Rapid Identification of Neutropenic Patients at High Risk of CRE Bacteremia
快速识别 CRE 菌血症高风险中性粒细胞减少症患者
基本信息
- 批准号:8805387
- 负责人:
- 金额:$ 17.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-12-09 至 2019-11-30
- 项目状态:已结题
- 来源:
- 关键词:Acute leukemiaAdmission activityAnti-Bacterial AgentsAntibiotic ResistanceAntibiotic TherapyAntibiotic susceptibilityAntibioticsAreaAwardBacteremiaBacteriaBacterial InfectionsBiological AssayBiometryCarbapenemsCaringCenters for Disease Control and Prevention (U.S.)ClinicalClinical MicrobiologyClinical ResearchCodeCountryDataDetectionDevelopmentDiagnosisDiagnosticDiagnostic ProcedureEarly DiagnosisEnsureEnterobacteriaceaeEnterobacteriaceae InfectionsEnzymesEpidemiologic StudiesEpidemiologyFecesFeverFluoroquinolonesFosteringFoundationsGenesGeneticGoalsGram-Negative BacteriaHematologic NeoplasmsHematopoietic stem cellsHigh PrevalenceImmunocompromised HostIndividualInfectionInfectious Diseases ResearchInguinal regionInstitutionIntensive Care UnitsInvestigationKlebsiella pneumonia bacteriumKnowledgeLaboratoriesLactamsLeadLearningLeftMalignant NeoplasmsMaster&aposs DegreeMediatingMentorsMentorshipMolecularMolecular Diagnostic TechniquesMolecular EpidemiologyMolecular GeneticsMulti-Drug ResistanceNephrotoxicNeutropeniaNew York CityOutcomePatientsPhysiciansPolymyxin ResistancePolymyxinsPopulationPositioning AttributePrevalencePreventionPublic HealthReportingResearchResearch PersonnelResearch Project GrantsResistanceRiskRisk FactorsRoleScientistSpecimenStem cell transplantSurveillance ProgramSwabTestingTimeTrainingWritingantimicrobialantimicrobial drugbactericidebasecarbapenem-resistant Enterobacteriaceaecarbapenemasecareercareer developmentchemotherapycombatdesignexperiencegastrointestinalhigh riskkillingslecturesmeetingsmortalitynovelnovel strategiesoncologypathogenprogramspublic health relevancerapid detectionscreeningskillsskills trainingsuccesssymposiumtargeted treatmenttransmission process
项目摘要
DESCRIPTION (provided by applicant):
The candidate's career goal is to become a physician-scientist and direct an academic research program that focuses on the prevention, diagnosis, and treatment of infections caused by multidrug-resistant (MDR) bacteria in immunocompromised patients. The candidate has laid the foundation for achieving this goal by obtaining a Master's Degree in Clinical and Translational Investigation, gaining clinical expertise in caring for this population, and conducting clinical epidemiologic studies of MDR bacterial infections. However, in order for the candidate to achieve his career goal, he needs to enhance and expand upon his clinical research skills and acquire laboratory skills in clinical microbiology, molecular diagnostics, and molecular epidemiology.
A critical component of the candidate's training will be conducting the proposed research project on car- bapenem-resistant Enterobacteriaceae (CRE) in neutropenic patients with hematologic malignancies. CRE are MDR bacteria that are emerging worldwide and are classified by the CDC as an "urgent" antibiotic resistance threat. Neutropenic patients lack the ability to combat bacterial infections, and thus rely on immediate treatment with antibiotics that kill infecting bacteria. However, CRE are resistant to the antibiotic therapies that are recommended for fever in neutropenic patients, and it takes 2-4 days to identify CRE from cultures. The candidate found that 50-70% of neutropenic patients who develop bacteremia due to CRE died from these infections and there were long delays from the onset of infection until receipt of active antibiotics.
