title: Toward modern inhalational bacteriophage therapy: nebulization of bacteriophages of Burkholderia cepacia complex.
abstract: Antibiotic-resistant bacterial infections have renewed interest in finding substitute methods of treatment. The purpose of the present in vitro study was to investigate the possibility of respiratory delivery of a Burkholderia cepacia complex (BCC) bacteriophage by nebulized aerosol administration. Bacteriophages in isotonic saline were aerosolized with Pari LC star and eFlow nebulizers, at titers with mean value (standard deviation) of 2.15 x 10(8) (1.63 x 10(8)) plaque-forming unit (PFU)/mL in 2.5-mL nebulizer fills. The breathing pattern of an adult was simulated using a pulmonary waveform generator. During breath simulation, the size distributions of the nebulized aerosol were measured using phase doppler anemometry (PDA). Efficiency of nebulizer delivery was subsequently determined by collection of aerosol on low resistance filters and measurement of bacteriophage titers. These filter titers were used as input data to a mathematical lung deposition model to predict regional deposition of bacteriophages in the lung and initial bacteriophage titers in the liquid surface layer of each conducting airway generation. The results suggest that BCC bacteriophages can be nebulized successfully within a reasonable delivery time and predicted titers in the lung indicate that this method may hold potential for treatment of bacterial lung infections common among cystic fibrosis patients.
authors.affiliation: Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Laleh
authors.initials: L
authors.lastname: Golshahi
authors.forename: Kimberley D
authors.initials: KD
authors.lastname: Seed
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Dennis
authors.forename: Warren H
authors.initials: WH
authors.lastname: Finlay
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D001424:Bacterial Infections / Q000209:etiology / Q000628:therapy; D001435:Bacteriophages; D042602:Burkholderia cepacia complex / Q000821:virology*; D003550:Cystic Fibrosis / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D014018:Tissue Distribution
chemical_list: D000336:Aerosols