Expanding clinical phage microbiology: simulating phage inhalation for respiratory tract infections

Area of Science:

• Microbiology
• Biotechnology
• Respiratory Medicine

Background:

• Antibiotic resistance in respiratory tract infections necessitates novel therapeutic strategies.
• Phage therapy presents a promising alternative, with inhalation as a potential delivery route.
• Efficient phage delivery via inhalation requires rigorous evaluation.

Purpose of the Study:

• To develop and validate an in vitro model for assessing phage delivery through inhalation.
• To quantify viable phage loads after nebulization and delivery in a realistic airway model.
• To identify factors influencing phage viability during inhalation therapy.

Main Methods:

• Eight bacteriophages targeting common cystic fibrosis pathogens were aerosolized using a jet nebulizer.
• A real-scale, CT-derived 3D human airways model coupled with a breathing simulator was used.
• Viable phage loads were quantified at the nebulizer output and tracheal level.

Main Results:

• Phage inhalation demonstrated a variable reduction in viable phage titres, mainly attributed to the nebulization process.
• No correlation was observed between phage delivery efficiency and phage physical or genomic characteristics.
• The model allowed for quantitative assessment of phage loss during simulated inhalation.

Conclusions:

• Nebulization is a critical step influencing phage viability for inhalation therapy.
• Phage delivery is not solely dependent on physical or genomic properties, necessitating optimized nebulization protocols.
• Tailored, patient-specific in vitro models are crucial for optimizing phage therapy success in respiratory infections.