Polymyxins are the only antibiotics that are consistently active against CRE and are appropriate for the treatment of bacteremia. However, they are highly nephrotoxic and widespread use may lead to polymyxin resistance. The primary goals of this research project are to develop a strategy to rapidly identify neutropenic patients who are at high risk of CRE bacteremia, and thus should receive immediate therapy with a polymyxin when they develop fever, and to characterize the molecular epidemiology of CRE in this population. We hypothesize that detection of asymptomatic colonization with CRE portends a high risk of subsequent CRE bacteremia. The specific aims of this project are: 1) Identify risk factors for CRE acquisition and
CRE bacteremia in neutropenic patients; 2) Rapidly detect CRE colonization in neutropenic patients; and 3) Determine the genetic relatedness of CRE isolates in neutropenic patients. Fecal and inguinal/perianal swab specimens will be collected on admission and weekly from two groups of patients with prolonged neutropenia: those with acute leu- kemia who receive chemotherapy and those who receive a hematopoietic stem cell transplant. These patients will be followed to determine factors that lead to CRE acquisition and bacteremia. The candidate will also evaluate a novel molecular test to rapidly identify CRE colonization from swab specimens and genetically characterize colonizing and infecting CRE isolates. The study will be conducted in two large oncology centers that are uniquely located in an area that has the highest prevalence of CRE in the country.
This project proposes a five-year, multi-faceted training plan under the mentorship of Drs. Thomas Walsh and Barry Kreiswirth. Dr. Walsh has extensive expertise and experience in conducting clinical and translational infectious diseases research in immunocompromised patients and Dr. Kreiswirth has expertise in molecular diagnostics and molecular characterization of MDR bacteria. These mentors and a team of collaborators will meet regularly with the candidate throughout this award to ensure success of his research project and guide his career development. Through "hands-on" training in Dr. Kreiswirth's laboratory, the candidate will not only learn to perform relevant molecular typing and diagnostic techniques, but he will gain an understanding of the strengths and limitations of each of these tests. This mentored training will be supplemented by coursework in molecular genetics, molecular diagnostic methods, and biostatistics, guidance from a scientific advisory board of experts, attending local and national conferences, giving lectures and writing reviews on MDR bacteria, and serving on a national committee for antibiotic susceptibility testing.
The completion of the proposed project will lead to an understanding of the role of screening for gastrointestinal CRE colonization in identifying neutropenic patients at high risk for CRE bacteremia and the development of a test to rapidly identify CRE colonization. Furthermore, an understanding of the genetic relatedness of CRE isolates will inform the degree to which CRE are spread among oncology patients. After completion of this project, the candidate will be poised to submit a competitive R01 proposal of a multi-institutional trial of rapid detection of CRE colonization and targeted therapy, to determine whether this approach decreases mortality rates of neutropenic patients with CRE infections. The candidate's mentors and institution are committed to his success, both in completing this project, and ensuring that he achieves his career goal of becoming an independent clinical researcher in MDR bacterial infections.
