Microbial Community Disruption Following Topical Antimicrobial Application in Staphylococcus aureus-Affected Households

受金黄色葡萄球菌影响的家庭局部使用抗菌药物后微生物群落的破坏

基本信息

批准号：
10609037
负责人：
Stephanie Ann Fritz
金额：
$ 77.96万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-19 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10609037
关键词：
Address Adult Adverse effects Affect Antibiotic Resistance Antibiotics Antimicrobial Resistance Bacterial Antibiotic Resistance Biometry Characteristics Childhood Classification Clinical Clinical Microbiology Combating Antibiotic Resistant Bacteria Communities Computational Biology Coupled Detection Development Disease Effectiveness Epidemiologic Factors Epidemiology Exposure to Genes Genetic Determinism Hospitals Household Human Incidence Individual Infection Infectious Disease Epidemiology Infectious Skin Diseases Intensive Care Units Intervention Knowledge Local Anti-Infective Agents Measures Metabolic Metadata Metagenomics Morbidity - disease rate Multi-Drug Resistance Natural History Nature Nose Outcome Outpatients Participant Pathogenicity Patients Phase Phenotype Plasmids Population Predisposition Prevention strategy Preventive measure Public Health Randomized Regimen Research Resistance Risk Sampling Seminal Shotgun Sequencing Skin Staphylococcus aureus Staphylococcus aureus infection Structure Testing Topical Antibiotic Topical application antimicrobial bacterial community biobank cohort commensal microbes community setting comparison control data integration disorder prevention epidemiologic data health care settings high risk innovation methicillin resistant Staphylococcus aureus microbial community microbial genomics microbiota microorganism mortality multi-drug resistant pathogen multidimensional data multidisciplinary nasal microbiota nasal swab pathogen pathogenic microbe pediatric patients post intervention prevent repository resistance gene skin microbiota transmission process treatment strategy ward

项目摘要

PROJECT SUMMARY The National Action Plan for Combating Antibiotic-Resistant Bacteria identified critical research needs to confront the advancing threat of antimicrobial resistance. These include understanding the nature of microbial communities, determining the effects of antibiotics on these communities, and harnessing these communities to develop strategies for disease prevention. Staphylococcus aureus causes significant morbidity and mortality in healthcare and community settings. S. aureus carriage confers risk for endogenous infection. Previous studies investigated clinical and epidemiological factors associated with S. aureus colonization and infection, although the influence of the skin and nasal microbiota on S. aureus acquisition is unclear. We hypothesize that features of the commensal microbiota may confer susceptibility to, or provide protection against, S. aureus acquisition and development of subsequent infection. Further, in an effort to prevent S. aureus acquisition and infection, decolonization with topical antimicrobials is frequently employed in healthcare and community settings. However, broad-spectrum topical antimicrobial application may disrupt commensal microbiota, thereby promoting the acquisition or enrichment of multidrug-resistant and/or potentially pathogenic microorganisms. The impact of this potential adverse effect remains understudied. In this proposed project, we will analyze a vast and unmatched biorepository of >13,000 skin and nasal swab samples that were longitudinally collected over 24 months from a well-characterized cohort of 476 participants, including 99 pediatric patients with methicillin-resistant S. aureus skin infections and their household contacts, all of whom are at high risk for S. aureus acquisition and infection. The samples were collected during 12 months of longitudinal samplings (the natural history phase) followed by a randomized, 5-day decolonization intervention with topical antimicrobial application, and subsequent longitudinal sampling for 12 months (post-decolonization phase). We will perform metagenomic shotgun sequencing (enabling classification at the species and strain levels), to longitudinally characterize skin and nasal microbial communities in the context of S. aureus colonization and disease. We will compare microbial community features associated with susceptibility or resistance to S. aureus acquisition between household contacts with different phenotypic outcomes (e.g., colonization and infection), and integrate these data with detailed epidemiological data to predict individuals at risk for acquiring S. aureus colonization and/or developing symptomatic infection. We will quantify changes in microbial community structures following topical antimicrobial application, and correlate this disruption with subsequent acquisition and persistence of S. aureus and other pathogens. Finally, we will employ innovative targeted sequence capture to quantify genetic determinants of antimicrobial resistance (the “resistome”) in samples collected before and after decolonization. The essential knowledge generated by this study will optimize preventive strategies for S. aureus colonization and infection and their targeting to susceptible individuals.

项目概要国家抗击抗生素耐药性细菌行动计划确定了关键研究需求应对抗菌素耐药性的威胁，其中包括了解微生物的性质。社区，确定抗生素对这些社区的影响，并利用这些社区制定疾病预防策略。金黄色葡萄球菌导致显着的发病率和死亡率。先前的研究表明，医疗保健和社区环境中金黄色葡萄球菌携带会带来内源性感染的风险。研究了与金黄色葡萄球菌定植和感染相关的临床和流行病学因素，尽管皮肤和鼻腔微生物群对金黄色葡萄球菌感染的影响尚不清楚。共生微生物群的数量可能会赋予金黄色葡萄球菌易感性，或提供针对金黄色葡萄球菌感染的保护此外，为了防止金黄色葡萄球菌获得和感染，然而，在医疗保健和社区环境中经常采用外用抗菌药物进行去定植。广谱局部抗菌药物的应用可能会破坏共生微生物群，从而促进获得或富集多重耐药性和/或潜在致病微生物的影响。潜在的不利影响仍有待研究。在这个拟议的项目中，我们将分析一个巨大且无与伦比的生物样本库，其中包含超过 13,000 个皮肤和鼻拭子样本是在 24 个月内从 476 名参与者组成的特征明确的队列中纵向收集的，包括 99 名患有耐甲氧西林金黄色葡萄球菌皮肤感染的儿科患者及其家庭接触者，所有这些人都具有金黄色葡萄球菌感染和感染的高风险。样本是在 12 个月内收集的。纵向采样（自然历史阶段），然后进行随机、为期 5 天的非殖民化干预局部应用抗菌药物，随后进行 12 个月的纵向采样（去殖民化后）我们将进行宏基因组鸟枪法测序（实现物种和菌株的分类）。水平），纵向描述金黄色葡萄球菌背景下的皮肤和鼻腔微生物群落特征我们将比较与易感性或相关的微生物群落特征。具有不同表型结果的家庭接触者对金黄色葡萄球菌感染的抵抗力（例如，定植和感染），并将这些数据与详细的流行病学数据相结合，以预测个体我们将量化金黄色葡萄球菌定植和/或出现症状感染的风险。局部抗菌药物应用后的微生物群落结构，并将这种破坏与金黄色葡萄球菌和其他病原体的后续获取和持久性最后，我们将采用创新技术。靶向序列捕获以量化抗生素耐药性的遗传决定因素（“resistome”）去殖民化前后收集的样本将优化本研究产生的基本知识。金黄色葡萄球菌定植和感染的预防策略及其针对易感个体的预防策略。