Dynamics of Colonization and Infection by Multidrug-resistant Pathogens in Immunocompromised and Critically Ill Patients (DYNAMITE)
免疫功能低下和危重患者中多重耐药病原体定植和感染的动态 (DYNAMITE)
基本信息
- 批准号:10614690
- 负责人:
- 金额:$ 241.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-01 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAntibiotic ResistanceAntimicrobial ResistanceBacteriaClinicalClostridium difficileCollaborationsCommunitiesCommunity HospitalsCritical IllnessDataDevelopmentDiagnosisDiseaseExtended-spectrum β-lactamaseFunctional disorderGastrointestinal tract structureGenomeGenomicsGoalsHospitalsImmunocompromised HostIndividualInfectionIntensive Care UnitsInterventionIntestinesInvestigationKnowledgeLongitudinal StudiesMediatingMedical centerMetagenomicsMulti-Drug ResistanceMultiple Bacterial Drug ResistanceNamesNatureOrganismPatientsPlayPopulationPositioning AttributePredispositionPreventionPreventiveProspective cohortRecording of previous eventsResistanceResourcesRibosomal RNARiskRoleSamplingSignal TransductionSiteStem cell transplantSystemTexasTherapeuticTransplant RecipientsUnited NationsVancomycin resistant enterococcusantimicrobialbasecarbapenem resistancecarbapenem-resistant Enterobacteriaceaeclinical epidemiologyclinical riskcohortcombatcommensal microbesgenomic epidemiologygut colonizationgut microbiotahigh riskhost microbiomehost microbiotamembermetaproteomicsmicrobialmicrobiomemicrobiome compositionmicrobiome researchmicrobiotamulti-drug resistant pathogennovelnovel diagnosticspathobiontpathogenpatient populationpatient subsetsprogramspublic health prioritiespublic health relevancestool sampletooltrait
项目摘要
ABSTRACT - OVERALL
Dynamics of Colonization and Infection by Multidrug-Resistant Pathogens in Immunocompromised
and Critically Ill Patients (DYNAMITE) Program.
Antimicrobial resistance (AMR) in community and hospital-associated pathogens has been named one of the
most pressing public health priorities by the United Nations. Among the most relevant multidrug-resistant
(MDR) bacteria, vancomycin-resistant enterococci (VRE), extended spectrum β-lactamase
producing/carbapenem-resistant Enterobacteriaceae (ESBL-E/CRE) and Clostridiodes difficile are
considered high priority inasmuch as these organisms commonly infect severely ill and immunocompromised
patients, and there is a paucity of therapeutic options to treat infections caused by these bacteria. For each of
these key pathogens, the intestines are the site of initial colonization and, under the influence of broad-
spectrum antimicrobial therapies, these organisms can “dominate” the gastrointestinal tract increasing the risk
of clinical disease. Importantly, it is becoming progressively clear that colonization of the intestines by either
VRE, ESBL-E/CRE, or C. difficile is markedly associated with subsequent colonization by other members of
this group, but whether pathogen-to-pathogen signaling plays a role is not known. Further, data generated from
microbiome-based studies to date has not allowed for clinically impactful interventions due to the imprecise
identification of high-risk patients and it is currently unclear why only a subset of patients, under apparently
similar conditions, develop colonization/disease. Our overarching hypothesis is that patient susceptibility to
gut-derived nosocomial colonization and subsequent infection is critically dependent on functional microbiota-
pathogen interactions that can be detected via a holistic combination of pathogen, host, and commensal
microbiota analyses. The DYNAMITE program (Dynamics of Colonization and Infection by Multidrug-Resistant
Pathogens in Immunocompromised and Critically Ill Patients) seeks to fill these important gaps in knowledge.
