Development of the MasSpec Pen Technology for Rapid and Accurate Identification of Pediatric Infections

开发用于快速准确识别儿科感染的 MasSpec Pen 技术

• 批准号: 10317701
• 负责人: Livia Schiavinato Eberlin
• 金额: $ 25.88万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10317701
• 关键词: Adverse effects; Affect; Allergic Reaction; Antibiotic Resistance; Antibiotic Therapy; Antibiotic susceptibility; Antibiotics; Bacteria; Bacterial Antibiotic Resistance; Bacterial Infections; Biological; Biological Assay; Caliber; Cancer Diagnostics; Cartilage; Cells; Cessation of life; Chemistry; Child; Childhood; Clinical; Clinical Microbiology; Clostridium difficile; Colitis; Collaborations; Communicable Diseases; Complex; Decision Making; Deformity; Detection; Development; Devices; Diagnostic; Diarrhea; Drainage procedure; Epidemiology; Etiology; Excision; Faculty; Failure; Gold; Growth; Human; In Vitro; Incidence; Indiana; Infection; Joints; Kingella kingae; Laboratories; Lead; Lipids; Liquid substance; Mass Spectrum Analysis; Medical; Metabolic; Methods; Microbiology; Molecular; Molecular Analysis; Molecular Profiling; Motor; Operative Surgical Procedures; Osteomyelitis; Outcome; Patients; Performance; Polymerase Chain Reaction; Precision therapeutics; Prevalence; Regimen; Research; Resistance; Sampling; Sepsis; Solvents; Specimen; Staphylococcus aureus; Streptococcus; Surgical Oncology; Symptoms; System; Taxonomy; Technology; Testing; Texas; Therapeutic; Time; Tissues; Universities; accurate diagnosis; antimicrobial; austin; bacterial resistance; bone; chronic infection; clinical practice; clinically relevant; effective therapy; emerging pathogen; expectation; handheld equipment; improved; improved outcome; innovation; innovative technologies; joint destruction; mass spectrometer; medical schools; metabolic profile; methicillin resistant Staphylococcus aureus; new technology; pathogen; pathogenic bacteria; pediatric patients; prevent; prospective; rapid diagnosis; rapid technique; resistant strain; targeted treatment

ABSTRACT: Osteoarticular infections (OAI) are prevalent medical conditions that disproportionately affect children, which can lead to serious complications including loss of motor function and bone deformity. Rapid and accurate diagnosis of OAI etiologic agents are critical to allow selection of specific and targeted treatment options and improve outcomes for pediatric patients. Yet, in clinical practice, patients are often started on broad spectrum antibiotics pending pathogen identification by culture or polymerase chain reaction, which can take several days for completion. In addition, the high rates of culture-negative OAI and the increased prevalence of antibiotic resistant strains make therapeutic decisions uniquely challenging for OAI. Meanwhile, unspecific therapy regimens with multiple antibiotics can lead to multiple short- and long- term adverse effects. Here, we propose to develop and test the MasSpec Pen (MSPen) technology as an innovative method for rapid and accurate identification of OAI directly from clinical specimens. We developed the MSPen as an easy-to-use handheld device integrated to a high-performance mass spectrometer for rapid (<20 seconds) detection of rich metabolic profiles directly from biological samples. Now, we hypothesize that the MSPen can be developed as a powerful technology for rapid, direct, and accurate identification of etiologic agents from OAI clinical samples, thus advancing treatment for pediatric patients by allowing selection of specific and targeted therapy. Through a collaboration between Prof. Livia S. Eberlin (Department of Chemistry, The University of Texas at Austin), expert in mass spectrometry and developer of the MSPen technology, Dr. Sarmistha B. Hauger (Chief of Pediatric Infectious Disease, Dell Medical School) and Dr. Lindsey Kirkpatrick (Infectious Disease Faculty, Indiana University School of Medicine), whose medical practices are dedicated to the treatment of pediatric infections, we propose to test our hypothesis by carrying out the following specific aims: Aim 1. Optimize the MSPen assay for molecular analysis of pediatric OAI clinical specimens and associated culture isolates. The MSPen provides transformative molecular detection capabilities in the direct analysis of complex biological samples along with operational features that are attractive for routine clinical use. We will refine the device and method to optimize its analytical performance for direct molecular analysis of OAI clinical specimens and corresponding culture isolates. Aim 2. Determine the diagnostic performance of the MSPen for pathogen identification in pediatric OAI samples. The MSPen has the potential to provide molecular information to drive rapid and accurate therapeutic decision- making. We will analyze pediatric OAI samples prospectively collected for our study encompassing clinically-relevant bacteria strains. Statistical classifiers will be developed to classify bacterial pathogens into taxonomical levels using clinical microbiology results as gold-standard. Aim 3. Evaluate the capabilities of the MSPen for the identification of antibiotic resistant bacterial strains. The increasing occurrence of antibiotic resistant bacteria in pediatric patients presenting OAI reveals a critical need for accurate identification of antibiotic susceptibility. We will investigate the capability of the MSPen in identifying antibiotic resistant and susceptible bacteria in clinical samples. Statistical classifiers will be developed to identify resistant or susceptible S. aureus, using clinical microbiology results as gold-standard.

