标准耐多药结核病化疗方案中是否对吡嗪酰胺耐药的疗效对比研究

A comparative study of the efficacy of standard multidrug-resistant tuberculosis chemotherapy regimen for MDR-TB patients with pyrazinamide resistance or not

目的探讨吡嗪酰胺(PZA)耐药与否对耐多药结核病(MDR-TB)患者采用含PZA的标准MDR-TB方案近远期临床疗效的影响关系。方法采用回顾性队列研究方法,选取2015年1—12月在广州市胸科医院就诊并顺利完成疗程,且采用BACTEC MGIT 960法检测有结核分枝杆菌生长,并同时采用比例法进行药物敏感性试验(简称“药敏试验”)证实对异烟肼、利福平和PZA耐药的MDR-TB患者(Z^R-MDR组)60例;采用1:1配对原则,选择同期治疗药敏试验结果显示对PZA敏感、年龄相差5岁以内的MDR-TB患者(Z^S-MDR组)60例。所有患者均给予化疗方案6Am-Lfx(Mfx)-PZA-Pto-Cs(PAS)/18Lfx(Mfx)-PZA-Pto-Cs(PAS)进行治疗。记录两组患者痰菌阴转率、病灶吸收率、空洞缩小率、治愈率及失败率等,并进行统计学分析。结果 Z^S-MDR组患者在2、6、12、24个月末时痰菌阴转率分别为70.00%(42/60)、90.00%(54/60)、86.67%(52/60)、86.67%(52/60),高于Z R-MDR组的46.67%(28/60)、66.67%(40/60)、70.00%(42/60)、70.00%(42/60),差异均有统计学意义(χ^2 值分别为6.720、9.624、4.910、4.910,P值均<0.05);疗程结束时Z^S-MDR组患者病灶吸收率为81.67%(49/60),高于Z R-MDR组的65.00%(39/60),差异有统计学意义(χ^2=4.264,P=0.019);Z^S-MDR组患者空洞缩小率为76.92%(40/52),与Z^R-MDR组的62.00%(31/50)间比较,差异无统计学意义(χ^2=2.681,P=0.098);Z^S-MDR组的治愈率为86.67%(52/60),高于Z^R-MDR组的70.00%(42/60),差异有统计学意义(χ^2=4.910,P=0.016)。Z^S-MDR组的失败率为13.33%(8/60),低于Z^R-MDR组的30.00%(18/60),差异有统计学意义(χ^2=4.910,P=0.016)。结论 PZA表型耐药的MDR-TB患者使用全程含PZA的标准耐多药方案治疗,其疗效较PZA敏感者差,建议对耐PZA的MDR-TB患者尽量选择不含PZA的耐多药化疗方案治疗。

Objective To explore the the short-term and long-term efficacy of standard multidrug-resistant tuberculosis (MDR-TB) chemotherapy regimen including PZA for MDR-TB patients with or without pyrazinamide resistance. Methods A retrospective cohort study was conducted to select 60 MDR-TB patients treated in Guangzhou Chest Hospital from January 1, 2015 to December 31, 2015;sputum culture showed the growth of Mycobacterium tuberculosis using BACTEC MGIT 960, and resistance to Isoniazid, Rifampicin and PZA (Z^R-MDR group) were found by drug sensitive test. According to the 1∶1 principle, 60 multidrug resistant-tuberculosis patients were selected as control group (Z^S-MDR group), the age difference was less than 5 years and the concurrent drug sensitivity test showed that they are sensitive to PZA. All patients were treated with chemotherapy regimen with 6Am-Lfx(Mfx)-PZA-Pto-Cs(PAS)/18Lfx(Mfx)-PZA-Pto-Cs(PAS). The sputum negative conversion rate, the absorption rate of lesions, the rate of cavity reduction, the cure rate and failure rate were conducted and analysed statistically. Results At the end of the 2,6,12, and 24 months after undergoing the treatment, sputum negative conversion rates of Z^S-MDR patients were 70.00%(42/60), 90.00%(54/60), 86.67%(52/60) and 86.67%(52/60), respectively, which were statistically higher than those of Z^R-MDR group (46.67%(28/60), 66.67%(40/60), 70.00%(42/60) and 70.00%(42/60), respectively;χ^2=6.720, 9.624, 4.910 and 4.910, respectively;and all P<0.05).At the end of the treatment, the absorption rate of lesions (81.67%(49/60) vs. 65.00%(39/60),χ^2=4.264,P=0.019), cure rate (86.67%(52/60) vs. 70.00%(42/60),χ^2=4.910, P=0.016) and failure rate (13.33%(8/60) vs. 30.00%(18/60),χ^2=4.910, P=0.016) in Z S-MDR group were statistically different from those in Z^R-MDR group. However, as to the rate of cavity reduction, there was no statistically significant difference between the two groups (76.92%(40/52)vs. 62.00%(31/50,χ^2=2.681, P=0.098). Conclusion The efficacy of standard MDR-TB chemotherapy regimen in MDR-TB patients with PZA resistance for the whole course, was worse than in MDR-TB patients without PZA. Therefore, MDR-TB patients with PZA resistance were recommended tobe treated with the multi-drug regimen without PZA.