Unidad de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Lima, Peru.
Microb Drug Resist. 2012 Aug;18(4):372-5. doi: 10.1089/mdr.2011.0207. Epub 2012 Feb 28.
Pyrazinamide (PZA) is an important drug in the treatment of tuberculosis. Microbiological methods of PZA susceptibility testing are controversial and have low reproducibility. After conversion of PZA into pyrazinoic acid (POA) by the bacterial pyrazinamidase enzyme, the drug is expelled from the bacteria by an efflux pump.
To evaluate the rate of POA extrusion from Mycobacterium tuberculosis as a parameter to detect PZA resistance.
The rate of POA extrusion and PZA susceptibility determined by BACTEC 460 were measured for 34 strains in a previous study. PZA resistance was modeled in a logistic regression with the pyrazinoic efflux rate.
POA efflux rate predicted PZA resistance with 70.83%-92.85% sensitivity and 100% specificity compared with BACTEC 460.
POA efflux rate could be a useful tool for predicting PZA resistance in M. tuberculosis. Further exploration of this approach may lead to the development of new tools for diagnosing PZA resistance, which may be of public health importance.
吡嗪酰胺(PZA)是治疗结核病的重要药物。PZA 药敏微生物学方法存在争议,重复性低。在细菌吡嗪酰胺酶的作用下,PZA 转化为吡嗪酸(POA)后,药物被外排泵排出细菌。
评估结核分枝杆菌中 POA 外排率作为检测 PZA 耐药性的参数。
我们之前的研究中测量了 34 株菌的 POA 外排率和 BACTEC 460 测定的 PZA 药敏性。用逻辑回归模型对吡嗪酸外排率进行 PZA 耐药性建模。
与 BACTEC 460 相比,POA 外排率对 PZA 耐药性的预测具有 70.83%-92.85%的敏感性和 100%的特异性。
POA 外排率可作为预测结核分枝杆菌中 PZA 耐药性的有用工具。进一步探索这种方法可能会开发出用于诊断 PZA 耐药性的新工具,这可能具有公共卫生意义。