UroLogic: Rapid, Near-to-Care Identification and Antimicrobial Susceptibility Testing of Microbes in Urine Specimens from Outpatients with Suspected Urinary Tract Infection

泌尿科：对疑似尿路感染的门诊患者尿液样本中的微生物进行快速、近乎护理的鉴定和抗菌药物敏感性测试

• 批准号: 9465905
• 负责人: BERNARD M CHURCHILL
• 金额: $ 30万
• 依托单位: MICROBEDX, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9465905
• 关键词: Address; Ampicillin; Antibiotic Resistance; Antibiotic Therapy; Antibiotic susceptibility; Antibiotics; Antimicrobial susceptibility; Bacteria; Biochemical; Biological; Biological Assay; Candida; Caring; Cefazolin; Ceftriaxone; Ciprofloxacin; Clavulanate; Clinic; Clinical; Communicable Diseases; Cytolysis; DNA; Detection; Devices; Diagnostic; Engineering; Enzyme-Linked Immunosorbent Assay; Evaluation; Feedback; Fosfomycin; Funding; Future; Gentamicins; Gram-Negative Bacteria; Health Personnel; Healthcare; Hour; Individual; Infection; Laboratories; Liquid substance; Manuals; Manufacturer Name; Methods; Microbe; Microbiology; Microfluidics; Modification; Nitrofurantoin; Optical Methods; Organism; Outcome; Outpatients; Patient Selection; Patients; Performance; Pharmaceutical Preparations; Phase; Phenotype; Physicians; Predisposition; Price; Primary Health Care; Randomized Controlled Trials; Reader; Reporting; Resistance; Ribosomal DNA; Ribosomal RNA; Sampling; Sensitivity and Specificity; Shipping; Ships; Signal Transduction; Small Business Innovation Research Grant; Specimen; Study Section; System; Systems Analysis; Testing; Time; Urinary tract infection; Urine; Uropathogen; Validation; Visit; Writing; antimicrobial; base; cost; design; detector; economic impact; experience; health care economics; instrument; novel diagnostics; pathogen; phase 1 testing; phase 2 study; prototype; response; urologic

Antibiotic resistance is a global healthcare crisis that is forcing physicians to treat common infectious diseases with ever more potent antibiotics. New diagnostic strategies are urgently needed for rapid pathogen identification/quantification (IDQ) and antimicrobial susceptibility testing (AST) to guide antibiotic selection for patients with urinary tract infection (UTI). MicrobeDx will design and test UroLogic, a highly automated, instrument and cartridge system that performs rapid, accurate pathogen IDQ and AST with turnaround times from sample to readout of 30 and 150 minutes, respectively. While validated, our current assays are manual and require a separate reader. The manual assays have delivered high sensitivity and specificity. We are developing a fully automated, near-to-care assay system that is affordable for clinics and conventional primary care offices. In Phase I, our Specific Aims are proof-of-concept validation that the IDQ and AST assays can be integrated into an alpha-prototype UroLogic system that meets the diagnostic milestones required for urine specimens to guide therapy for UTI. Aim 1: Evaluation of the Integrated IDQ Assay. We will evaluate the fluidic and analytic performance of the alpha-prototype UroLogic IDQ assay for identification and quantification of bacterial and fungal organisms as isolates and in urine specimens. Results will be compared with standard microbiological biochemical and plating methods. Aim 2: Evaluation of the Integrated AST Assay. We will evaluate the fluidic and analytic performance of the alpha-prototype UroLogic AST assay for antimicrobial susceptibility testing of Gram-negative bacteria as isolates and in urine specimens. Phenotypic methods such as ours are the best predictors of Gram-negative susceptibility. Tests of Feasibility: The alpha prototype system must demonstrate a clinically meaningful LOD (104 cfu/ml) and analytic IDQ and AST accuracy to FDA standards. In addition, the cost of goods device must achieve a price point ($4 IDQ cartridge, $5 AST cartridge, $10,000 instrument) low enough to allow broad dissemination. In future SBIR Phase II studies, additional engineering modifications will be to make this a clinically usable beta-prototype, as informed by feedback from Phase I, and test the entire system in clinical settings. Supported by later Phase IIb funds, we will then evaluate the use of the device in a randomized controlled trial (RCT) to determine analytic accuracy, clinical utility, and healthcare economic impacts.

抗生素耐药性是一场全球医疗危机，迫使医生治疗常见疾病