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)是一种普遍的疾病，对儿童的影响不成比例， 这可能会导致严重的并发症，包括运动功能丧失和骨骼畸形。快速准确的诊断 OAI病因的选择对于选择特定和有针对性的治疗方案并改善预后至关重要 儿科病人。然而，在临床实践中，患者往往是从等待病原体的广谱抗生素开始的。 通过培养或聚合酶链式反应进行鉴定，这可能需要几天时间才能完成。此外，高 培养阴性的OAI比率和抗生素耐药菌株的增加使治疗决策独一无二 对OAI来说是一个挑战。同时，使用多种抗生素的非特异性治疗方案可能导致多个短期和长期- 长期不良影响。在这里，我们建议开发和测试MasSpec Pen(MSPen)技术作为一种创新方法 用于直接从临床标本中快速准确地鉴定OAI。我们开发的MSPen是一款易于使用的 集成到高性能质谱仪的手持设备，用于快速(&lt；20秒)检测丰富的新陈代谢 直接从生物样本中提取样本。现在，我们假设MSPen可以被开发成一种强大的技术 用于快速、直接和准确地从OAI临床样本中识别病原体，从而促进对 通过允许选择特定的和有针对性的治疗方法来治疗儿科患者。通过Livia S. Eberlin(德克萨斯大学奥斯汀分校化学系)，质谱学专家和 MSPen技术、Sarmistha B.Hauger博士(戴尔医学院儿科传染病科主任)和Lindsey博士 Kirkpatrick(印第安纳大学医学院传染病学院)，他的医疗实践致力于 对于儿科感染的治疗，我们建议通过实现以下具体目标来验证我们的假设： 目的1.优化MSPen方法用于儿科OAI临床标本及相关培养的分子分析 分离株。MSPen在复杂生物的直接分析中提供了变革性的分子检测能力 样品以及对常规临床使用有吸引力的操作特征。我们将改进设备和方法，以 优化其分析性能，用于OAI临床标本和相应培养的直接分子分析 分离株。目的2.确定MSPEN在儿童OAI病原体鉴定中的诊断性能 样本。MSPen具有提供分子信息的潜力，以推动快速准确的治疗决策- 制作。我们将分析为我们的研究收集的儿科OAI样本，包括与临床相关的样本 细菌菌株。将开发统计分类器，以使用临床将细菌病原体分类到分类水平 微生物学结果是金标准。目的3.评价MSPen用于抗生素鉴定的能力 耐药细菌菌株。表现为OAI的儿科患者中耐药菌的增加 揭示了准确识别抗生素敏感性的迫切需要。我们将调查MSPen的能力 用于鉴定临床样本中的抗生素耐药和敏感细菌。统计分类器将发展为 以临床微生物学结果为金标准，确定耐药或敏感的金黄色葡萄球菌。