Pyrazinamide (PZA) is an important anti-tuberculosis drug, which is active against semi-dormant bacilli and used as a component of first-line drugs and drug-resistant tuberculosis regimens. Mutations in pncA and its promoter region are main cause of PZA resistance. There are limited PZA susceptibility data as there is no routine drug susceptibility testing (DST) for PZA. This study was aimed to determine the proportion of PZA resistance among rifampicin-resistant tuberculosis patients and to identify mutations which are responsible for PZA resistance in pncA and its promoter region. Liquid-based DST was performed to detect PZA susceptibility on 192 culture positive rifampicin-resistant isolates collected from National Tuberculosis Reference Laboratory. Sequencing on pncA including its promoter region was performed and analysis was done on 157 isolates. Phenotypic PZA resistance was detected in 58.9% of isolates. Sixty-five different mutations were distributed in pncA or promoter region of 82 isolates. Sensitivity and specificity of pncA sequencing in detection of PZA resistance showed 89.8% and 95.6% respectively. High proportion of PZA resistance among rifampicin-resistant cases highlighted the need for effective treatment regimen development for PZA-resistant MDR-TB. It is also suggested that routine PZA susceptibility test should be incorporated to treatment monitoring regimen and National Drug Resistance surveys.

中文翻译：

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来自缅甸的耐药结核分枝杆菌临床分离株的吡嗪酰胺耐药性和 pncA 突变

吡嗪酰胺（PZA）是一种重要的抗结核药物，对半休眠杆菌有活性，用作一线药物和耐药结核病方案的组成部分。pncA 及其启动子区域的突变是 PZA 抗性的主要原因。由于 PZA 没有常规药物敏感性测试 (DST)，因此 PZA 敏感性数据有限。本研究旨在确定利福平耐药结核病患者中 PZA 耐药的比例，并确定导致 pncA 及其启动子区域 PZA 耐药的突变。对从国家结核病参考实验室收集的 192 株培养阳性的利福平耐药菌株进行了基于液体的药敏试验，以检测 PZA 敏感性。对包括其启动子区域在内的 pncA 进行了测序，并对 157 个分离株进行了分析。在 58.9% 的分离株中检测到表型 PZA 抗性。65 个不同的突变分布在 82 个分离株的 pncA 或启动子区域。pncA 测序检测 PZA 耐药性的灵敏度和特异性分别为 89.8% 和 95.6%。利福平耐药病例中 PZA 耐药比例高突出表明需要为 PZA 耐药 MDR-TB 制定有效的治疗方案。还建议将常规 PZA 药敏试验纳入治疗监测方案和国家耐药性调查。pncA 测序检测 PZA 耐药性的灵敏度和特异性分别为 89.8% 和 95.6%。利福平耐药病例中 PZA 耐药比例高突出表明需要为 PZA 耐药 MDR-TB 制定有效的治疗方案。还建议将常规 PZA 药敏试验纳入治疗监测方案和国家耐药性调查。pncA 测序检测 PZA 耐药性的灵敏度和特异性分别为 89.8% 和 95.6%。利福平耐药病例中 PZA 耐药比例高突出表明需要为 PZA 耐药 MDR-TB 制定有效的治疗方案。还建议将常规 PZA 药敏试验纳入治疗监测方案和国家耐药性调查。