Khan Muhammad Tahir, Malik Shaukat Iqbal, Ali Sajid, Sheed Khan Anwar, Nadeem Tariq, Zeb Muhammad Tariq, Masood Nayyer, Afzal Muhammad Tanvir
1 Department of Bioinformatics and Biosciences, Capital University of Science and Technology , Islamabad, Pakistan .
2 Provincial Tuberculosis Reference Lab, Hayatabad Medical Complex , Peshawar, Pakistan .
Microb Drug Resist. 2018 Nov;24(9):1417-1421. doi: 10.1089/mdr.2017.0234. Epub 2018 Mar 27.
Pyrazinamide (PZA) is an important component of first-line tuberculosis (TB) treatment because of its distinctive capability to kill subpopulations of persister Mycobacterium tuberculosis (MTB). The significance of PZA can be understood by its inclusion in the most recent World Health Organization-recommended multidrug-resistant (MDR) TB regimen. Very little information is available about the prevalence of PZA-resistant TB from geographically distinct regions of high burden countries, including Khyber Pakhtunkhwa (KPK), Pakistan, because drug susceptibility testing (DST) of PZA is not regularly performed due to the complexity. In this study, we aimed to find the prevalence of PZA resistance in geographically distinct, Pashtun-dominant KPK Province of Pakistan and its correlation with other first- and second-line drug resistance.
In this study, DST of PZA was performed through an automated BACTEC MGIT 960 system (BD Diagnostic Systems). The resistant samples were further subjected to DST of isoniazid (INH), rifampicin (RIF), ethambutol (EMB), streptomycin (SM), moxicillin (MOX), amikacin (AMK), ofloxacin (OFX), kanamycin (KM), and capreomycin (CAP).
Out of 1,075 MTB-positive isolates, 83 (7.7%) were found to be resistant to PZA. Among the PZA-resistant isolates, 76 (90-91.6%) and 67 (80-80.7%) were found to be resistant to INH and RIF, respectively, whereas 63 (76%) were resistant to both first-line drugs, INH and RIF (MDR-TB). The resistance level of EMB, OFX, and SM was also significantly high in PZA resistance, 35 (42%), 40 (48%), and 41 (49-50%) respectively.
PZA resistance is significantly associated with other first- and second-line drug resistance. A significant number of PZA-resistant isolates are MDR cases. Therefore, DST of PZA should regularly be performed along with other drugs for better management of treatment of MDR and extensively drug resistant (XDR), to avoid side effects in patients.
吡嗪酰胺（PZA）是一线结核病（TB）治疗的重要组成部分，因为它具有独特的能力来杀死持留结核分枝杆菌（MTB）亚群。PZA的重要性可以通过其被纳入世界卫生组织最新推荐的耐多药（MDR）结核病治疗方案来理解。关于包括巴基斯坦开伯尔-普赫图赫瓦省（KPK）在内的高负担国家不同地理区域耐PZA结核病的流行情况，目前所知甚少，因为由于操作复杂，PZA的药物敏感性试验（DST）并未定期开展。在本研究中，我们旨在查明巴基斯坦以普什图族为主的不同地理区域的KPK省耐PZA情况及其与其他一线和二线药物耐药性的相关性。
在本研究中，通过自动化的BACTEC MGIT 960系统（BD诊断系统）进行PZA的DST。对耐药样本进一步进行异烟肼（INH）、利福平（RIF）、乙胺丁醇（EMB）、链霉素（SM）、莫西沙星（MOX）、阿米卡星（AMK）、氧氟沙星（OFX）、卡那霉素（KM）和卷曲霉素（CAP）的DST。
在1075株MTB阳性分离株中，发现83株（7.7%）对PZA耐药。在耐PZA的分离株中，分别有76株（90 - 91.6%）和67株（80 - 80.7%）对INH和RIF耐药，而63株（76%）对一线药物INH和RIF均耐药（MDR-TB）。在耐PZA情况中，EMB、OFX和SM的耐药水平也显著较高，分别为35株（42%）、40株（48%）和41株（49 - 50%）。
耐PZA与其他一线和二线药物耐药性显著相关。大量耐PZA的分离株为MDR病例。因此，为了更好地管理MDR和广泛耐药（XDR）结核病的治疗，避免患者出现副作用，应定期对PZA与其他药物一起进行DST。
