Development of a broad spectrum antimicrobial to combat chronic lung infection

项目摘要 在过去的十年里，细菌耐药性在美国和世界其他地区已经达到了令人震惊的水平。的 抗微生物剂抗性（AMR）病原体细菌感染的增加导致医疗保健的增加 成本和积极的临床结果下降。根据疾病控制中心的抗生素 美国2019年耐药威胁报告（2019 AR Threats Report）显示，超过280万种抗生素- 耐药感染每年在美国发生，超过35，000人因此死亡。的新疗法 迫切需要控制这些AMR病原体引起的感染，因为： 需要住院治疗的受感染个体仍然非常高;以及（B）过度使用抗生素导致 其他多药耐药（MDR）菌株的持续出现。 迫切需要开发具有广谱抗微生物活性的新型抗微生物化合物， AMR细菌耐受性良好，选择耐药菌株的倾向性低。 我们的长期目标是开发一种有效、安全的治疗MDR病原体的方法， CDC和世界卫生组织（WHO）的高度优先事项。 我们寻求开发我们的先导抗菌肽CM-YPD 1，其具有广谱抗临床 ESKAPE病原体的分离株来治疗越来越多的MDR感染患者。这项建议 专注于开发CM-YPD 1用于治疗囊性纤维化患者的慢性肺部感染。我们 多学科团队汇集了学术和商业专业知识的独特组合， 允许开发一种药物，可用于治疗越来越多的危及生命的患者， MDR细菌感染。

Project Summary Bacterial resistance has reached alarming levels in the US and other parts of the world in the past decade. The increase in bacterial infection with antimicrobial resistant (AMR) pathogens are resulting in increasing healthcare costs and a decline in positive clinical outcomes. According to the Center for Disease Control’s Antibiotic Resistance Threats in the United States 2019 report (2019 AR Threats Report), more than 2.8 million antibiotic- resistant infections occur in the U.S. each year, and more than 35,000 people die as a result. New therapies for controlling these AMR pathogen-induced infections are urgently needed because: (a) the mortality rate among infected individuals requiring hospitalization remains very high; and (b) overuse of antibiotics has resulted in continuing emergence of additional multi-drug resistant (MDR) strains. There is a dire need to develop novel antimicrobial compounds that have a broad spectrum of activity against AMR bacteria that are both well tolerated and have a low propensity to select for resistant strains of bacteria. Our long-term goal is to develop an effective, safe therapeutic to MDR pathogens determined to be critical and high priority by the CDC and the World Health Organization (WHO). We seek to develop our lead antimicrobial peptide, CM-YPD1, with broad-spectrum activity against clinical isolates of ESKAPE pathogens to treat the growing number of patients with MDR infections. This proposal focuses on development of CM-YPD1 for treatment of chronic lung infection in cystic fibrosis patients. Our multidisciplinary team brings together a unique combination of academic and commercial expertise that will permit the development of a drug that can be used to treat the growing number of patients with life-threatening MDR bacterial infections.