丙硫乙烟胺抗结核分枝杆菌临床耐药界限的研究

Study on clinical drug resistance breakpoints of prothionamide for Mycobacterium tuberculosis

目的通过测定丙硫乙烟胺(Th)对128株临床分离的结核分枝杆菌的最低抑菌浓度(MIC), 分析MIC与既往Th的用药史及经过含Th方案治疗的疗效相关性,以期确定Th的临床耐药界限。方 法住院的结核病患者128例,留取痰或体液进行结核分枝杆菌培养、药敏试验及MIC测定,并系统 观察47例肺结核患者接受Th治疗方案的痰菌阴转率,各组间率的比较用x2检验。结果(1)既往未接 受Th药物治疗的临床分离株中,MIC=2．5μg／mL者占72．5％,MIC≤5．0μg／mL者占77．5％;(2)既往曾 接受Th药物治疗的临床分离株中,MIC>5．0μg／mL者占96．4％;(3)如以MIC≥5．0 μg／mL,为临床耐药界 限,MIC<5．0μg／mL与MIC≥5．0μg／mL比较,3、6、12个月患者痰菌阴转率分别为53．6％、75．0％、82．1％及 15．8％,31．6％、42．1％,两组比较差异均有非常显著性(P<0．01)。结论(1)曾接受Th药物治疗的结核病 患者分离株MIC显著高于未接受Th治疗的患者,随着用药时间的延长,MIC随之升高;(2)根据MIC与 临床疗效分析结果,提示采用MIC≥5．0 μg／mL为临床耐药界限为宜;(3)既往曾接受Th药物治疗的结核 病患者,应进行Th的药敏试验,并坚持合理、联合用药的原则,防止耐药株的产生。

Objective To determine drug resistance breakpoints of Prothionamide by testing its MIC in 128 strains of Mycobacterium tuberculosis（M.TB） isolated from patients with active tuberculosis and analyzing the relationship between MIC and past history of prothionamide administration and therapeutic effects of regimen including prothionamide. Methods Isolated sputa or body fluids from 128 tuberculosis patients were cultured for M.TB, drug sensitive test and MIC determination. Sputum negative conversion rates of M.TB after prothionamide regimen treatment in 47 patients were observed consecutively. Chi-square test was employed for statistical analysis. Results （1） In patients without previous Prothionamide treatment, 72.5% with MIC=2.5μg/mL and 77.5% with MIC≤5.0μg/mL; （2） In patients with previous Prothionamide treatment, 96.4% with MIC〉5.0μg/mL; （3） If MIC≥5.0μg/mL was defined as clinical drug resistance breakpoints, in MIC〈5.0μg/mL group, sputum negative conversion rates were 53.6%, 75.0%, and 82.1% respectively after receiving Prothionamide regimen treatment for 3, 6, and 12 months. While inMIC≥5.0μg/mL group, they were 15.8%, 31.6%, and 42.1% respectively, and there was a significant difference between the two groups（P 〈0.01）. Conclusion （1） MIC in patients with previous Prothionamide treatment is much higher than it is in patients without previous Prothionamide treatment, and it becomes higher as drug administration time prolongs; （2） MIC≥5.0μg/mL may be taken as clinical drug resistance breakpoints according to MIC and clinical therapeutic effects evaluation; （3） TB patients with previous Prothionamide treatment history should take drug sensitive test for Prothionamide and follow rational, combinatorial principle of drug administration to avoid the production of drug resistance strains.