Temporal dynamics of MDRO eradication after FMT
FMT 后 MDRO 根除的时间动态
基本信息
- 批准号:10598519
- 负责人:
- 金额:$ 19.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:16S ribosomal RNA sequencingAR geneActive SitesAddressAnaerobic BacteriaAntibioticsAntimicrobial ResistanceBacteriaBacterial Antibiotic ResistanceBacterial Drug ResistanceBacteriophagesBenchmarkingBiomedical ResearchCenters for Disease Control and Prevention (U.S.)Cessation of lifeClinicalClinical ResearchClinical TrialsClostridium difficileCollaborationsCollectionComplementControl GroupsDataData ScienceData ScientistDevelopmentDiseaseDrynessEducational workshopEnterobacteriaceaeEnvironmentExtended-spectrum β-lactamaseFecesFrequenciesFundingFutureGenesGoalsInfectionInstitutionIntestinesInvestigationK-Series Research Career ProgramsKidney TransplantationLinkMentorsMentorshipMetabolic PathwayMetabolismMetagenomicsMethodsMicrobiologyMorbidity - disease rateMulti-Drug ResistanceOrganismParticipantPatientsPersonsPharmaceutical PreparationsPrevalenceProcessPublic HealthPythonsRandomizedRandomized Controlled Clinical TrialsRecurrenceRefractoryResearchResourcesRiskSafetySamplingTechniquesTestingTherapeuticTimeTrainingTranslatingTransplant RecipientsUnited StatesViralVirulenceVirusWorld Health Organizationantimicrobial peptideantimicrobial resistant infectionapprenticeshipbacteriocincarbapenem-resistant Enterobacteriaceaecareercareer developmentclinical applicationcolonization resistancedesigndrug developmenteffective therapyfecal transplantationgenome sequencingglobal healthgut colonizationgut microbiotaimprovedinfection riskknowledge basemicrobialmicrobiomemortalitymulti-drug resistant pathogennephrotoxicitynext generation sequencingnoveloperational taxonomic unitspre-clinicalprogramspublic health interventionresistance genetherapeutic developmenttoolviromevirulence genewhole genome
项目摘要
PROJECT SUMMARY
The World Health Organization and U.S. Centers for Disease Control and Prevention have designated
antimicrobial resistance a major threat to Global Health with over 23,000 annual deaths related to antimicrobial
resistant infections in the U.S. alone. However, the drug pipeline to develop new antibiotics is dry. Small
studies support the safety and efficacy of fecal microbiota transplantation (FMT) to eliminate intestinal
colonization with antibacterial resistant organisms but its mechanisms are not well understood. We will
leverage patient-linked samples from a clinical trial PREMIX (NCT02922816) to test our overarching
hypothesis that anaerobic bacteria, viruses, and their gene-predicted functions are causally associated with
decreased MDRO colonization after FMT. The Specific Aims of this proposal include: Aim 1: Use the clinical
gold standard of bacterial culture to estimate efficacy of FMT in MDRO eradication. Aim 2A: Establish a novel
metagenomic analytic pipeline (MAP) to quantify abundance of bacterial and viral taxa, AR, virulence, and
colonization resistance genes. Aim 2B: Use 16S rRNA sequencing to estimate temporal dynamics of difficult to
culture bacterial taxa in FMT vs controls. Aim 2C: Use metagenomic whole-genome sequencing and the MAP
to estimate temporal dynamics of AR, virulence, and colonization resistance genes in FMT vs controls. Aim 3:
Use environmental virome NGS techniques to test the association of viral (including bacteriophage) taxa with
abundance of MDRO after FMT. We expect that completion of these aims and related training will lead to
clinically applicable preliminary data and next steps in translational microbial therapeutic development for
MDRO colonization. My long-term career goal is to become a collaborative leader in ID microbiome data
science focusing on: 1) mechanisms of microbial therapeutics such as FMT in reducing colonization with multi-
drug resistant organisms (MDRO), and 2) translating these findings into clinical and public health interventions
to reduce MDRO colonization and infection. Emory and Georgia Tech are ideal and highly-collaborative
research environments, which are both national leaders in biomedical research. Both institutions provide rich
resources to complete the described aims and progress in career development to become an independent
translational ID microbiome data scientist. In addition, Emory is an active site of microbial therapeutic
investigation with 7 clinical trials of microbial therapeutics and a clinical FMT program that has completed over
300 treatments for refractory Clostridioides difficile.
