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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.

项目总结