Department of Chest Medicine, Taipei Veterans General Hospital, Shih-Pai Rd,, Taipei 112, Taiwan, ROC.
BMC Infect Dis. 2011 Sep 12;11:240. doi: 10.1186/1471-2334-11-240.
Pyrazinamide (PZA) is an important first-line drug in multidrug-resistant tuberculosis (MDRTB) treatment. However, the unreliable results obtained from traditional susceptibility testing limits its usefulness in clinical settings. The detection of pncA gene mutations is a potential surrogate of PZA susceptibility testing, especially in MDRTB isolates. The impact of genotypes of M. tuberculosis in pncA gene mutations also remains to be clarified.
MDRTB isolates were collected from six hospitals in Taiwan from January 2007 to December 2009. pncA gene sequencing, pyrazinamidase activity testing, and spoligotyping were performed on all of the isolates. PZA susceptibility was determined by the BACTEC MGIT 960 PZA method. The sensitivity and specificity of pncA gene analysis were estimated based on the results of PZA susceptibility testing.
A total of 66 MDRTB isolates, including 37 Beijing and 29 non-Beijing strains, were included for analysis. Among these isolates, 36 (54.5%) were PZA-resistant and 30 (45.5%) were PZA-susceptible. The PZA-resistant isolates were more likely to have concomitant resistance to ethambutol and streptomycin. Thirty-seven mutation types out of 30 isolates were identified in the pncA gene, and most of them were point mutations. The sensitivities of pncA gene sequencing for PZA susceptibility in overall isolates, Beijing and non-Beijing strains were 80.6%, 76.2%, and 86.7% respectively, and the specificities were 96.7%, 93.8%, and 100% respectively.
More than half of the MDRTB isolates in this study are PZA-resistant. Analysis of pncA gene mutations helped to identify PZA-susceptible MDRTB isolates, especially in non-Beijing strains.
吡嗪酰胺（PZA）是耐多药结核病（MDRTB）治疗中的重要一线药物。然而，传统药敏试验结果不可靠，限制了其在临床中的应用。pncA 基因突变的检测是吡嗪酰胺药敏试验的潜在替代方法，尤其是在 MDRTB 分离株中。结核分枝杆菌 pncA 基因突变的基因型对其的影响仍需阐明。
本研究收集了 2007 年 1 月至 2009 年 12 月期间台湾六家医院的 MDRTB 分离株。对所有分离株均进行 pncA 基因测序、吡嗪酰胺酶活性检测和 spoligotyping。采用 BACTEC MGIT 960 PZA 法测定 PZA 药敏性。根据 PZA 药敏试验结果，评估 pncA 基因分析的敏感性和特异性。
共纳入 66 株 MDRTB 分离株，其中包括 37 株北京株和 29 株非北京株。这些分离株中，36 株（54.5%）为 PZA 耐药，30 株（45.5%）为 PZA 敏感。PZA 耐药分离株更可能同时对乙胺丁醇和链霉素耐药。30 株 PZA 敏感分离株中有 37 种 pncA 基因突变类型，大多数为点突变。pncA 基因测序对总分离株、北京株和非北京株的 PZA 药敏性的敏感性分别为 80.6%、76.2%和 86.7%，特异性分别为 96.7%、93.8%和 100%。
本研究中超过一半的 MDRTB 分离株为 PZA 耐药。pncA 基因突变分析有助于鉴定 PZA 敏感的 MDRTB 分离株，尤其是非北京株。