Indeed, we have identified keystone microbiota features that are broadly protective against gut-derived
pathogens via previously unappreciated antimicrobial mechanisms suggesting that lack of such organisms may
be a critical factor in determining pathogen colonization and infection. The aims of the program are, i) dissect
the main microbial, clinical and antimicrobial resistance determinants that impact colonization and infection by
VRE, ESBL-E/CRE and C. difficile, ii) evaluate the role of the commensal microbiota in VRE, ESBL-E/CRE
and C. difficile colonization, and iii) define the functional aspects of keystone microbiota and mechanisms of
protection against colonization/infection. Our strong history of multi-institutional collaboration on AMR and
microbiome science with centralized state-of-the art facilities, administrative resources, and access to two
major cohorts of critically ill and immunocompromised patients in the Texas Medical Center, place our team in
a unique and ideal position to achieve the goals. We expect that the findings of our high impact,
complementary projects will provide critical platforms for the development of novel diagnostic, preventive, and
therapeutic approaches to combat gut-derived AMR organisms affecting critically ill individuals.
摘要-总体
免疫功能低下患者多药耐药病原体的定植和感染动态
重症患者(Critically Ill Patients,简称CRIITE)
社区和医院相关病原体的抗菌药物耐药性(AMR)已被命名为
联合国最紧迫的公共卫生优先事项。在最相关的多药耐药
(MDR)细菌,万古霉素耐药肠球菌,超广谱β-内酰胺酶
产/碳青霉烯耐药肠杆菌科(ESBL-E/CRE)和艰难梭菌是
由于这些微生物通常感染严重疾病和免疫功能低下的人,
患者,并且缺乏治疗这些细菌引起的感染的治疗选择。中的每
这些关键的病原体,肠道是最初的殖民地,并在广泛的影响下,
如果使用广谱抗菌药物治疗,这些微生物可以“支配”胃肠道,增加风险
临床疾病。重要的是,越来越清楚的是,
VRE、ESBL-E/CRE或C.艰难梭菌与随后的其他成员的殖民化显著相关。
这一组,但是否病原体-病原体信号转导发挥作用是未知的。此外,从
迄今为止,基于微生物组的研究由于不精确,
目前尚不清楚为什么只有一部分患者,
类似的条件,发展殖民/疾病。我们的总体假设是,
肠道源性医院定植和随后的感染严重依赖于功能性微生物群-
病原体相互作用,可以通过病原体、宿主和寄生虫的整体组合来检测
微生物群分析。多药耐药菌的定殖和感染动力学(Dynamics of Colonization and Infection by Multidrug Resistant
免疫功能低下和危重病患者的病原体)试图填补这些重要的知识空白。
事实上,我们已经确定了主要的微生物群特征,这些特征广泛地保护了肠道源性疾病。
病原体通过以前未被认识到的抗菌机制,这表明缺乏这种微生物可能
是确定病原体定殖和感染的关键因素。该计划的目的是,i)剖析
影响定植和感染的主要微生物、临床和抗菌素耐药性决定因素,
VRE、ESBL-E/CRE和C.艰难梭菌,ii)评价肠道微生物群在VRE、ESBL-E/CRE中的作用
和C.艰难定植,和iii)定义关键微生物群的功能方面和
防止定植/感染。我们在AMR方面的多机构合作历史悠久,
微生物组科学与集中国家的最先进的设施,行政资源,并获得两个
德克萨斯州医疗中心的重症和免疫功能低下患者的主要队列,将我们的团队置于
实现目标的独特而理想的位置。我们希望我们的高影响力的发现,
互补项目将为开发新的诊断、预防和治疗方法提供关键平台。
治疗方法,以打击肠源性AMR生物体影响危重病人。
项目成果
期刊论文数量(68)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Evaluation of Bacteriophage-Antibiotic Combination Therapy for Biofilm-Embedded MDR Enterococcus faecium.
- DOI:10.3390/antibiotics11030392
- 发表时间:2022-03-15
- 期刊:
- 影响因子:0
- 作者:Lev K;Kunz Coyne AJ;Kebriaei R;Morrisette T;Stamper K;Holger DJ;Canfield GS;Duerkop BA;Arias CA;Rybak MJ
- 通讯作者:Rybak MJ
Efficacy of Omadacycline against Multidrug-Resistant Enterococcus faecium Strains in a Mouse Peritonitis Model.