描述(由申请人提供):
候选人的职业目标是成为一名医生-科学家,并指导一项学术研究计划,该计划侧重于预防,诊断和治疗免疫功能低下患者中由多药耐药(MDR)细菌引起的感染。候选人通过获得临床和转化研究硕士学位,获得护理这一人群的临床专业知识,并进行MDR细菌感染的临床流行病学研究,为实现这一目标奠定了基础。然而,为了让候选人实现他的职业目标,他需要提高和扩展他的临床研究技能,并获得临床微生物学、分子诊断学和分子流行病学方面的实验室技能。
候选人培训的一个关键组成部分将是进行拟议的研究项目,在血液系统恶性肿瘤患者中进行对碳青霉烯耐药的肠杆菌科(CRE)。CRE是世界范围内出现的MDR细菌,被CDC归类为“紧急”抗生素耐药性威胁。中性粒细胞减少症患者缺乏抵抗细菌感染的能力,因此依赖于立即使用杀死感染细菌的抗生素进行治疗。然而,CRE对推荐用于贫血患者发热的抗生素治疗具有抗性,并且需要2-4天才能从培养物中鉴定CRE。该候选人发现,50-70%因CRE而发生菌血症的血小板减少症患者死于这些感染,并且从感染开始到接受活性抗生素治疗有很长的延迟。
多粘菌素是唯一对CRE持续有效且适用于治疗菌血症的抗生素。然而,它们具有高度肾毒性,广泛使用可能导致多粘菌素耐药性。该研究项目的主要目标是制定一种策略,以快速识别处于CRE菌血症高风险的贫血患者,因此当他们出现发热时应立即接受多粘菌素治疗,并描述该人群中CRE的分子流行病学特征。我们假设检测到CRE无症状定植预示着随后发生CRE菌血症的高风险。本项目的具体目标是:1)识别CRE收购的风险因素,
CRE菌血症在血小板减少症患者; 2)快速检测CRE定植在血小板减少症患者;和3)确定CRE分离株在血小板减少症患者的遗传相关性。将在入院时和每周从两组长期中性粒细胞减少患者中采集粪便和腹股沟/肛周拭子样本:接受化疗的急性白血病患者和接受造血干细胞移植的患者。将对这些患者进行随访,以确定导致CRE获得和菌血症的因素。候选人还将评价一种新型分子检测方法,以快速鉴定拭子样本中的CRE定植,并对定植和感染CRE分离株进行遗传表征。该研究将在两个大型肿瘤中心进行,这两个中心位于该国CRE患病率最高的地区。
该项目提出了一个为期五年的,多方面的培训计划下的指导博士托马斯沃尔什和巴里Kreisperth。沃尔什博士在免疫功能低下患者中开展临床和转化感染性疾病研究方面拥有丰富的专业知识和经验,Kreisperth博士在MDR细菌的分子诊断和分子表征方面拥有专业知识。这些导师和合作者团队将在整个奖项期间定期与候选人会面,以确保他的研究项目取得成功并指导他的职业发展。通过在Kreisperth博士实验室的“动手”培训,候选人不仅将学习执行相关的分子分型和诊断技术,而且他将了解这些测试的优势和局限性。这种指导性培训将通过分子遗传学,分子诊断方法和生物统计学课程,专家科学咨询委员会的指导,参加地方和国家会议,就MDR细菌进行讲座和撰写评论,并在抗生素敏感性测试国家委员会任职。
拟议项目的完成将导致对胃肠道CRE定植筛查在识别CRE菌血症高风险的贫血患者中的作用的理解,并开发一种快速识别CRE定植的测试。此外,了解CRE分离株的遗传相关性将有助于了解CRE在肿瘤患者中传播的程度。完成该项目后,候选人将准备提交一份竞争性R 01提案,该提案涉及快速检测CRE定植和靶向治疗的多机构试验,以确定该方法是否降低CRE感染的贫血患者的死亡率。候选人的导师和机构致力于他的成功,无论是在完成这个项目,并确保他实现他的职业目标,成为一个独立的临床研究人员在MDR细菌感染。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Michael Joseph Satlin其他文献
Michael Joseph Satlin的其他文献
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{{ truncateString('Michael Joseph Satlin', 18)}}的其他基金
Screening for Resistant Enteric Bacteria to Personalize Infection Prevention Strategies in Neutropenic Patients
筛查耐药肠道细菌以制定中性粒细胞减少症患者的个性化感染预防策略
- 批准号:
10211106 - 财政年份:2020
- 资助金额:
$ 17.61万 - 项目类别:
Predicting Infections in Neutropenic Hosts Receiving Fluoroquinolone Prophylaxis
预测接受氟喹诺酮预防的中性粒细胞减少宿主的感染
- 批准号:
10206034 - 财政年份:2020
- 资助金额:
$ 17.61万 - 项目类别:
Predicting Infections in Neutropenic Hosts Receiving Fluoroquinolone Prophylaxis
预测接受氟喹诺酮预防的中性粒细胞减少宿主的感染
- 批准号:
10057041 - 财政年份:2020
- 资助金额:
$ 17.61万 - 项目类别:
Screening for Resistant Enteric Bacteria to Personalize Infection Prevention Strategies in Neutropenic Patients
筛查耐药肠道细菌以制定中性粒细胞减少症患者的个性化感染预防策略
- 批准号:
10439739 - 财政年份:2020
- 资助金额:
$ 17.61万 - 项目类别:
Screening for Resistant Enteric Bacteria to Personalize Infection Prevention Strategies in Neutropenic Patients
筛查耐药肠道细菌以制定中性粒细胞减少症患者的个性化感染预防策略
- 批准号:
10656238 - 财政年份:2020
- 资助金额:
$ 17.61万 - 项目类别:
Rapid Identification of Neutropenic Patients at High Risk of CRE Bacteremia
快速识别 CRE 菌血症高风险中性粒细胞减少症患者
- 批准号:
9392126 - 财政年份:2014
- 资助金额:
$ 17.61万 - 项目类别:
Rapid Identification of Neutropenic Patients at High Risk of CRE Bacteremia
快速识别 CRE 菌血症高风险中性粒细胞减少症患者
- 批准号:
8982215 - 财政年份:2014
- 资助金额:
$ 17.61万 - 项目类别:
Rapid Identification of Neutropenic Patients at High Risk of CRE Bacteremia
快速识别 CRE 菌血症高风险中性粒细胞减少症患者
- 批准号:
9173454 - 财政年份:2014
- 资助金额:
$ 17.61万 - 项目类别: