Synergistic Drug Strategies Against Pseudomonas Aeruginosa Biofilms

针对铜绿假单胞菌生物膜的协同药物策略

基本信息

批准号：
8443320
负责人：
Jennifer Fiegel
金额：
$ 18.41万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-15 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8443320
关键词：
Acids Acquired Immunodeficiency Syndrome Acute Aerosols Affect Agar Animal Model Antibiotic Therapy Antibiotics Antimicrobial Resistance Area Azithromycin Bacteria Bacteriology Biological Assay Cessation of life Chelating Agents Chronic Clinical Combined Antibiotics Combined Modality Therapy Cystic Fibrosis Data Data Analyses Development Disease Drug Combinations Drug Compounding Drug Delivery Systems Effectiveness Environment Experimental Designs Food Goals Histopathology Human Immunocompromised Host In Vitro Individual Infection Inflammation Knowledge Laboratories Liquid substance Lung Mechanical ventilation Microbial Biofilms Mission Modeling Mucous body substance Mus Neutropenia Nutrient Oral Outcome Patients Pharmaceutical Preparations Physicians Pseudomonas aeruginosa Public Health Quality of life Research Resources Respiratory Tract Infections Saline Scientist Sodium Chloride Solutions Source Staging Swimming Symptoms System Testing Time Tobramycin aggressive therapy base burden of illness chemotherapy combat experience improved in vivo innovation killings mortality mucoid novel pathogen patient population public health relevance quorum sensing research study respiratory treatment strategy

项目摘要

DESCRIPTION (provided by applicant): There is a fundamental gap in understanding the extent to which treatment of bacterial biofilms with combinations of drug compounds may synergistically kill the biofilm colonies. Continued existence of this gap represents an important problem because, until it is filled, the development of co-therapy systems for clinical use in chronic infections will be delayed. The long term goal of this research is to develop novel and effective inhalable strategies for the treatment of respiratory infections. The objective in this application is to identify compounds that, when delivered in combination, more effectively eradicate Pseudomonas aeruginosa biofilms. Our central hypothesis is that delivery of selected dispersion compounds will increase the sensitivity of P. aeruginosa to antibiotic treatment, resulting in improved outcomes in a murine model. This hypothesis has been formulated on the basis of preliminary data produced in the applicants' laboratories. Once it is known which combinations of compounds can synergistically enhance biofilm killing in vitro and in vivo, new treatment strategies based on these compounds can be clinically developed. The proposed research is innovative because it focuses on enhancing the effectiveness of traditional antibiotics with the use of dispersion compounds that target disruption of the biofilm. The proposed research is significant because it is expected to provide knowledge needed for the clinical development of inhalable co-delivery aerosols for the treatment of bacterial biofilms.

描述（由申请人提供）：对于用药物化合物的组合处理细菌生物膜可以协同杀死生物膜菌落的程度的理解存在根本性的差距。这一差距的持续存在是一个重要问题，因为在填补这一差距之前，用于慢性感染临床的联合治疗系统的开发将被推迟。这项研究的长期目标是开发治疗呼吸道感染的新颖有效的吸入策略。本申请的目的是确定组合使用时能够更有效地根除铜绿假单胞菌生物膜的化合物。我们的中心假设是，输送选定的分散化合物将增加铜绿假单胞菌对抗生素治疗的敏感性，从而改善小鼠模型的结果。该假设是根据申请人实验室产生的初步数据制定的。一旦知道哪些化合物组合可以协同增强体外和体内生物膜杀灭作用，就可以在临床上开发基于这些化合物的新治疗策略。拟议的研究具有创新性，因为它的重点是通过使用针对生物膜破坏的分散化合物来增强传统抗生素的有效性。拟议的研究意义重大，因为它有望为治疗细菌生物膜的可吸入共递送气雾剂的临床开发提供所需的知识。