Anti-biofilm activity of aerosolized phage vs. ciprofloxacin using an in vitro lung deposition platform
Mathura Thirugnanasampanthar1,2, Mellissa Gomez1,2, Myrna Dolovich1,3,4 & Zeinab Hosseinidoust1,2,5,6,7
1McMaster University, Hamilton, ON, L8S 4L8, Canada
2Department of Chemical Engineering
3Faculty of Health Sciences, Department of Medicine
4St. Joseph’s Healthcare, Firestone Research Aerosol Laboratory, Hamilton, ON, L8N 4A6, Canada
5School of Biomedical Engineering
6Michael DeGroote Institute for Infectious Disease Research
7Farncombe Family Digestive Health Research Institute
Summary
Pseudomonas aeruginosa is a bacterial pathogen frequently implicated in recurring, antibiotic-resistant airway infections. Aerosolized treatments for lower respiratory tract infections should include fine droplets <5 µm in aerodynamic size that can effectively penetrate and deposit at distal sites within the lungs. An in vitro platform composed of a six-stage viable cascade impactor fitted with transwell inserts containing P. aeruginosa biofilms was used to model different sites of infection within the airways. Biofilms were subsequently exposed to size-fractioned droplets of nebulized bacteriophage (phage) or the fluroquinolone antibiotic ciprofloxacin. Exposure to phage, regardless of the dose delivered by size-fractioned droplets, resulted in significant reduction of free-floating and adherent bacteria as compared to negative control samples. Conversely, antibacterial efficacy of ciprofloxacin exhibited a strong dose dependence. Only biofilms that received the highest dose of ciprofloxacin of 2.5 µg, delivered by ≥7 μm sized droplets, exhibited significant reduction in viability as compared to negative control samples. The superior performance of phage may be attributed to its self-replicating nature, allowing for on-site amplification from repeated cycles of infection, propagation, host cell lysis, and progeny virion release. Lacking this characteristic, intervention with nebulized ciprofloxacin proved to be dose restrictive. This study demonstrates the promise of inhaled delivery of lytic phages for tackling persistent deep lung infections as compared to conventional antibiotics.