Improving diagnosis of post-traumatic sepsis using plasma microbial DNA sequencing
利用血浆微生物 DNA 测序改善创伤后脓毒症的诊断
基本信息
- 批准号:10572825
- 负责人:
- 金额:$ 19.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-01-01 至 2027-12-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAntibioticsAntimicrobial ResistanceBacterial DNABioinformaticsBiological AssayBiological MarkersBloodBlood specimenCessation of lifeClinicalClinical ManagementClinical TrialsCommunicable DiseasesCommunitiesComputing MethodologiesDNADNA sequencingDataData AnalysesDedicationsDeteriorationDevelopmentDevelopment PlansDiagnosisDiagnosticDiagnostic testsDisciplineEarly DiagnosisEarly identificationEmergency SituationEtiologyGenomicsHospitalizationHospitalsHourIndividualInfectionInflammationInflammatory ResponseInjuryIntensive Care UnitsJudgmentLaboratoriesLifeLiteratureMeasuresMedicalMentorshipMicrobiologyMonitorMultiple Organ FailureOperative Surgical ProceduresOrganismOutcomePathogen detectionPatient AdmissionPatientsPhysiciansPhysiologicalPlasmaResearchSamplingScientistSepsisSeptic ShockSourceSurgeonTestingTimeTrainingTranslational ResearchTraumaTrauma patientTraumatic injuryUniversitiesWisconsinWithholding TreatmentWorkWritingantimicrobialcareer developmentcell free DNAclinically relevantdiagnostic accuracyearly detection biomarkersexperiencegenome sequencinggenomic datahealthy volunteerimprovedimproved outcomeindividualized medicinemetagenomic sequencingmicrobialmicrobial genomicsmortalitypathogenprofessorprospectiveradiological imagingrapid diagnosisresponseresponse to injurystandard of caresystemic inflammatory responsetissue injurytrauma surgerytreatment responsewhole genome
项目摘要
PROJECT SUMMARY/ABTRACT
This proposal presents a five-year research career development plan focused on improving diagnosis of
post-traumatic sepsis using microbial DNA sequencing in plasma. I am an Assistant Professor of Surgery at
the University of Wisconsin-Madison, with previous clinical and research experience in trauma surgery, patient-
centric predictors of sepsis, and lab-based genomic analyses of plasma in patients with sepsis. I have
assembled an outstanding mentorship team with expertise in infectious disease, cell-free DNA, genomic data
analysis, and bioinformatics. The proposed training will enhance my development across the disciplines of
translational research, laboratory and computational methods in genomics, and scientific writing. This will
enable me to transition to research independence as a surgeon-scientist dedicated to improving outcomes for
trauma patients with sepsis by developing better diagnostic tests based on microbial genomics.
Sepsis is a life-threatening condition, estimated to cause one-fifth of all deaths worldwide. Approximately
25% of trauma patients develop sepsis during their hospital course and more than 20% of such patients die
during the same hospitalization. Sepsis, if not recognized and treated early, may evolve into septic shock and
multiple organ failure. Thus, the treatment of sepsis emphasizes timely initiation of antibiotics and source
control in surgery/trauma patients. However, the diagnosis of sepsis in patients with traumatic injury is
complicated because systemic inflammatory response to injury mimics sepsis. In the current paradigm,
confirmation of sepsis is based on clinical signs, laboratory and radiographic findings, and medical scores
which are usually obtained after sepsis onset. There are approximately 200 biomarkers of sepsis described in
literature but nearly all such biomarkers rely on measuring inflammatory response, which is confounded in
patients with trauma. Recent studies, including my preliminary work, have shown that metagenomic
sequencing of plasma DNA can rapidly identify pathogens in patients with clinical suspicion of sepsis but these
assays have not been investigated in trauma patients. To address this gap, I propose to develop and evaluate
a metagenomic sequencing-based assay for analysis of microbial DNA shed into the blood. My central
hypothesis is that quantitative analysis of microbial DNA levels in trauma patients can predict sepsis, rapidly
identify the causative organism of sepsis, and help decrease the duration of antimicrobial treatment. Using
prospectively collected plasma samples from trauma patients, I propose the following aims: 1) To determine if
an increase in circulating microbial DNA levels is predictive of sepsis in trauma patients, 2) To assess
concordance between causative organism identified using standard-of-care microbiology and detection of
pathogen-specific DNA in plasma, and 3) To evaluate circulating microbial DNA levels in plasma as a
biomarker for monitoring antimicrobial response.
项目总结/ ABTRACT
项目成果
期刊论文数量(0)
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