Development and evaluation of murine lung-specific disease models for Pseudomonas aeruginosa applicable to therapeutic testing.

Abstract

Pseudomonas aeruginosa is an opportunistic bacterial pathogen capable of causing a wide range of disease manifestations, including severe bacterial pneumonia. Recently, clinics have reported a rise in nosocomial infections with multidrug resistant (MDR) species, including MDR strains of P. aeruginosa. In order to quickly evaluate the efficacy of new therapeutics for MDR infections, highly reproducible and validated animal models need to be developed for pre-clinical testing. Here, we describe the characterization of two murine models to study MDR P. aeruginosa respiratory disease. We evaluated and compared these models using a non-invasive intratracheal instillation method and established the 50% lethal dose, course of infection, biometric parameters of disease and degree of pneumonia development for each model. Further, we tested meropenem as a proof-of-concept therapeutic and report efficacy data that suggests that the leukopenic model could serve a robust pre-clinical model to test novel therapeutics.

• Authors: Matthew B Lawrenz, Ashley E Biller, Daniel E Cramer, Jennifer L Kraenzle, Julie B Sotsky, Carol D Vanover, Deborah R Yoder-Himes, Angela Pollard, Jonathan M Warawa
• Journal: Pathogens and disease (Pathog Dis) Vol. 73 Issue 5 (Jul 2015) ISSN: 2049-632X [Electronic] United States
• PMID: 25857733 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © FEMS 2015. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Anti-Bacterial Agents
• Thienamycins
• Meropenem

Topics

• Animals
• Anti-Bacterial Agents (therapeutic use)
• Biometry
• Disease Models, Animal
• Drug Evaluation, Preclinical (methods)
• Drug Resistance, Multiple, Bacterial
• Female
• Lethal Dose 50
• Meropenem
• Mice, Inbred BALB C
• Pneumonia, Bacterial (drug therapy, microbiology, pathology)
• Pseudomonas Infections (drug therapy, microbiology, pathology)
• Pseudomonas aeruginosa (drug effects, growth & development)
• Thienamycins (therapeutic use)
• Treatment Outcome