摘要：骨关节感染（OAI）是普遍的医疗状况，对儿童的影响不成比例， 这可能导致严重的并发症，包括运动功能的丧失和骨畸形。快速准确的诊断 OAI病因学剂对于允许选择特定和有针对性的治疗方案至关重要 小儿患者。然而，在临床实践中，患者经常以较广谱抗生素开始 通过培养或聚合酶链反应进行识别，这可能需要几天才能完成。此外，高 培养阴性OAI的速率和抗生素抗性菌株的患病率的增加使治疗决定独特 对OAI的挑战。同时，具有多种抗生素的非特异性治疗方案可导致多个短期和长期 术语不利影响。在这里，我们建议将MassPec Pen（MSPEN）技术作为创新方法开发和测试 直接从临床标本中直接鉴定OAI。我们开发了MSPEN作为易于使用的 集成到高性能质谱仪的手持设备，以快速（<20秒）检测丰富的代谢 直接来自生物样品。现在，我们假设MSPEN可以作为强大的技术开发 为了快速，直接和准确地鉴定OAI临床样本的病因学剂，从而推进治疗方法 小儿患者允许选择特定和靶向治疗。通过Livia S.教授之间的合作 埃伯林（德克萨斯大学奥斯汀分校化学系），质谱专家和开发商 Mspen Technology，Sarmistha B. Hauger博士（小儿传染病主任，戴尔医学院）和Lindsey博士 Kirkpatrick（印第安纳大学医学院传染病学院），其医学实践专门用于 小儿感染的治疗，我们建议通过执行以下特定目的来检验假设： 目标1。优化MSPEN测定法以分子分析小儿OAI临床标本和相关培养物 分离物。 MSPEN在复杂生物学的直接分析中提供了变换的分子检测能力 样品以及用于常规临床使用有吸引力的操作特征。我们将完善设备和方法 优化其分析性能，以直接对OAI临床标本和相应培养的分子分析 分离物。 AIM 2。确定MSPEN在小儿OAI中病原体鉴定的诊断性能 样品。 MSPEN有可能提供分子信息以推动快速，准确的治疗决策 - 制作。我们将分析针对我们的研究，包括临床上的研究 细菌菌株。将开发统计分类器将细菌病原体分类为分类学水平 微生物学结果是金标准。目标3。评估MSPEN鉴定抗生素的能力 抗性细菌菌株。出现OAI的儿科患者中抗生素耐药细菌的发生增加 揭示了准确鉴定抗生素易感性的迫切需要。我们将研究MSPEN的能力 在鉴定临床样品中的抗生素耐药性和易感细菌。统计分类器将被开发为 使用临床微生物学结果确定耐药或易感金黄色葡萄球菌。