Surveillance of pyrazinamide susceptibility among multidrug-resistant Mycobacterium tuberculosis isolates from Siriraj Hospital, Thailand.
Surveillance of pyrazinamide susceptibility among multidrug-resistant Mycobacterium tuberculosis isolates from Siriraj Hospital, Thailand.
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DOI：
10.1186/1471-2180-10-223
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发表时间：
2010-08-20
期刊：
影响因子：
4.2
通讯作者：
Chaiprasert A
中科院分区：
文献类型：
--
作者：
Jonmalung J;Prammananan T;Leechawengwongs M;Chaiprasert A
吡嗪酰胺（PZA）对结核分枝杆菌的药敏试验很难进行，因为药物活性所需的培养基酸度也会抑制细菌的生长。在泰国，关于PZA耐药性的信息非常有限，特别是从泰国分离出的耐多药结核病（MDR-TB）。泰国结核分枝杆菌菌株对PZA的敏感性仅报道了两项研究；一组使用吡嗪酰胺酶测定，另一组使用BACTEC 460 TB进行PZA药敏试验。本研究通过pyrazinamidase assay、BACTEC MGIT 960 PZA法和pncA测序，测定了泛敏感结核分枝杆菌和耐多药结核分枝杆菌中吡嗪酰胺耐药菌株的百分比，并评估了这些方法产生的数据之间的相关性。pncA的突变类型和频率也被确定。总体而言，通过BACTEC MGIT 960 PZA、吡嗪酰胺酶测定和pncA测序，对150株结核分枝杆菌（包括50株易感和100株耐多药结核分枝杆菌）进行了PZA敏感性检测。该研究表明，易感结核和耐多药结核分离株分别有6%和49%的PZA耐药。与BACTEC MGIT 960 PZA相比，PZase检测的灵敏度为65.4%，特异性为100%，而pncA测序的灵敏度为75%，特异性为89.8%。本研究共发现24种突变类型，其中最常见的突变为His71Asp（16%）。在这些突变中，有8个以前没有被描述过。在PZA易感株和耐药株中均发现Ile31Ser和Ile31Thr突变，提示该密码子突变可能与PZA耐药无关。我们的研究结果表明，表型敏感性检测仍然是检测PZA耐药性的必要条件，特别是对于耐多药结核分离株。一些突变与耐药性无关，可能导致对基因型方法的误解。这些信息可能有助于临床医生管理结核病患者和频率，pncA突变的类型应提供PZA耐药的基线信息。
Susceptibility testing of pyrazinamide (PZA) against Mycobacterium tuberculosis is difficult to perform because the acidity of culture medium that is required for drug activity also inhibits the growth of bacteria. In Thailand, very limited information has been generated on PZA resistance, particularly among multidrug-resistant tuberculosis (MDR-TB) isolated from Thailand. Only two studies on PZA susceptibility among Thai M. tuberculosis strains have been reported; one used a pyrazinamidase assay, and the other used the BACTEC 460 TB for PZA susceptibility testing. In this study, we determined the percentage of strains possessing pyrazinamide resistance among pan-susceptible M. tuberculosis and MDR-TB isolates by using the pyrazinamidase assay, BACTEC MGIT 960 PZA method and pncA sequencing, and assessed the correlation in the data generated using these methods. The type and frequency of mutations in pncA were also determined. Overall, 150 M. tuberculosis isolates, consisting of 50 susceptible and 100 MDR-TB isolates, were tested for PZA susceptibility by BACTEC MGIT 960 PZA, the pyrazinamidase assay and pncA sequencing. The study indicated PZA resistance in 6% and 49% of susceptible and MDR-TB isolates, respectively. In comparison to the BACTEC MGIT 960 PZA, the PZase assay showed 65.4% sensitivity and 100% specificity, whereas pncA sequencing showed 75% sensitivity and 89.8% specificity. Twenty-four mutation types were found in this study, with the most frequent mutation (16%) being His71Asp. Of these mutations, eight have not been previously described. The Ile31Ser and Ile31Thr mutations were found both in PZA susceptible and resistant isolates, suggesting that mutation of this codon might not play a role on PZA resistance. Our findings suggest that phenotypic susceptibility testing is still essential for the detection of PZA resistance, especially for MDR-TB isolates. Some mutations were not associated with resistance and could lead to misinterpretation of the genotypic methods. This information could be helpful for clinicians in managing tuberculosis patients and frequencies, and the types of pncA mutations should offer baseline information on PZA resistance.
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影响因子：
9.4
作者：
Scarparo, C;Ricordi, P;Piccoli, P
通讯作者：
Piccoli, P
影响因子：
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作者：
Singh, Pushpendra;Wesley, Clement;Katoch, V. A.
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