SBIR Phase I: Development of reliable pyrazinamide susceptibility testing at neutral pH

这个小企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力旨在开发一种新的结核病检测方法。这项技术将比目前的护理标准产生更准确、更可靠的结果。该项目将改善结核病治疗结果。此外，它将通过提高治愈率和减少耐药性的传播来防治耐多药结核病日益增加的发病率。本小型企业创新研究（SBIR）一期项目拟采用TB药敏试验标准方案，在重组的中性pH条件下测定PZA在体内的药敏。目前的PZA药敏试验不可靠，因为它是在酸性pH条件下进行的。接种量不合适的结核分枝杆菌可能会中和培养基的pH值，或者在酸性条件下由于生长抑制而无法生长。这就导致经常出现错误的结果，导致治疗不当。拟议的研究将提出一种新的方法，在专有培养基中确定中性pH下PZA的表型敏感性。本项目将优化PZA药敏试验介质，采用TB药敏试验标准方案进行药敏试验，保证药敏试验的可靠性和准确性。总之，本研究不仅将建立可靠的PZA药敏检测方法，而且将所有结核药物的药敏结合在一个有效的系统中。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project aims to develop a new test for tuberculosis (TB). This technology will lead to more accurate and reliable results than the current standard of care. This project will improve TB treatment outcomes. Furthermore, it will combat the increasing incidence of multidrug-resistant TB by increasing the cure rate and reducing the spread of drug resistance. This Small Business Innovation Research (SBIR) Phase I project proposes to determine PZA susceptibility at neutral pH in reconstituted in vivo condition using the standard protocol of TB drug susceptibility testing. The current PZA susceptibility test is unreliable because it is performed in an acidic pH condition. An inappropriate inoculum size of M. tuberculosis may neutralize the pH of the medium or fail to grow due to growth inhibition at the acidic pH condition. This leads to frequent false results, leading to improper treatment. The proposed research will advance a novel approach, determining phenotypic PZA susceptibility at neutral pH in a proprietary culture media. This project will optimize the media for PZA susceptibility testing, and the susceptibility testing will be implemented using the standard protocol of TB drug susceptibility testing with reliability and accuracy. Together, this studies will not only establish a reliable PZA susceptibility testing, but also combine all TB drug susceptibilities in one effective system.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.