Pyrazinamide resistance among South African multidrug-resistant Mycobacterium tuberculosis isolates
Pyrazinamide resistance among South African multidrug-resistant Mycobacterium tuberculosis isolates
复制标题
DOI：
10.1128/jcm.00973-08
复制
发表时间：
2008-10-01
影响因子：
9.4
通讯作者：
Grewal, Harleen M. S.
中科院分区：
文献类型：
--
作者：
Mphahlele, Matsie;Syre, Heidi;Grewal, Harleen M. S.
吡嗪酰胺在结核病治疗中很重要，因为它对半分枝杆菌具有杀菌作用，而其他抗结核药物不能杀死它。吡嗪酰胺也是治疗耐多药结核病（MDR-TB）的基础药物之一。然而，由于技术上的困难，在许多实验室中没有进行结核分枝杆菌对吡嗪酰胺的常规药物敏感性测试。本研究的目的是在南非MDR和敏感M.肺结核病人的肺结核分离物。71例MDR和59例完全敏感M。通过放射性Bactec 460 TB系统、吡嗪酰胺酶活性（通过韦恩氏测定法）和pncA基因测序，检测在国家监测研究（2001 - 2002年，由南非医学研究理事会进行）期间收集的结核病分离株的吡嗪酰胺敏感性。MDR M中吡嗪酰胺耐药（Bactec系统）的频率。在完全敏感菌株中，结核菌株37/71（52.1%）和6/59（10.2%）。在pncA基因中总共检测到25个独特的突变。其中大多数是导致氨基酸取代的点突变。28个分离株在pncA基因中具有相同的突变，但可以通过spoligotype模式和12个分枝杆菌散布的重复单位位点的组合来彼此区分。南非MDR M.结核病分离株对吡嗪酰胺耐药，这表明对吡嗪酰胺在既往接受过结核病治疗的患者中的作用以及其在MDR-TB治疗中的作用进行了评价。
Pyrazinamide is important in tuberculosis treatment, as it is bactericidal to semidormant mycobacteria not killed by other antituberculosis drugs. Pyrazinamide is also one of the cornerstone drugs retained in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, due to technical difficulties, routine drug susceptibility testing of Mycobacterium tuberculosis for pyrazinamide is, in many laboratories, not performed. The objective of our study was to generate information on pyrazinamide susceptibility among South African MDR and susceptible M. tuberculosis isolates from pulmonary tuberculosis patients. Seventy-one MDR and 59 fully susceptible M. tuberculosis isolates collected during the national surveillance study (2001 to 2002, by the Medical Research Council, South Africa) were examined for pyrazinamide susceptibility by the radiometric Bactec 460 TB system, pyrazinamidase activity (by Wayne's assay), and sequencing of the pncA gene. The frequency of pyrazinamide resistance (by the Bactec system) among the MDR M. tuberculosis isolates was 37 of 71 (52.1%) and 6 of 59 (10.2%) among fully sensitive isolates. A total of 25 unique mutations in the pncA gene were detected. The majority of these were point mutations that resulted in amino acid substitutions. Twenty-eight isolates had identical mutations in the pncA gene, but could be differentiated from each other by a combination of the spoligotype patterns and 12 mycobacterial interspersed repetitive-unit loci. A high proportion of South African MDR M. tuberculosis isolates were resistant to pyrazinamide, suggesting an evaluation of its role in patients treated previously for tuberculosis as well as its role in the treatment of MDR-TB.