Abstract：
Pyrazinamide (PZA) is a key component of chemotherapy for the treatment of drug-susceptible tuberculosis (TB) and is likely to continue to be included in new drug combinations. Potentiation of PZA could be used to reduce the emergence of resistance, shorten treatment times, and lead to a reduction in the quantity of PZA consumed by patients, thereby reducing the toxic effects. Acidified medium is required for the activity of PZA against Mycobacterium tuberculosis. In vitro assessments of pyrazinamide activity are often avoided because of the lack of standardization, which has led to a lack of effective in vitro tools for assessing and/or enhancing PZA activity.We have developed and optimized a novel, robust, and reproducible, microtiter plate assay, that centers around acidity levels that are low enough for PZA activity. The assay can be applied to the evaluation of novel compounds for the identification of potentiators that enhance PZA activity. In this assay, potentiation of PZA is demonstrated to be statistically significant with the addition of rifampicin (RIF), which can, therefore, be used as a positive control. Conversely, norfloxacin demonstrates no potentiating activity with PZA and can be used as a negative control. The method, and the associated considerations, described here, can be adapted in the search for potentiators of other antimicrobials.
摘要：
吡嗪酰胺（PZA）是用于治疗药物敏感性结核病（TB）的化学疗法的关键成分，并且可能会继续被包括在新的药物组合中。PZA的增强可用于减少抗性的出现，缩短治疗时间，并导致患者消耗的PZA数量减少，从而减少毒性作用。PZA对结核分枝杆菌的活性需要酸化培养基。由于缺乏标准化，通常避免对吡嗪酰胺活性进行体外评估。这导致缺乏用于评估和/或增强PZA活性的有效体外工具。我们开发并优化了一部小说，健壮,和可重复的，微量滴定板测定，以酸度水平为中心，该酸度水平对于PZA活性而言足够低。该测定法可用于评价新化合物,以鉴定增强PZA活性的增效剂。在这个试验中,通过添加利福平（RIF），证明PZA的增强具有统计学意义。它可以，因此,用作阳性对照。相反，诺氟沙星与PZA没有增强活性，可用作阴性对照。方法,以及相关的考虑，在这里描述，可以在寻找其他抗菌剂的增效剂时进行调整。
