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: 10614690
• 负责人: Cesar Augusto Arias
• 金额: $ 241.15万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10614690
• 关键词: Affect; Antibiotic Resistance; Antimicrobial Resistance; Bacteria; Clinical; Clostridium difficile; Collaborations; Communities; Community Hospitals; Critical Illness; Data; Development; Diagnosis; Disease; Extended-spectrum β-lactamase; Functional disorder; Gastrointestinal tract structure; Genome; Genomics; Goals; Hospitals; Immunocompromised Host; Individual; Infection; Intensive Care Units; Intervention; Intestines; Investigation; Knowledge; Longitudinal Studies; Mediating; Medical center; Metagenomics; Multi-Drug Resistance; Multiple Bacterial Drug Resistance; Names; Nature; Organism; Patients; Play; Population; Positioning Attribute; Predisposition; Prevention; Preventive; Prospective cohort; Recording of previous events; Resistance; Resources; Ribosomal RNA; Risk; Role; Sampling; Signal Transduction; Site; Stem cell transplant; System; Texas; Therapeutic; Transplant Recipients; United Nations; Vancomycin resistant enterococcus; antimicrobial; base; carbapenem resistance; carbapenem-resistant Enterobacteriaceae; clinical epidemiology; clinical risk; cohort; combat; commensal microbes; genomic epidemiology; gut colonization; gut microbiota; high risk; host microbiome; host microbiota; member; metaproteomics; microbial; microbiome; microbiome composition; microbiome research; microbiota; multi-drug resistant pathogen; novel; novel diagnostics; pathobiont; pathogen; patient population; patient subsets; programs; public health priorities; public health relevance; stool sample; tool; trait

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

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: Antibiotics (Basel, Switzerland)
• 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: Antimicrobial agents and chemotherapy
• 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: Antimicrobial agents and chemotherapy
• 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: Open forum infectious diseases
• 影响因子: 4.2

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: GigaScience
• 影响因子: 9.2
• 作者: Fu Y;Mahmoud M;Muraliraman VV;Sedlazeck FJ;Treangen TJ
• 通讯作者: Treangen TJ