项目概要
世界卫生组织和美国疾病控制与预防中心已指定
抗菌药物耐药性是全球健康的主要威胁,每年有超过 23,000 人因抗菌药物死亡
仅在美国就有耐药性感染。然而,开发新抗生素的药物渠道却很枯竭。小的
研究支持粪便微生物群移植(FMT)消除肠道疾病的安全性和有效性
细菌耐药性微生物定植,但其机制尚不清楚。我们将
利用来自临床试验 PREMIX (NCT02922816) 的患者相关样本来测试我们的总体
假设厌氧细菌、病毒及其基因预测的功能与
FMT 后 MDRO 定植减少。该提案的具体目标包括: 目标 1:使用临床
评估 FMT 根除 MDRO 功效的细菌培养金标准。目标 2A:创作一部小说
宏基因组分析流程 (MAP),用于量化细菌和病毒类群的丰度、AR、毒力和
定植抗性基因。目标 2B:使用 16S rRNA 测序来估计难以预测的时间动态
FMT 与对照中培养细菌分类群。目标 2C:使用宏基因组全基因组测序和 MAP
评估 FMT 与对照中 AR、毒力和定植抗性基因的时间动态。目标 3:
使用环境病毒组 NGS 技术来测试病毒(包括噬菌体)分类群与
FMT 后 MDRO 丰度。我们期望完成这些目标和相关培训将导致
临床适用的初步数据和转化微生物治疗开发的后续步骤
MDRO定植。我的长期职业目标是成为 ID 微生物组数据领域的协作领导者
科学重点关注:1)微生物疗法(例如 FMT)减少多种微生物定植的机制
耐药微生物 (MDRO),以及 2) 将这些发现转化为临床和公共卫生干预措施
减少多重耐药菌定植和感染。埃默里大学和佐治亚理工学院是理想且高度合作的大学
研究环境,在生物医学研究方面均处于国家领先地位。两个机构都提供了丰富的
资源来完成所描述的目标并在职业发展中取得进展,成为独立的
转化 ID 微生物组数据科学家。此外,埃默里大学还是微生物治疗的活跃场所
7 项微生物疗法临床试验和已完成超过 10 项临床 FMT 项目的调查
治疗难治性艰难梭菌 300 次。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis.
- DOI:10.1016/j.cgh.2020.06.051
- 发表时间:2021-08
- 期刊:
- 影响因子:0
- 作者:Cheng YW;Alhaffar D;Saha S;Khanna S;Bohm M;Phelps E;Ghabril M;Orman E;Sashidhar S;Rogers N;Xu H;Khoruts A;Vaughn B;Kao D;Wong K;Cammarota G;Ianiro G;Dhere T;Kraft CS;Mehta N;Woodworth MH;Allegretti JR;Nativ L;Marcus J;El-Nachef N;Fischer M
- 通讯作者:Fischer M
mSphere of Influence: Microbiome-Associated Phenotypes Are Modifiable.
影响范围:微生物组相关表型是可修改的。
- DOI:10.1128/msphere.00508-20
- 发表时间:2020
- 期刊:
- 影响因子:4.8
- 作者:Woodworth,MichaelH
- 通讯作者:Woodworth,MichaelH
Critical Care Management of the Patient with Clostridioides difficile.
- DOI:10.1097/ccm.0000000000004739
- 发表时间:2021-01-01
- 期刊:
- 影响因子:8.8
- 作者:Adelman MW;Woodworth MH;Shaffer VO;Martin GS;Kraft CS
- 通讯作者:Kraft CS
Haemophagocytic lymphohistiocytosis associated with bartonella peliosis hepatis following kidney transplantation in a patient with HIV.
HIV 患者肾移植后与肝紫癜性巴尔通体相关的噬血细胞淋巴组织细胞增多症。
- DOI:10.1016/s1473-3099(22)00276-6
- 发表时间:2022-10
- 期刊:
- 影响因子:56.3
- 作者:Steed, Danielle;Collins, Jeffrey;Farris, Alton B.;Guarner, Jeannette;Yarar, Dilek;Friedman-Moraco, Rachel;Doane, Tristan;Pouch, Stephanie;Lyon, G. Marshall, III;Woodworth, Michael H.
- 通讯作者:Woodworth, Michael H.
Changes in treatment of community-onset Clostridioides difficile infection after release of updated guidelines, Atlanta, Georgia, 2018.
- DOI:10.1016/j.anaerobe.2021.102364
- 发表时间:2021-08
- 期刊:
- 影响因子:2.3
- 作者:Adelman MW;Goodenough D;Sefton S;Mackey C;Thomas S;Fridkin SK;Woodworth MH
- 通讯作者:Woodworth MH
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{{ truncateString('Michael Holmes Woodworth', 18)}}的其他基金
Temporal dynamics of MDRO eradication after FMT
FMT 后 MDRO 根除的时间动态
- 批准号:
10378130 - 财政年份:2019
- 资助金额:
$ 19.15万 - 项目类别:
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