A fully integrated CentriFluidic system for direct bloodstream infection PID/AST
用于直接血流感染 PID/AST 的完全集成 CentriFluidic 系统
基本信息
- 批准号:9241943
- 负责人:
- 金额:$ 70.42万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-03-01 至 2020-02-29
- 项目状态:已结题
- 来源:
- 关键词:Acinetobacter baumanniiAcuteAddressAgreementAlgorithmic AnalysisAntibiotic ResistanceAntibioticsAntimicrobial susceptibilityAutomationBacteremiaBacteriaBacterial InfectionsBiological AssayBloodBlood CellsBlood specimenBlood-Borne PathogensCategoriesCentrifugationCharacteristicsClinicalClinical ManagementClinical SensitivityCulture TechniquesCytolysisDetectionDevicesDiagnosisDiagnosticDoseEnterobacterEscherichia coliEtiologyFeasibility StudiesGenotypeGoalsGravitationGuidelinesHospitalsHourHybridsIncidenceInfectionInflammatory ResponseIntestinesKlebsiella pneumonia bacteriumLibrariesLiquid substanceMass Spectrum AnalysisMinimum Inhibitory Concentration measurementModalityModificationMolecularMolecular AnalysisMonitorMulti-Drug ResistanceObservational StudyOrganismPatientsPhenotypePhysiciansPredispositionProceduresProcessProtocols documentationPseudomonas aeruginosaPublic HealthPublishingRecoveryRegimenReportingReproducibilityResearchResearch Project GrantsResistance profileSamplingSensitivity and SpecificitySepsisSeptic ShockSpecificitySpecimenSurvival RateSystemSystems IntegrationTechnologyTestingTimeUltracentrifugationUrinary tract infectionUrineWhole Bloodantimicrobialbaseblindclinically relevantevidence baseimprovedinnovationmeltingmicroorganismmortalitypathogenprecision medicineprospectiveprototypepublic health relevanceroutine Bacterial staintime usevalidation studies
项目摘要
DESCRIPTION (provided by applicant): There is a pressing need for a technology platform that can aid rapid AST profiling where MIC results are presented within a narrow time window of less than 3 hours. This acquires tremendous significance during bloodstream infections and rapid onset sepsis; the choice of antibiotics to surmount emergent antibiotic resistance and associated treatment modality in reduction of host inflammatory response is crucial for patient survival and recovery. Such a platform will finally usher in the "Precision medicine" approach for treating bacterial infections, whereby physicians are able to track antibiotic resistance profiles f pathogens in real time and adjust their antibiotic dosing regimens. It is highly unlikely that culture techniques can still be improved to significantly decrease total assay time (TAT). Therefore, this proposed system focuses on improving TAT by using molecular technologies for identification and characterization of microorganism susceptibility profile directly from fresh whole blood specimen of BSI patients. A first step forward, to decrease time-to-result, can be achieved by utilizing blood lysis centrifugation. Moreover, eliminating steps for obtaining clinica isolates will lead to the most optimal turnaround time. The overall hypotheses of this application
are that a CentriFluidic system can be used to perform a rapid PID and AST directly from whole blood without a need of blood cultivation or PCR amplification based on our successful clinical feasibility studies on urinary tract infection (UTI) directly from raw urine specimen with reproducible demonstration of polymicrobial infection detection and multi-drug resistance profiling. We developed, demonstrated and published an innovative molecular-based genotypic-phenotypic-hybrid approach for multiplexed bacterial PID and AST profiling with 100% clinical sensitivity, 96% clinical specificity, 98% minimum inhibitory concentration (MIC) and 97% categorical agreement in our most recent ongoing clinical feasibility study on 73 raw clinical urine samples. However, critical limitations of the current UTI platform exist, including inabilityto detect much lower abundance of bloodborne pathogens, the lack of system integration with an ultracentrifugation module and inability to cover all clinical relevant pathogens for BSIs. The main goal of this RO1 research project is to combine the advantages of lab automation, rapid molecular analysis, melt-curve signature analysis, genotypic pathogen quantification and phenotypic antibiotic conditions to dramatically improve the sensitivity and specificity of rapid, evidence-based PID and AST directly from patient blood samples. We propose to test the following hypotheses: Specific Aim 1: Transition the current electrochemical-based molecular analysis PID/AST platform technology from UTI to BSIs - Hypothesis: Lysis centrifugation can address the change of matrix effect from raw urine to whole blood samples and the issue of low abundant pathogen for BSIs. Specific Aim 2: Develop a dual-mode electrochemical-based dynamic hybridization analysis algorithm to expand the BSI PID/AST panel - Hypothesis: Dynamic hybridization analysis can be utilized to expand the species-specific identification of common and emerging pathogens for BSIs. Specific Aim 3: Prototype, validate and manufacture the CentriFluidic cartridge and system - Hypothesis: Ultracentrifugation (up to 50,000 g, gravitational force) can be incorporated into a multiplexed fluidic cartridge for a fully automated
BSIs PID/AST from whole blood samples in 3 hours. Specific Aim 4: Clinically validate the rapid BSI PID/AST CentriFluidic system according to CLSI guidelines - Hypothesis: Blood samples spiked with ATCC strain bacteria used in the analytical validation studies represent critical matrix characteristics of fresh whole blood samples from patients.
