eradicating it from patients has re-motivated the study of bacteriophages as a therapeutic option. For this to be effective, host range and viability following nebulization need to be assessed. Host-range has not previously been assessed for the Liverpool Epidemic Strain (LES) isolates that are the most common cystic fibrosis-related clone of P. aeruginosa in the UK. Nebulization studies have not previously been linked to clinically relevant phages.
  
  
  METHODS
  84 phenotypically variable isolates of the LES were tested for susceptibility to seven bacteriophages known to have activity against P. aeruginosa. Five of the phages were from the Eliava Institute (IBMV) and 2 were isolated in this study. The viability of the two bacteriophages with the largest host ranges was characterized further to determine their ability to be nebulized and delivered to the lower airways. Phages were nebulized into a cascade impactor and the phage concentration was measured.
  
  
  RESULTS
  The bacteriophages tested killed between 66%-98% of the 84 Liverpool Epidemic Strain isolates. Two isolates were multi phage resistant, but were sensitive to most first line anti-Pseudomonal antibiotics. The amount of viable bacteriophages contained in particles that are likely to reach the lower airways (<4.7 μm) was 1% for the Omron and 12% AeroEclipse nebulizer.
  
  
  CONCLUSIONS
  Individual P. aeruginosa bacteriophages can lyse up to 98% of 84 phenotypically diverse LES strains. High titers of phages can be effectively nebulized.
authors.affiliation: 1 Department of Infection, Immunity and Inflammation, University of Leicester , Leicester, United Kingdom .
authors.forename: Jaspreet Singh
authors.initials: JS
authors.lastname: Sahota
authors.affiliation: 1 Department of Infection, Immunity and Inflammation, University of Leicester , Leicester, United Kingdom .|2 Respiratory, Critical Care, and Anaesthesia, University College London , Institute of Child Health, London, Great Ormond Street Hospital, London, United Kingdom .
authors.forename: Claire Mary
authors.initials: CM
authors.lastname: Smith
authors.affiliation: 2 Respiratory, Critical Care, and Anaesthesia, University College London , Institute of Child Health, London, Great Ormond Street Hospital, London, United Kingdom .
authors.forename: Priya
authors.initials: P
authors.lastname: Radhakrishnan
authors.affiliation: 3 Department of Clinical Infection Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool , Liverpool, United Kingdom .
authors.forename: Craig
authors.initials: C
authors.lastname: Winstanley
authors.affiliation: 4 Eliava Institute of Bacteriophages , Microbiology, and Virology, Tbilisi, Georgia .
authors.forename: Marina
authors.initials: M
authors.lastname: Goderdzishvili
authors.affiliation: 4 Eliava Institute of Bacteriophages , Microbiology, and Virology, Tbilisi, Georgia .
authors.forename: Nina
authors.initials: N
authors.lastname: Chanishvili
authors.affiliation: 3 Department of Clinical Infection Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool , Liverpool, United Kingdom .
authors.forename: Aras
authors.initials: A
authors.lastname: Kadioglu
authors.affiliation: 1 Department of Infection, Immunity and Inflammation, University of Leicester , Leicester, United Kingdom .|2 Respiratory, Critical Care, and Anaesthesia, University College London , Institute of Child Health, London, Great Ormond Street Hospital, London, United Kingdom .
authors.forename: Chris
authors.initials: C
authors.lastname: O'Callaghan
authors.affiliation: 1 Department of Infection, Immunity and Inflammation, University of Leicester , Leicester, United Kingdom .
authors.forename: Martha Rebecca Jane
authors.initials: MR
authors.lastname: Clokie
mesh_terms: D001691:Biological Therapy / Q000379:methods*; D003550:Cystic Fibrosis / Q000382:microbiology*; D006801:Humans; D009330:Nebulizers and Vaporizers; D010641:Phenotype; D011552:Pseudomonas Infections / Q000628:therapy*; D017105:Pseudomonas Phages; D011550:Pseudomonas aeruginosa / Q000821:virology*
keywords: P. aeruginosa; bacteriophages; cystic fibrosis; nebulization