Development of a broad spectrum antimicrobial to combat chronic lung infection

项目摘要 在过去的十年里，美国和世界其他地区的细菌耐药性已经达到了令人震惊的水平。这个 抗菌素耐药(AMR)病原体的细菌感染增加导致医疗保健增加 成本和积极临床结果的下降。根据疾病控制中心的抗生素 美国2019年耐药性威胁报告(2019 AR Threats Report)，超过280万抗生素- 美国每年都会发生耐药感染，超过3.5万人因此死亡。治疗癌症的新疗法 迫切需要控制这些由AMR病原体引起的感染，因为：(A) 需要住院的感染者人数仍然很高；和(B)过度使用抗生素导致 继续出现更多的多药耐药(MDR)菌株。 迫切需要开发具有广泛抗菌活性的新型抗菌化合物。 AMR细菌既耐受性好，又不太倾向于选择耐药菌株。 我们的长期目标是开发一种有效、安全的疗法来治疗被确定为关键和 疾病预防控制中心和世界卫生组织(世卫组织)高度重视。 我们寻求开发我们的先导抗菌肽CM-YPD1，具有广谱的抗临床活性 ESKAPE病原体的分离用于治疗越来越多的MDR感染患者。这项建议 重点介绍了用于治疗囊性纤维化患者慢性肺部感染的CM-YPD1的开发。我们的 多学科团队将学术和商业专业知识的独特组合结合在一起，将 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 多药耐药细菌感染。

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.