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

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

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
Vulcan: Improved long-read mapping and structural variant calling via dual-mode alignment.
  • DOI:
    10.1093/gigascience/giab063
  • 发表时间:
    2021-09-24
  • 期刊:
  • 影响因子:
    9.2
  • 作者:
    Fu Y;Mahmoud M;Muraliraman VV;Sedlazeck FJ;Treangen TJ
  • 通讯作者:
    Treangen TJ
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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:
P01 Administrative Core
P01 行政核心
  • 批准号:
    10614691
  • 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:
    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:
P01 Administrative Core
P01 行政核心
  • 批准号:
    10226284
  • 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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Ecological and Evolutionary Drivers of Antibiotic Resistance in Patients
患者抗生素耐药性的生态和进化驱动因素
  • 批准号:
    EP/Y031067/1
  • 财政年份:
    2024
  • 资助金额:
    $ 241.15万
  • 项目类别:
    Research Grant
Collaborative Research: Leveraging the interactions between carbon nanomaterials and DNA molecules for mitigating antibiotic resistance
合作研究:利用碳纳米材料和 DNA 分子之间的相互作用来减轻抗生素耐药性
  • 批准号:
    2307222
  • 财政年份:
    2024
  • 资助金额:
    $ 241.15万
  • 项目类别:
    Standard Grant
Molecular Epidemiology of Antibiotic Resistance in Clostridioides difficile
艰难梭菌抗生素耐药性的分子流行病学
  • 批准号:
    502587
  • 财政年份:
    2024
  • 资助金额:
    $ 241.15万
  • 项目类别:
Collaborative Research: Leveraging the interactions between carbon nanomaterials and DNA molecules for mitigating antibiotic resistance
合作研究:利用碳纳米材料和 DNA 分子之间的相互作用来减轻抗生素耐药性
  • 批准号:
    2307223
  • 财政年份:
    2024
  • 资助金额:
    $ 241.15万
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    Standard Grant
The roles of a universally conserved DNA-and RNA-binding domain in controlling MRSA virulence and antibiotic resistance
普遍保守的 DNA 和 RNA 结合域在控制 MRSA 毒力和抗生素耐药性中的作用
  • 批准号:
    MR/Y013131/1
  • 财政年份:
    2024
  • 资助金额:
    $ 241.15万
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Determining structural dynamics of membrane proteins in their native environment: focus on bacterial antibiotic resistance
确定膜蛋白在其天然环境中的结构动力学:关注细菌抗生素耐药性
  • 批准号:
    MR/X009580/1
  • 财政年份:
    2024
  • 资助金额:
    $ 241.15万
  • 项目类别:
    Fellowship
CAREER: Systems Microbiology and InterdiscipLinary Education for Halting Environmental Antibiotic Resistance Transmission (SMILE HEART)
职业:阻止环境抗生素耐药性传播的系统微生物学和跨学科教育(SMILE HEART)
  • 批准号:
    2340818
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    2024
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    Continuing Grant
Reinforcing the battle at the bacterial cell wall: Structure-guided characterization and inhibition of beta-lactam antibiotic resistance signalling mechanisms
加强细菌细胞壁的战斗:β-内酰胺抗生素耐药信号机制的结构引导表征和抑制
  • 批准号:
    480022
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The spread of antibiotic resistance in bacteria-plasmid networks
抗生素耐药性在细菌-质粒网络中的传播
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An RNA Nanosensor for the Diagnosis of Antibiotic Resistance in M. Tuberculosis
用于诊断结核分枝杆菌抗生素耐药性的 RNA 纳米传感器
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    10670613
  • 财政年份:
    2023
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    $ 241.15万
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