含异烟肼耐药的耐药结核病临床特点和治疗方案的回顾性队列分析

A retrospective cohort study of clinical characteristics and treatment regimens of drug-resistant tuberculosis containing isoniazid-resistance

目的回顾性分析含异烟肼耐药的耐药结核病[(Hr)DR-TB]患者的临床特点和治疗方案,为其临床诊疗和临床研究提供证据。方法收集并分析2011年1月至2016年12月深圳市第三人民医院619例经表现型药物敏感性检测(pDST)确诊为(Hr)DR-TB的患者人口学数据、抗结核治疗史、结核分枝杆菌(Mtb)药物敏感性检测(DST)结果、耐药谱变迁、治疗方案和结局等信息。结果①619例(Hr)DR-TB患者中,Hr-TB患者232例(37.5%),耐多药结核病(MDR-TB)患者387例(62.5%);在初治病例中两者比例为49.7%和50.3%,在复治病例中两者比例为22.8%和77.2%。抗结核药物从敏感变成耐药者占10.8%;从耐药变成敏感者占7.4%。②在235例Hr-TB中,合并左氧氟沙星耐药者20例(8.5%),合并乙胺丁醇耐药者21例(8.9%)。对左氧氟沙星敏感者,初始依旧使用异烟肼的有162例(80.5%);对左氧氟沙星耐药者,初始依旧使用左氧氟沙星的有14例(70.0%)。在表现型药物敏感性检测(pDST)报告后,大部分病例并没有调整抗结核方案(86.4%,203/235)。在治疗结局方面,失访者达到71.5%(168/235);初治患者的治疗成功率高于复治患者(29.8%比16.4%,P<0.01)。结论 (Hr)DR-TB患者以青中年居多,合并利福平耐药者多,治疗中耐药谱容易变迁。Hr-TB治疗过程中较少根据DST调整治疗方案,且70%以上病例失访,需重视(Hr)DR-TB尤其是Hr-TB的规范诊疗。

Objective To analyze the clinical characteristics and treatment regimens of drug-resistant tuberculosis containingisoniazid-resistance (Hr)DR-TB patients,and provide evidence for clinical practice and further research.Methods We retrospectively enrolled patients with (Hr)DR-TB,including Hr-TB and multidrug-resistant tuberculosis (MDR-TB) during January 2011 to December 2016 in Shenzhen Third People’s Hospital,collected the demographic data,history of anti-tuberculosis treatment,phenotypic drug susceptibility testing (pDST) results of Mycobacterium tuberculosis and the changes of pDST,treatment regimens and adjustment strategy,treatment outcomes,and divided these data into new cases and retreated cases for comparative analysis.Results ①There are 37.5% (232/619) of Hr-TB and 62.5% (387/619) of MDR-TB in total,49.7% and 50.3% in new cases,and 22.8% and 77.2% in retreated cases.Some patients experienced changes in the drug resistance spectrum during anti-tuberculosis treatment or after TB recurrence.10.8% (67/619) of anti-tuberculosis drugs changed from drug-susceptible to drug-resistant.7.4% (46/619) changed from drug-resistant to drug-susceptible.②Among 235 cases of Hr-TB,according to the pDST results,8.5% (20/235) of patients with levofloxacin resistance and 8.9% (21/235) of patients with ethambutol resistance were found.Among the retreated cases,levofloxacin-resistant patients accounted for 20.9% (14/67),which was more than that in new cases (20.9% vs 3.6%,P>0.05).Among those who were sensitive to levofloxacin,80.5% (167/215) used isoniazid in the initial regimen.Among those resistant to levofloxacin,70% (14/20) used levofloxacin.After the pDST was reported,most cases (86.4%,203/235) ignored the results and did not adjust their regimens.In terms of treatment outcome,71.5% (168/235) were lost to follow-up,and 26.4% (62/235) maintained in the cohort.The treatment success rate of newly cases was higher than that of retreated cases (29.8%,50/168 vs 16.4%,11/67,P<0.01).Conclusion The most of (Hr)DR-TB patients were young and middle-aged men,and most of them were combined with rifampicin resistance.The drug resistance spectrum was easy to change during treatment.During the treatment of HR-TB,the treatment was rarely adjusted according to drug sensitivity,and more than 70% of cases were lost to follow-up.Attention should be paid to the standardized diagnosis and treatment of (HR) Dr-TB,especially Hr-TB.