Lawrenz Matthew B, Biller Ashley E, Cramer Daniel E, Kraenzle Jennifer L, Sotsky Julie B, Vanover Carol D, Yoder-Himes Deborah R, Pollard Angela, Warawa Jonathan M
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.
Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Pathog Dis. 2015 Jul;73(5). doi: 10.1093/femspd/ftv025. Epub 2015 Apr 9.
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.
铜绿假单胞菌是一种机会性病原菌，能够引发多种疾病表现，包括严重的细菌性肺炎。最近，临床报告显示耐多药（MDR）菌种的医院感染有所增加，其中包括铜绿假单胞菌的MDR菌株。为了快速评估针对MDR感染的新疗法的疗效，需要开发高度可重复且经过验证的动物模型用于临床前测试。在此，我们描述了两种用于研究MDR铜绿假单胞菌呼吸道疾病的小鼠模型的特征。我们使用非侵入性气管内滴注方法对这些模型进行了评估和比较，并确定了每种模型的50%致死剂量、感染过程、疾病的生物统计学参数以及肺炎发展程度。此外，我们测试了美罗培南作为概念验证性疗法，并报告了疗效数据，表明白细胞减少模型可作为测试新型疗法的强大临床前模型。
