Aerosolized delivery of ESKAPE pathogens for murine pneumonia models

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Murine pneumonia models are crucial for evaluating new antibacterials and immune responses against ESKAPE pathogens.
• Current models primarily use intranasal or intratracheal instillation, which may limit homogeneous pathogen distribution.
• A refined delivery method is needed for more accurate pharmacokinetic/pharmacodynamic (PK/PD) studies.

Purpose of the Study:

• To introduce and validate aerosol delivery of pathogens as a superior method for murine pneumonia models.
• To compare aerosol delivery with traditional instillation methods for PK/PD assessments.
• To establish a more natural and efficient route for respiratory infection modeling.

Main Methods:

• Utilized a nebulizer for aerosolized delivery of five ESKAPE pathogens to mice.
• Employed neutropenic and immunocompetent mouse models to assess bacterial burden.
• Analyzed bacterial burden at 2 hours post-inhalation and over time.

Main Results:

• Aerosol delivery achieved sustained bacterial burden in neutropenic mice for all five pathogens tested.
• Similar sustained bacterial burden was observed in immunocompetent mice for three out of five pathogens.
• Significant bacterial burden in lungs was evident as early as 2 hours post-inhalation.

Conclusions:

• Aerosol delivery provides homogeneous lung distribution, ideal for PK/PD studies requiring multiple analyses from single samples.
• This method mimics natural respiratory infection routes, offering a more relevant model.
• Aerosol delivery is a viable and refined alternative to intranasal administration for murine pneumonia models, particularly for antibacterial PK/PD evaluations.