初治耐多药肺结核患者采用初治标准方案治疗的前瞻性临床研究

Treatment of newly diagnosed multi-drug resistant pulmonary tuberculosis： a prospective clinical study

目的探讨一线抗结核药物在初治耐多药肺结核（MDR-PTB）的治疗中是否仍有应用的空间，为正确处理初治MDR-PTB提供依据。方法对2011年1月至2013年12月上海市所有登记的肺结核患者（共19042例）采用“全面筛查”方式，共发现168例初治MDR-PTB患者，将具有上海市户籍或工作居住证并签订了知情同意书的114例患者纳入本次研究。经上海市MDR-PTB防治专家组分析讨论后对所有研究对象进行初治标准方案治疗。以患者强化期治疗不同效果进行分组，显效者继续完成12H—R-Z-E方案治疗（简称“标准治疗组”），无效者则给予耐多药方案治疗（简称“耐多药治疗组”）24个月，标准治疗组治疗成功的患者在疗程结束后每2个月随访1次，至信息采集截止时平均随访了16个月。观察两组治疗成功率、患者失访率、死亡率、药物不良反应发生率。结果58例强化期显效者继续给予12H—R-Z-E方案治疗，56例无效者给予耐多药方案治疗，基本方案为6Cm-Lfx-Pto-PAS-z／18Lfx-Pto—PAS-Z。标准治疗组和耐多药治疗组的治疗成功率、患者失访率分别为69．O％（40／58）和67。9％（38／56）、5.2％（3／58）和7．1％（4／56），差异均无统计学意义（χ2=0．01，P=0．899；χ2=0．66，P=0．192）；标准治疗组和耐多药治疗组的死亡率、药物不良反应发生率分别为0．0％和10．7％（6／56）、13．8％（8／58）和53．6％（30／56），差异均有统计学意义（x。一6．56，P=0．010；：（。一20．29，P〈O．01）。其中标准治疗组中15例治疗失败者转入耐多药治疗组治疗，其治疗成功率为73．3％（11／15）、死亡率6．7％（1／18）；标准治疗组40例治愈者有2例在疗程结束6个月后复发，经药物敏感性试验再次确诊为MDR-PTB。结论初治MDR-PTB患者采用12HR-Z-E标准化疗方案治疗在治疗成功率、患者失访率方面与“延迟”进行耐多药治疗（初始未采用耐多药治疗方案，无效后使用）的患者差异无统计学意义，说明一线抗结核药物治疗初治MDR-PTB仍有一定的空间，延迟进行耐多药方案治疗不影响治疗效果，且分类治疗有助于患者减少药物不良反应和死亡率。

Objective To discuss whether first-line anti-tuberculosis drugs could still be used to treat newly diagnosed multi-drug resistant pulmonary tuberculosis （MDR-PTB） and to provide evidence for treatment of newly- diagnosed MDR-PTB correctly. Methods From January 2011 to December 2013, all 19 042 registered PTB patients in Shanghai were screened. 168 newly diagnosed MDR-PTB patients were found, among whom 114 patients who has household registration in Shanghai or temporary residential permit of Shanghai were enrolled in the study and their informed consent had signed. Standard original chemotherapy regimen was given for each MDR-PTB patient designed by the expert panel. The group was divided by the treatment effect in the intensive phase. The standard group with 12H-R-Z-E regimen had a favorable treatment reaction. And the MDR-PTB group with 6Cm-Lfx-Pto-PAS-Z/18Lfx-Pto-PAS-Z had a unfavorable treatment reaction at the end of the intensive phase. In standard treatment group, patients with a favorable treatment were followed up every 2 months after the period of treatment, and the average follow-up period was 16 months. The success rate of treatment, the loss rate of patients, mortality rate and incidence of adverse drug reactions were observed in 2 groups. Results The success rate of treatment and the loss rate of patients in two groups was 69.0K （40/58）, 67.90/oo （38/56）and 5.2 （3/58）, 7.1% （4/56）, respectively. The difference was not statistically significant （Zz=0.01,P=0. 899;Z2=0.66,P=0. 192）. The mor- tality rate and incidence of adverse drug reactions in two groups was 0.0%, 10.7% （6/56） and 13.8% （8/58）, 53.6% （30/56）, respectively. The difference was statistically significant （χ2 = 6.56, P = 0. 010 ;χ2 = 20.29, P〈0.01）. 15 （25.9%） patients in standard group were transferred to MDR-PTB regimen. Out of them, 73.3% （11/15） were cured,one patient died. Relapse happened in 2 patients of standard group 6 months after the end of the course of treatment with DST result of MDR-PTB again. Conclusion First-line drugs can still be used in the treat- ment of some newly diagnosed MDR-PTB patients because of the similar treatment effect in first-line drugs and de- layed treatment. The classification treatment of newly diagnosed MDR-PTB patients make patients get reasonable treatment, reduce unnecessary adverse drug reactions and improve patient compliance.