目的 分析中国南方地区一线抗结核药物耐药背景不同结核分枝杆菌吡嗪酰胺（PZA）耐药 率差异，探讨影响其 PZA 耐药的可能因素，为进一步揭示结核分枝杆菌 PZA 耐药机制提供研究基础。 方法 以 2012 年 11 月至 2018 年 12 月就诊于我院结核患者的结核分枝杆菌临床分离株为研究对象，依据 其对异烟肼、利福平、乙胺丁醇、链霉素（以下分别简称为 H、R、E、S）耐药性分组，分析此四种药物耐药组 合不同及利福平耐药特征不同结核分枝杆菌的 PZA 耐药率差异。结果 （1）耐 0、1、2、3、4 种上述抗结核 药物结核分枝杆菌的 PZA 耐药率分别为 3.75%、8.60%、28.21%、57.59%、75.74%，任意两组组间比较差异有 统计学意义（P < 0.005）；（2）利福平耐药和敏感的结核分枝杆菌 PZA 耐药率为分别为 56.03%和 12.51%，组 间比较差异有统计学意义（P < 0.05）；（3）四种药物全部敏感（Q），S、H、E、R、SE、RS、HS、RE、HR、HE、 HSE、RSE、HRS、HRE、HRSE 耐药结核分枝杆菌的 PZA 耐药率分别为 3.75%、4.92%、11.36%、12.12%、 17.78%、7.14%、18.00%、18.20%、37.50%、40.98%、48.57%、50.00%、50.00%、54.71%、70.18%、75.74%；15 组 耐药菌与全敏菌组间 PZA 耐药率比较差异显示：S、E、SE 耐药菌与全敏菌的 PZA 耐药率差异比较差异无 统计学意义（P > 0.003），余者组间比较差异有统计学意义（P < 0.003）。结论 利福平耐药与否、一线抗 结核药物耐药组合可能是影响结核分枝杆菌PZA 耐药的重要因素。

Objective To analyze the difference of pyrazinamide（PZA）resistance rates of Mycobacterium tuberculosis clinical isolates with different backgrounds of first ⁃line anti ⁃tuberculosis drug resistance in southern China，and explore the possible factors influencing PZA resistance in Mycobacterium tuberculosis，so as to provide a research basis for further revealing the PZA resistance mechanism of Mycobacterium tuberculosis. Methods The clinical isolates of Mycobacterium tuberculosis from tuberculosis patients in our hospital from november 2012 to december 2018 were taken as the research objects. According to their resistance groups to isoniazid，rifampicin， ethambutol and streptomycin（here in after referred to as H，R，E and S respectively），the differences of PZA resistance rates of Mycobacterium tuberculosis with different drug resistance combinations and rifampicin resistance characteristics were analyzed. Results （1）The PZA resistance rates of Mycobacterium tuberculosis resistant to 0， 1，2，3 and 4 kinds of anti⁃tuberculosis drugs mentioned above were 3.75%，8.60%，28.21%，57.59% and 75.74%， respectively. Chi ⁃ square test showed statistically significant differences between any two groups （P < 0.005）. （2）The resistance rates of rifampicin resistant and sensitive Mycobacterium tuberculosis to PZA were 56.03% and 12.51%，respectively，and the difference between the two groups was statistically significant（P < 0.05）（. 3）PZA resistance rates of drug sensitive（Q），and the S，H，E，R，SE，RS，HS，RE，HR，HE，HSE，RSE，HRS，HRE and HRSE resistant isolates are 3.75%，4.92%，11.36%，12.12%，17.78%，7.14%，18.00%，18.20%，37.50%， 40.98% ，48.57% ，50.00% ，50.00% ，54.71% ，70.18% and 75.74%respectively. Chi⁃square test showed that the differences of PZA resistance rates between 15 groups of drug⁃resistant bacteria and sensitive isolates group showed that the differences of PZA resistance rates between S，E，SE ⁃ resistant isolates and four drug sensitive isolates were 0.078，0.004 and 0.4160，respectively，with no statistical significance（P > 0.003），while differences in the other groups had statistical significance（P < 0.000）. Conclusions The resistance of rifampicin and the combina⁃ tion with other first ⁃line anti ⁃tuberculosis drugs resistance may be the important factors affecting the resistance of Mycobacterium tuberculosis to PZA.