Development and Evaluation of Novel Applied Diagnostic Platforms for Clinical Microbiology

临床微生物学新型应用诊断平台的开发和评估

• 批准号: 9552569
• 负责人: Anna Lau
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9552569
• 关键词: Antimicrobial Resistance; Antimicrobial susceptibility; Area; Biological Assay; Blood; Clinical; Clinical Microbiology; Complex; Data; Detection; Development; Diagnosis; Diagnostic; Evaluation; Goals; Guidelines; Infection; Infection Control; Laboratories; MALDI-TOF Mass Spectrometry; Mainstreaming; Manuals; Measures; Methods; Microbiology; Molecular; Monitor; Organism; Patient Care; Performance; Phenotype; Predictive Value; Predisposition; Proteomics; Reporting; Specimen; Standardization; System; Test Result; Testing; Time; Virtual System; Weight; antimicrobial; carbapenem resistance; carbapenemase; clinically significant; comparative; gastrointestinal; improved; microorganism; molecular phenotype; new technology; novel; novel diagnostics; novel therapeutics; pathogen; prospective; research and development; resistance gene; resistance mechanism; response; sterility testing; targeted treatment

Traditional microbiological work up is slow and sometimes inaccurate, relying on phenotypic culture identification followed by antimicrobial susceptibility testing. Newer technologies, such as matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and real-time molecular detection (antimicrobial resistance genes microarrays) have advanced the diagnostic capabilities of clinical microbiology laboratories and have created an exciting field for research and development. Given the in-depth and highly accurate (sometimes complex) results that are produced by such platforms, careful detailed analyses are required to better understand the clinical significance of the organisms identified and the resistance mechanisms detected. During this fiscal year, we performed a large retrospective analysis on the clinical performance of HardyCHROM CRE media for the detection of carbapenemase-producing organisms from surveillance cultures. Data showed a positive predictive value ranging 8-56% depending on the definition carbapenem resistant organisms applied which varies between states and national guidelines. This has a tremendous effect on applied infection control practices and antimicrobial choices in response to a potential clinical infection. We also performed a comparative evaluation of three phenotypic assays for the detection of carbapenemases, as well as a retrospective analysis on the performance and accuracy of MALDI-TOF MS and susceptibility testing directly from positive blood cultures. The latter has provided informative results for clinical microbiology reporting while awaiting standardized testing results. Quality improvement projects have included a prospective comparative evaluation of blood culture volume monitoring methods (weight vs virtual system), comparative analysis of a multiplex gastrointestinal pathogen panel with traditional methods, and a large comparative assessment of product sterility testing systems for novel therapies (traditional USP<71> manual method vs automated Bactec FX system and BacTAlert Dual-T system).

传统的微生物学检查依赖于表型培养物鉴定和随后的抗菌药物敏感性测试，速度缓慢且有时不准确。基质辅助激光解吸电离飞行时间质谱 (MALDI-TOF MS) 和实时分子检测（抗菌素耐药基因微阵列）等新技术提高了临床微生物实验室的诊断能力，并创造了一个令人兴奋的研究和开发领域。鉴于此类平台产生的深入且高度准确（有时复杂）的结果，需要进行仔细的详细分析，以更好地了解所识别的生物体和检测到的耐药机制的临床意义。 在本财年中，我们对 HardyCHROM CRE 培养基用于检测监测培养物中产生碳青霉烯酶的微生物的临床性能进行了大型回顾性分析。数据显示，阳性预测值范围为 8-56%，具体取决于所采用的碳青霉烯类耐药微生物的定义，而各州和国家指南之间的定义有所不同。这对针对潜在临床感染的感染控制实践和抗菌药物选择产生巨大影响。我们还对用于检测碳青霉烯酶的三种表型测定进行了比较评估，并对 MALDI-TOF MS 的性能和准确性进行了回顾性分析，并直接从阳性血培养物进行药敏试验。后者在等待标准化检测结果的同时为临床微生物学报告提供了信息丰富的结果。质量改进项目包括对血培养体积监测方法（重量与虚拟系统）的前瞻性比较评估、多重胃肠道病原体组与传统方法的比较分析，以及对新疗法的产品无菌测试系统的大型比较评估（传统 USP<71> 手动方法与自动化 Bactec FX 系统和 BacTAlert Dual-T 系统）。