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：
10407645
负责人：
Stephanie Ann Fritz
金额：
$ 78.19万
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/10407645
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 Data 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 Lead 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 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 topical antiseptic 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.

项目摘要对抗抗生素耐药细菌的国家行动计划确定了关键的研究需要面对抗菌抗性的前进威胁。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预防疾病的策略。金黄色葡萄球菌在医疗保健和社区环境。金黄色葡萄球菌承认内源性感染的风险。先前的研究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，尽管尚不清楚皮肤和鼻菌群对金黄色葡萄球菌采集的影响。我们假设该功能 Comensal Microbiota可能会访问或提供针对金黄色葡萄球菌的敏感性或提供保护和随后感染的发展。此外，为了防止金黄色葡萄球菌获取和感染，局部抗菌药物的非殖民化经常用于医疗保健和社区环境。然而，广谱局部抗菌施用可能会破坏共生菌群，从而促进获得或富集多药耐药和/或潜在的致病性微生物。这个影响潜在的不利影响仍然被理解。在这个拟议的项目中，我们将分析> 13,000皮肤和鼻拭子的庞大而无与伦比的生物座从特征良好的476名参与者组成的人群中纵向收集了24个月的样本，包括99例耐甲氧西林链球菌皮肤感染及其家庭接触的儿科患者所有这些人都有获得金黄色葡萄球菌获取和感染的高风险。在12个月内收集样品纵向采样（自然历史阶段），然后是随机的5天非殖民化干预措施局部抗菌施用，然后进行纵向采样12个月（殖民后化后化我们将执行宏基因组shot弹枪测序（在物种上启用分类并应变级别），在金黄色葡萄球菌的背景下纵向表征皮肤和鼻微生物群落定植和疾病。我们将比较与易感性相关的微生物社区特征或与不同表型结果之间的家庭接触之间对金黄色葡萄球菌采集的抵抗力（例如，殖民和感染），并将这些数据与详细的流行病学数据整合在一起，以预测个人获得金黄色葡萄球菌定植和/或发展症状感染的风险。我们将量化更改局部抗菌应用后的微生物社区结构，并将这种破坏与随后获得金黄色葡萄球菌和其他病原体的持久性和持久性。最后，我们将采用创新靶向序列捕获以量化抗菌素抗性（抗抗菌抗性）（“抵抗”）的遗传决定剂非殖民化前后收集的样品。这项研究产生的基本知识将优化金黄色葡萄球菌定植和感染及其针对易感人的预防策略。