描述(由申请人提供):迫切需要一种能够帮助快速进行 AST 分析的技术平台,其中 MIC 结果在不到 3 小时的狭窄时间窗口内呈现,这在血流感染和快速发作的败血症期间具有巨大的意义;选择抗生素来克服新兴的抗生素耐药性以及减少宿主炎症反应的相关治疗方式对于患者的生存和康复至关重要,因此,这样的平台将最终迎来治疗细菌感染的“精准医学”方法。医生能够实时跟踪病原体的抗生素耐药性并调整其抗生素剂量方案。培养技术仍然不太可能显着缩短总检测时间(TAT),因此,该系统的重点是改进 TAT。通过使用分子技术直接从 BSI 患者的新鲜全血样本中鉴定和表征微生物敏感性特征,可以通过利用血液裂解离心来缩短获得结果的时间。获得临床分离株将导致最佳的周转时间 该应用的总体假设。
CentriFluidic 系统可用于直接从全血中执行快速 PID 和 AST,无需血液培养或 PCR 扩增,这是基于我们直接从原始尿液样本中进行的尿路感染 (UTI) 成功的临床可行性研究,并具有可重复的演示我们开发、演示并发表了一种创新的基于分子的基因型-表型-混合方法,用于多重细菌 PID 和耐药性分析。在我们最近对 73 个原始临床尿液样本进行的临床可行性研究中,AST 分析具有 100% 的临床敏感性、96% 的临床特异性、98% 的最低抑制浓度 (MIC) 和 97% 的绝对一致性。然而,当前 UTI 平台的关键局限性。存在的问题包括无法检测丰度低得多的血源性病原体、缺乏与超速离心模块的系统集成以及无法覆盖 BSI 的所有临床相关病原体。该 RO1 研究项目旨在结合实验室自动化、快速分子分析、熔解曲线特征分析、基因型病原体定量和表型抗生素条件的优势,显着提高直接从患者血液中快速、基于证据的 PID 和 AST 的灵敏度和特异性我们建议测试以下假设: 具体目标 1:将当前基于电化学的分子分析 PID/AST 平台技术从 UTI 过渡到 BSI - 假设:裂解离心可以解决这一问题。从原尿样品到全血样品的基质效应变化以及 BSI 病原体丰度低的问题 具体目标 2:开发基于双模式电化学的动态杂交分析算法以扩展 BSI PID/AST 组合 - 假设:动态杂交。分析可用于扩大 BSI 常见和新出现病原体的物种特异性识别。具体目标 3:原型设计、验证和制造 CentriFluidic 盒和系统 - 假设:超速离心(高达 50,000 g,重力)可集成到多重流体卡盒中,以实现完全自动化
3 小时内从全血样本中获得 BSI PID/AST 具体目标 4:根据 CLSI 指南对快速 BSI PID/AST CentriFluidic 系统进行临床验证 - 假设:分析验证研究中使用的添加了 ATCC 菌株的血液样本代表了关键的基质特征。来自患者的新鲜全血样本。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Vincent Jen-Jr Gau其他文献
Vincent Jen-Jr Gau的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Vincent Jen-Jr Gau', 18)}}的其他基金
Promote HPV screening rate with a non-invasive HPV POC cartridge
使用非侵入性 HPV POC 检测盒提高 HPV 筛查率
- 批准号:
8962209 - 财政年份:2015
- 资助金额:
$ 70.42万 - 项目类别:
An antibiogram-based CentriCapillary system for neonatal sepsis PID and AST
基于抗菌谱的 CentriCapillary 系统,用于治疗新生儿败血症 PID 和 AST
- 批准号:
8906593 - 财政年份:2015
- 资助金额:
$ 70.42万 - 项目类别:
A fully integrated CentriFluidic system for direct bloodstream infection PID/AST
用于直接血流感染 PID/AST 的完全集成 CentriFluidic 系统
- 批准号:
9015781 - 财政年份:2015
- 资助金额:
$ 70.42万 - 项目类别:
An antibiogram-based CentriCapillary system for neonatal sepsis PID and AST
基于抗菌谱的 CentriCapillary 系统,用于治疗新生儿败血症 PID 和 AST
- 批准号:
9170096 - 财政年份:2015
- 资助金额:
$ 70.42万 - 项目类别:
An Integrated Diagnostic System for Rapid Antimicrobial Susceptibility Testing
用于快速抗菌药物敏感性测试的集成诊断系统
- 批准号:
8655138 - 财政年份:2010
- 资助金额:
$ 70.42万 - 项目类别:
