Novel clinical assay to rapidly monitor posaconazole levels in plasma

快速监测血浆中泊沙康唑水平的新型临床检测方法

• 批准号: 10246670
• 负责人: JONATHAN A HODGES
• 金额: $ 29.45万
• 依托单位: AFFINERGY, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-02 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10246670
• 关键词: Adoption; Affinity; Americas; Antifungal Agents; Aspergillus; Bacteriophages; Binding; Biological Assay; Buffers; Candida; Candida albicans; Cessation of life; Clinical; Clinical Chemistry; Communicable Diseases; Complex; Cryptococcus; Cytochrome P450; Detection; Dose; Drug Monitoring; Endogenous Factors; Ensure; Enzymes; Exposure to; FDA approved; Guidelines; HIV; Health; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; High Pressure Liquid Chromatography; Hospital Mortality; Immobilization; Immunocompromised Host; Individual; Infection; Institutes; Institution; Laboratories; Life; Mass Spectrum Analysis; Measurement; Measures; Monitor; Mycoses; Output; Pathway interactions; Patients; Peptides; Performance; Phage Display; Pharmaceutical Preparations; Phase; Plasma; Production; Prophylactic treatment; Reagent; Resistance development; Risk; Sampling; Signal Transduction; Sirolimus; Societies; Sterols; Technology; Tenofovir; Testing; Therapeutic; Time; Toxic effect; Transplant Recipients; Triazoles; base; commercialization; cost; detection limit; effective therapy; high risk; individual variation; infection risk; magnetic beads; mortality; novel; oropharyngeal thrush; posaconazole; pressure; prevent; protein aminoacid sequence; rapid test; reagent testing; resistant strain; routine care; scale up; validation studies; verification and validation

SUMMARY/ABSTRACT Invasive fungal infections (IFIs) contribute to more than 1.5 million deaths worldwide each year and pose a serious and continuous health risk to immunocompromised individuals. The rate of mortality associated with IFI is high, and there are only four major classes of antifungal drugs available to treat IFI, of which the triazoles find greatest use. Posaconazole (PCZ; Noxafil®) is the newest triazole and is the broadest spectrum, demonstrating activity against Aspergillus, Candida and Cryptococcus species. PCZ is indicated in the U.S. for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk for these infections, including hematopoietic stem cell transplant recipients, those with hematologic malignancies, and other immunocompromised patients. It is also indicated for treatment of oropharyngeal candidiasis (OTC), a condition common among HIV patients. While PCZ is not associated with significant toxicities, it displays high inter- and intra-individual variation in plasma drug concentrations, with subtherapeutic levels associated with poor efficacy. There is significant evidence to demonstrate that inadequate exposure to antifungals is independently associated with increased hospital mortality, and the Infectious Diseases Society of America recommends therapeutic drug monitoring (TDM) of PCZ to ensure adequate treatment. Unfortunately, there are currently no FDA approved assays available for performing PCZ TDM. Available assays remain limited to institutions or laboratories that have developed in-house laboratory-developed tests that rely on high- performance liquid chromatography (HPLC) or HPLC with mass spectrometry. These complex assays are expensive and lack harmonization, making it impossible to compare results from one test to the next. Most importantly, the turnaround time can range from several days to a week, making routine dose adjustments based on timely results impossible. Affinergy plans to develop a novel locking assay for the direct measurement of PCZ levels in plasma that is compatible with common clinical chemistry analyzers to facilitate routine TDM. Our assay with its lower cost and rapid turnaround will open access to a majority of patients to ensure that therapeutic levels are achieved to prevent life-threatening breakthrough infections and help control the rise of resistant strains.

摘要/文摘