title: 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: Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, KY 40202, USA Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors: Matthew B
authors: MB
authors: Lawrenz
authors: Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors: Ashley E
authors: AE
authors: Biller
authors: Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors: Daniel E
authors: DE
authors: Cramer
authors: Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors: Jennifer L
authors: JL
authors: Kraenzle
authors: Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors: Julie B
authors: JB
authors: Sotsky
authors: Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors: Carol D
authors: CD
authors: Vanover
authors: Department of Biology, University of Louisville, Louisville, KY 40202, USA;
authors: Deborah R
authors: DR
authors: Yoder-Himes
authors: Agile Sciences, Inc., Raleigh, NC 27606, USA.
authors: Angela
authors: A
authors: Pollard
authors: Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, KY 40202, USA Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA jonathan.warawa@louisville.edu.
authors: Jonathan M
authors: JM
authors: Warawa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001699:Biometry; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D007928:Lethal Dose 50; D000077731:Meropenem; D008807:Mice, Inbred BALB C; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development*; D013845:Thienamycins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem
keywords: MDR Pseudomonas aeruginosa; biometric endpoint criteria; intubation-mediated intratracheal (IMIT) inoculation; murine respiratory disease; therapeutic model