An Integrated Diagnostic System for Rapid Antimicrobial Susceptibility Testing
用于快速抗菌药物敏感性测试的集成诊断系统
- 批准号:
8477118 - 财政年份:2010
- 资助金额:
$ 70.42万 - 项目类别:
Near patient molecular diagnostics test for infections
患者附近感染分子诊断测试
- 批准号:
9202870 - 财政年份:2010
- 资助金额:
$ 70.42万 - 项目类别:
Rapid Prototyping Method and Design Library for Universal POC Application
通用POC应用的快速原型方法和设计库
- 批准号:
8001583 - 财政年份:2010
- 资助金额:
$ 70.42万 - 项目类别:
Near patient molecular diagnostics test for infections
患者附近感染分子诊断测试
- 批准号:
9540791 - 财政年份:2010
- 资助金额:
$ 70.42万 - 项目类别:
Rapid Antibiotic Susceptibility Testing for Neonatal Intensive Units
新生儿重症监护病房的快速抗生素敏感性测试
- 批准号:
7903816 - 财政年份:2010
- 资助金额:
$ 70.42万 - 项目类别:
相似国自然基金
SGO2/MAD2互作调控肝祖细胞的细胞周期再进入影响急性肝衰竭肝再生的机制研究
- 批准号:82300697
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
Tenascin-X对急性肾损伤血管内皮细胞的保护作用及机制研究
- 批准号:82300764
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
ACSS2介导的乙酰辅酶a合成在巨噬细胞组蛋白乙酰化及急性肺损伤发病中的作用机制研究
- 批准号:82370084
- 批准年份:2023
- 资助金额:48 万元
- 项目类别:面上项目
KIF5B调控隧道纳米管介导的线粒体转运对FLT3-ITD阳性急性髓系白血病的作用机制
- 批准号:82370175
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
PHF6突变通过相分离调控YTHDC2-m6A-SREBP2信号轴促进急性T淋巴细胞白血病发生发展的机制研究
- 批准号:82370165
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
相似海外基金
Developing a novel class of peptide antibiotics targeting carbapenem-resistant Gram-negative organisms
开发一类针对碳青霉烯类耐药革兰氏阴性生物的新型肽抗生素
- 批准号:
10674131 - 财政年份:2023
- 资助金额:
$ 70.42万 - 项目类别:
Development of a broad spectrum teixobactin-lipopeptide hybrid for the treatment of lung infections caused by pan-drug resistant ‘superbugs’
开发广谱替克菌素-脂肽杂合体,用于治疗泛耐药“超级细菌”引起的肺部感染
- 批准号:
10650420 - 财政年份:2022
- 资助金额:
$ 70.42万 - 项目类别:
Repurposing Gram-positive Antibiotics for Gram-Negative Bacteria using Antibiotic Adjuvants
使用抗生素佐剂重新利用革兰氏阳性抗生素治疗革兰氏阴性菌
- 批准号:
10708102 - 财政年份:2022
- 资助金额:
$ 70.42万 - 项目类别:
Development of a broad spectrum teixobactin-lipopeptide hybrid for the treatment of lung infections caused by pan-drug resistant ‘superbugs’
开发广谱替克菌素-脂肽杂合体,用于治疗泛耐药“超级细菌”引起的肺部感染
- 批准号:
10503471 - 财政年份:2022
- 资助金额:
$ 70.42万 - 项目类别:
Repurposing Gram-positive Antibiotics for Gram-Negative Bacteria using Antibiotic Adjuvants
使用抗生素佐剂重新利用革兰氏阳性抗生素治疗革兰氏阴性菌
- 批准号:
10587015 - 财政年份:2022
- 资助金额:
$ 70.42万 - 项目类别: