Targeting M. catarrhalis for Prevention and Treatment of Otitis Media

针对卡他莫拉菌预防和治疗中耳炎

• 批准号: 9265836
• 负责人: Anthony A Campagnari
• 金额: $ 39.8万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9265836
• 关键词: Active Immunization; Acute; Adherence; Adult; Antibiotic Resistance; Antibiotics; Area; Bacteria; Child; Chinchilla (genus); Chronic; Chronic Disease; Complex; Development; Disease; Environment; Goals; Health Care Costs; Healthcare Systems; Host Defense; Human; Immune system; Immunization; In Vitro; Incidence; Infant; Infection; International; Lead; Learning; Learning Skill; Life; Lung diseases; Metabolic Clearance Rate; Microbial Biofilms; Modeling; Modification; Mono-S; Moraxella (Branhamella) catarrhalis; Morbidity - disease rate; Mucous Membrane; Nontypable Haemophilus influenza; Office Visits; Operative Surgical Procedures; Otitis Media; PUVA Photochemotherapy; Physiological; Prevention; Published Comment; Recurrence; Recurrent disease; Reporting; Research; Research Project Grants; Resistance development; Risk; Role; School-Age Population; Sinusitis; Source; Speech Development; Streptococcus pneumoniae; Stress; Structure; Surface; Testing; Time; Treatment Protocols; Tympanostomy Tube Insertions; Vaccine Antigen; antimicrobial; bactericide; design; ear infection; effective therapy; experience; hearing impairment; in vivo; interest; middle ear; middle ear disorder; novel; novel therapeutic intervention; novel therapeutics; ototoxicity; pathogen; pediatrician; prevent; public health relevance; response; symposium; therapy design

 DESCRIPTION (provided by applicant): Moraxella catarrhalis, a Gram-negative bacterial mucosal pathogen, is a significant cause of middle ear infections (otitis media (OM)) and sinusitis in infants and children and an important source of exacerbations in adults with lung disease. Approximately 80% of all children under 3 will experience at least one episode of OM and many experience recurrent disease, which may result in hearing impairment and developmental/learning problems. OM is a significant source of direct and indirect health care costs and M. catarrhalis is responsible for 3 to 4 million pediatrician office visits annually. Chronic or recurrent OM is now considered a biofilm disease and there have been numerous reports demonstrating that M. catarrhalis forms biofilms in vivo. Biofilms on host surfaces promote adherence and persistence on mucosal tissues, provide protection from host defenses and antibiotics, and represent a primary source of chronic disease. Importantly, multiple studies have suggested that nasopharyngeal colonization with M. catarrhalis promotes subsequent persistent colonization with the two other major otopathogens Streptococcus pneumoniae and/or nontypeable Haemophilus influenzae (NTHI), resulting in a significantly increased risk of OM. The first goal of this proposed research project is to provide a thorough understanding of the contribution of M. catarrhalis to the stable and persistent colonization of the other otopathogens, which then potentiates the development of OM. Moreover, novel therapeutic approaches designed to eradicate planktonic and biofilm-associated bacteria from the middle ear would not only significantly decrease the constant use of antibiotics in young children, it would also decrease the associated morbidity and the need to perform surgeries for insertion of tympanostomy tubes. Thus, the second goal of this research plan is to adapt photodynamic therapy (PDT) into an efficacious, noninvasive treatment for both acute and chronic OM resulting from M. catarrhalis monospecies and polymicrobial biofilms.

 描述（由申请方提供）：卡他莫拉菌是一种革兰氏阴性细菌粘膜病原体，是婴儿和儿童中耳感染（中耳炎（OM））和鼻窦炎的重要原因，也是成人肺病加重的重要原因。大约80%的3岁以下儿童会经历至少一次OM发作，许多人会经历复发性疾病，这可能导致听力障碍和发育/学习问题。OM是直接和间接卫生保健费用的重要来源，M。卡他病每年导致300万至400万儿科医生就诊。慢性或复发性OM现在被认为是一种生物膜疾病，已有大量报道表明M。粘膜炎在体内形成生物膜。宿主表面的生物膜促进粘膜组织的粘附和持久性，提供免受宿主防御和抗生素的保护，并且是慢性疾病的主要来源。重要的是，多项研究表明，鼻咽M。卡他炎促进了随后另外两种主要耳病原体肺炎链球菌和/或不可分型的流感嗜血杆菌（NTHI）的持续定植，导致OM的风险显著增加。本研究计划的第一个目标是对M.卡他菌的稳定和持久的殖民地的其他耳病原体，然后加强OM的发展。此外，设计用于从中耳中根除鼓膜和生物膜相关细菌的新治疗方法不仅会显著减少幼儿持续使用抗生素，还将降低相关发病率和进行鼓膜造口管插入手术的需要。因此，本研究计划的第二个目标是使光动力疗法（PDT）成为一种有效的、非侵入性的治疗M引起的急性和慢性OM的方法。粘膜炎单菌种和多微生物生物膜。