Diagnosis and Tracking of Spinal Staphylococcus aureus Orthopaedic Implant Infections
脊柱金黄色葡萄球菌骨科植入物感染的诊断和追踪
基本信息
- 批准号:10554426
- 负责人:
- 金额:$ 23.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-01-24 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AnatomyAntibiotic TherapyAntibodiesAntibody titer measurementAntibody-Producing CellsAntigensB-Cell ActivationBenchmarkingBiologicalBiological AssayBloodBlood TestsBlood specimenBody TemperatureC-reactive proteinCell Culture TechniquesCell secretionCirculationClinicalCollecting CellComplexComplicationCultured CellsDataDeath RateDevicesDiagnosisDiagnosticDiagnostic ProcedureDiagnostic testsDisadvantagedEarly InterventionEnvironmentErythrocyte Sedimentation RateFeverGoalsHarvestImmune responseImmunoassayImmunoglobulin GImmunoglobulin-Secreting CellsImplantIn VitroInfectionInfectious AgentInfectious Skin DiseasesJoint ProsthesisKneeLearningLiquid substanceMasksMeasurementMeasuresMethodsMicrobial BiofilmsMonitorMorbidity - disease rateMusculoskeletalNeurologic SymptomsNomogramsOperative Surgical ProceduresOrganismOrthopedicsOutcomePainPatientsPeripheral Blood Mononuclear CellPolymersPostoperative PeriodPractice GuidelinesPropertyRapid diagnosticsReactionSamplingSecond Look SurgerySerumSerum MarkersSiteSpinalStaphylococcus aureusStaphylococcus aureus infectionSurfaceSurgical Wound InfectionTemperatureTestingTherapeuticTherapeutic InterventionTimeVertebral columnWhite Blood Cell Count procedureWhole BloodWorkantimicrobialcostcytokinediagnostic accuracydiagnostic tooldiagnostic valueexperienceextracellularfootimplant associated infectionimplantationin vivojoint infectionnovelpathogenprognosticresponsespine bone structurestandard of caresuccesstreatment guidelinestreatment responseusability
项目摘要
Spinal infections are a serious complication of vertebral implantation surgery with a death rate as high as 20%
in the first year. Challenging to identify, especially in the early stages, they are typically diagnosed after
becoming well established when the patient is experiencing significant pain and permanent vertebral damage.
Here, we propose to explore the early immune response to these infections, focusing on Staphylococcus
aureus, (S. aureus), the most frequent and serious among the multiple pathogens that cause spinal implant
infections. Our goal is to develop a new way to diagnose spinal implant infections that will: 1) be usable early in
the infection's course, 2) cost less than current approaches, 3) require only a routine blood sample, and 4) be
capable of monitoring therapeutic success. Most patients have high circulating levels of S. aureus-specific
antibodies, and these levels increase with infection, but remain elevated long after the infection has been
resolved. To provide a more sensitive diagnostic tool and at the same time create a simple measure for
monitoring therapeutic success, we propose to measure the antibodies produced by circulating Antibody-
Secreting Cells (ASC) that are present in the blood while the infection is ongoing and rapidly decline thereafter.
ASC can be harvested from whole blood, washed free of serum antibodies, and cultured in vitro for a short
time. These cultured cells will secrete newly synthesized antibodies, as well as the cytokines, yielding “medium
enriched for newly synthesized antibodies” or MENSA, for short. Antibody titers of MENSA fluid against
antigens for specific pathogens and the cytokines being secreted can be measured using a multiplex
immunoassay. In this proposal, we hypothesize that the diagnosis and monitoring of treatment response due to
spine related S. aureus infection is feasible utilizing pathogen-specific antibodies secreted by ASC, and that
the antigenic signatures will be distinct compared to other musculoskeletal infections. To test this hypothesis,
we will examine MENSA antibody and cytokine levels in patients with a known or suspected infection
associated with previously placed spinal orthopedic implants. We will determine if MENSA antibodies alone or
in combination with cytokines can discriminate between patients with S. aureus infections or infections due to
other pathogens. Accuracy will be determined by comparing to the clinical gold standard of bacterial culture.
We will also determine if we can use MENSA to track the response to treatment for S. aureus infection. This
study is focused on S. aureus as we can diagnosis this pathogen via culture, giving us a benchmark for
accuracy, even though 48% of the time, the infectious agent in spine infections cannot be determined by
culture. This study is a proof-of-concept study that can be expanded to other pathogens that are complex to
diagnose while also monitoring treatment when direct culture methods become impractical. The goal of this
work is the creation of simple, inexpensive, rapid diagnostic method that can lead to earlier interventions and
better outcomes for spinal infections patients.
脊柱感染是椎体植入手术的严重并发症,死亡率高达20%
项目成果
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Cheryl Lynne Ackert-Bicknell其他文献
Cheryl Lynne Ackert-Bicknell的其他文献
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{{ truncateString('Cheryl Lynne Ackert-Bicknell', 18)}}的其他基金
Diagnosis and Tracking of Spinal Staphylococcus aureus Orthopaedic Implant Infections
脊柱金黄色葡萄球菌骨科植入物感染的诊断和追踪
- 批准号:
10464246 - 财政年份:2022
- 资助金额:
$ 23.18万 - 项目类别:
Identification of Novel Genes Impacting Osteoblast Activity
影响成骨细胞活性的新基因的鉴定
- 批准号:
10649471 - 财政年份:2021
- 资助金额:
$ 23.18万 - 项目类别:
Identification of Novel Genes Impacting Osteoblast Activity
影响成骨细胞活性的新基因的鉴定
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10312427 - 财政年份:2021
- 资助金额:
$ 23.18万 - 项目类别:
Identification of Novel Genes Impacting Osteoblast Activity
影响成骨细胞活性的新基因的鉴定
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Co-localizing Quantitative Trait Loci for Bone Mineral Density and HDL in Mice
小鼠骨矿物质密度和 HDL 的定量性状基因座的共定位
- 批准号:
8894967 - 财政年份:2014
- 资助金额:
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