奥马达环素在小鼠腹膜炎模型中对抗多重耐药屎肠球菌菌株的功效。
- DOI:10.1128/aac.00709-21
- 发表时间:2021
- 期刊:
- 影响因子:4.9
- 作者:Singh,KavindraV;Arias,CesarA;Murray,BarbaraE
- 通讯作者:Murray,BarbaraE
Multisite Detection of Tn1549-Mediated vanB Vancomycin Resistance in Multidrug-Resistant Enterococcus faecalis ST6 in Texas and Florida.
德克萨斯州和佛罗里达州多重耐药粪肠球菌 ST6 中 Tn1549 介导的 vanB 万古霉素耐药性的多位点检测。
- DOI:10.1128/aac.01284-22
- 发表时间:2023
- 期刊:
- 影响因子:4.9
- 作者:Simar,ShelbyR;Tran,TrucT;Rydell,KirstenB;Panesso,Diana;Contreras,GermanA;Munita,JoseM;Cifuentes,RenzoO;Abbo,LilianM;Sahasrabhojane,Pranoti;Dinh,AnQ;Axell-House,DierdreB;Savidge,Tor;Shelburne,SamuelA;Hanson,BlakeM;Ari
- 通讯作者:Ari
Clinical Impact of Ceftriaxone Resistance in Escherichia coli Bloodstream Infections: A Multicenter Prospective Cohort Study.
- DOI:10.1093/ofid/ofac572
- 发表时间:2022-11
- 期刊:
- 影响因子:4.2
- 作者:
- 通讯作者:
Population Genomics of emm4 Group A Streptococcus Reveals Progressive Replacement with a Hypervirulent Clone in North America.
- DOI:10.1128/msystems.00495-21
- 发表时间:2021-08-31
- 期刊:
- 影响因子:6.4
- 作者:DebRoy S;Sanson M;Shah B;Regmi S;Vega LA;Odo C;Sahasrabhojane P;McGeer A;Tyrrell GJ;Fittipaldi N;Shelburne SA;Flores AR
- 通讯作者:Flores AR
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Cesar Augusto Arias其他文献
Cesar Augusto Arias的其他文献
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{{ truncateString('Cesar Augusto Arias', 18)}}的其他基金
Clinical Impact of the Cefazolin Inoculum Effect
头孢唑啉接种效果的临床影响
- 批准号:
10735541 - 财政年份:2023
- 资助金额:
$ 241.15万 - 项目类别:
The LiaFSR system and antimicrobial peptide resistance in enterococci
LiaFSR 系统和肠球菌抗菌肽耐药性
- 批准号:
10553808 - 财政年份:2022
- 资助金额:
$ 241.15万 - 项目类别:
Dynamics of Colonization and Infection by Multidrug-resistant Pathogens in Immunocompromised and Critically Ill Patients (DYNAMITE)
免疫功能低下和危重患者中多重耐药病原体定植和感染的动态 (DYNAMITE)
- 批准号:
10226283 - 财政年份:2020
- 资助金额:
$ 241.15万 - 项目类别:
VENOUS: A translational study of enterococcal bacteremia
静脉:肠球菌菌血症的转化研究
- 批准号:
10624439 - 财政年份:2020
- 资助金额:
$ 241.15万 - 项目类别:
Project 1: Genomics of Pathobionts and Transition From Colonization to Infection
项目 1:病原体基因组学和从定植到感染的转变
- 批准号:
10226287 - 财政年份:2020
- 资助金额:
$ 241.15万 - 项目类别:
Dynamics of Colonization and Infection by Multidrug-resistant Pathogens in Immunocompromised and Critically Ill Patients (DYNAMITE)
免疫功能低下和危重患者中多重耐药病原体定植和感染的动态 (DYNAMITE)
- 批准号:
10024956 - 财政年份:2020
- 资助金额:
$ 241.15万 - 项目类别:
Project 1: Genomics of Pathobionts and Transition From Colonization to Infection
项目 1:病原体基因组学和从定植到感染的转变
- 批准号:
10614693 - 财政年份:2020
- 资助金额:
$ 241.15万 - 项目类别:
VENOUS: A translational study of enterococcal bacteremia
静脉:肠球菌菌血症的转化研究
- 批准号:
10593508 - 财政年份:2020
- 资助金额:
$ 241.15万 - 项目类别:
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