Development of a broad spectrum antimicrobial to combat chronic lung infection

开发广谱抗菌药物来对抗慢性肺部感染

基本信息

批准号：
10480299
负责人：
Colleen Doyle Cooper
金额：
$ 30.06万
依托单位：
CELDARA MEDICAL, LLC
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-10 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10480299
关键词：
Acinetobacter baumannii Acute Advanced Development Anti-Bacterial Agents Anti-Infective Agents Antibiotic Resistance Antibiotics Antimicrobial Resistance Bacteria Bacterial Infections Biological Assay Bronchiectasis COVID-19 COVID-19 pandemic Cause of Death Centers for Disease Control and Prevention (U.S.)Cessation of life Chronic Clinic Clinical Coculture Techniques Communicable Diseases Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Dangerousness Data Development Dose Drug Kinetics ESKAPE pathogens Engineering Enterobacter Enterococcus faecium Environment Epithelial Cells Foundations Generations Genes Genetic Polymorphism Goals Growth Health Health Care Costs Healthcare Hereditary Disease Hospitalization Host Defense Human In Vitro Individual Infection Investments Kinetics Klebsiella pneumoniae Lead Life Liver Dysfunction Lung Lung infections Maximum Tolerated Dose Medical Microbial Biofilms Minimum Inhibitory Concentration measurement Modeling Multi-Drug Resistance Mus Mutation Newly Diagnosed Outcome Pancreas Patients Persons Pharmaceutical Preparations Phase Positioning Attribute Property Pseudomonas aeruginosa Pulmonary Cystic Fibrosis Reporting Resistance Resistance development Respiratory System Safety Security Small Business Innovation Research Grant Staphylococcus aureus Structure Test Result Testing Therapeutic Toxic effect United States Virus Wild Type Mouse World Health Organization airway epithelium antibiotic resistant infections antimicrobial antimicrobial peptide antimicrobial resistant pathogen bacterial resistance base cathelicidin antimicrobial peptide combat cystic fibrosis mouse cystic fibrosis patients cytotoxicity design efficacy testing immunogenicity improved in vivo innovation lead optimization microbial mortality multi-drug resistant pathogen multidisciplinary multidrug-resistant Pseudomonas aeruginosa next generation novel novel therapeutics pathogen prevent resistant strain respiratory protein standard of care success synthetic peptide therapeutic candidate

项目摘要

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.

项目概要过去十年，美国和世界其他地区的细菌耐药性已达到惊人水平。抗菌素耐药 (AMR) 病原体细菌感染的增加导致医疗保健需求增加根据疾病控制中心的抗生素，成本和积极临床结果的下降。 2019年美国耐药性威胁报告（2019 AR Threats Report），超过280万种抗生素美国每年都会发生耐药感染，并导致超过 35,000 人因此死亡。迫切需要控制这些 AMR 病原体引起的感染，因为：(a) 需要住院治疗的感染者仍然很高；(b) 过度使用抗生素导致了其他多重耐药（MDR）菌株的持续出现。迫切需要开发具有广谱活性的新型抗菌化合物 AMR 细菌具有良好的耐受性，并且选择耐药菌株的倾向较低。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且重要的 MDR 病原体。 CDC 和世界卫生组织 (WHO) 高度重视。我们寻求开发我们的领先抗菌肽 CM-YPD1，它具有针对临床的广谱活性。分离 ESKAPE 病原体来治疗越来越多的耐多药感染患者。专注于开发 CM-YPD1 用于治疗囊性纤维化患者的慢性肺部感染。多学科团队汇集了学术和商业专业知识的独特组合，允许开发一种可用于治疗越来越多的危及生命的患者的药物耐多药细菌感染。