湖南省肺结核四种一线抗结核药物耐药特征及影响因素研究

目的 分析湖南省肺结核四种一线抗结核药物耐药特征及其影响因素,为防治耐药结核病提供科学依据。方法 收集2012-2016年湖南省胸科医院住院诊疗的所有肺结核患者病历信息,以菌型鉴定证实为结核分枝杆菌且进行了一线4种抗结核药物(异烟肼、利福平、链霉素、乙胺丁醇)敏感度测试者为研究对象,运用单因素和多因素分析方法研究肺结核的耐药特征及其影响因素。结果 2012-2016年共有11 486例患者纳入研究,其中,男性8 081例(70.4%),女性3 405(29.6%);平均年龄(44.6±14.5)岁;户籍以农村患者为主,共7 816例(68.0%),城市3 670例(32.0%);职业以农民为主,7 183例(62.5%)。肺结核总耐药率为30.6%,其中单耐药率为7.0%、耐多药率(MDR-TB)16.4%和多耐药率为7.2%;对利福平、异烟肼、链霉素和乙胺丁醇的总耐药率分别为22.3%、20.8%、8.5%和15.8%;对利福平、异烟肼、链霉素和乙胺丁醇单耐药率分别为1.9%、1.9%、1.4%和1.8%。湘西、湘北、湘中等地区的耐药率及耐多药率高于其他地区(χ²=36.295,P=0.000 1;χ²=50.970,P=0.000 1)。2012-2016年各年份耐药率分别为35.2%、32.0%、34.4%、27.7%、24.7%,总体呈下降趋势(χ²=91.792,P=0.000 1),耐多药率分别为18.9%、17.1%、18,5%、13.8%、14.3,总体呈下降趋势(χ²=60.933,P=0.000 1)。多因素Logistic回归分析结果显示,影响结核病耐药及耐多药产生的因素包括男性、21~60岁、农村、复治、职业为农民、湘西、湘北、湘中等。最主要的因素是治疗分类,复治患者发生耐药和耐多药的危险性是初治的4.231倍(95%CI: 3.855-4.643)和5.608倍(95%CI: 5.040-6.240)。结论 加强对农村地区、男性、职业为农民、年龄在21~60岁之间、复治的患者的治疗与管理,是预防和控制耐药及耐多药结核病产生的关键。

Retrospective study on the resistance characteristics and associated factors of four first-line anti-tuberculosis drugs in Hunan Province,China

In this study, we aimed to determine the epidemiological trends and associated factors of pulmonary drug resistance of tuberculosis in Hunan Province. Data were collected from the medical records of pulmonary tuberculosis patients in Hunan Chest Hospital, from the Hospital Management Information System (HMIS), during the period of 2012 to 2016. Hunan Chest Hospital is designed to provide diagnosis and treatment service for patients with lung diseases including TB and MDR-TB who are referred from the province. All patients diagnosed with drug resistance of tuberculosis by culture and drug susceptibility test in the hospital were included in this study. Univariate and multivariate logistic regression models were fitted to identify factors associated with drug resistance of tuberculosis. Results showed that a total of 11 486 patients who were registered in the hospital from 2012 to 2016 were included in the study. The majority of patients were male 8 081 (70.4%), female 3 405 (29.6%) and people lived in the rural area (68%). The mean age of the patients was 44.6 years (SD ±14.5 years). The overall prevalence of any type of drug resistance of tuberculosis was 30.6%. Of these, 7% were mono-drug resistant to tuberculosis, 16.4% were multidrug-resistant to tuberculosis (MDR-TB), and 7.2% were poly-drug resistant to tuberculosis. The prevalence of drug resistant to tuberculosis for first line anti-TB drug were 22.3% for rifampicin, 20.8% for isoniazid, 8.5% for streptomycin and 15.8% for ethambutol. The mono-resistance prevalence of rifampicin, isoniazid, streptomycin and ethambutol were 1.9%, 1.9%, 1.4% and 1.8% respectively. The drug resistance rate and multi-drug resistance rate in the west, the north and the middle of Hunan, were higher than those in other areas (χ²=36.295,P=0.000 1;χ²=50.970,P=0.000 1). Drug resistance rates were 35.2%, 32.0%, 34.4%, 27.7%, 24.7% from 2012 to 2016, (χ²=91.792, P=0.000 1), multi-drug resistance rate were 18.9%, 17.1%, 18,5%, 13.8%, 14.3%, (χ²=60.933, P=0.000 1). In the univariate analysis, male, age 21-60 years, household registration in rural areas, retreatment, farmers and living in the west, the north and the middle of Hunan, were significantly associated with any type of drug resistance and multidrug resistance of tuberculosis. In the multivariate analysis, retreatment was remained an intendments risk factors for any type of drug resistance of tuberculosis 4.231 (95% CI: 3.855-4.643), multi-drug resistance of tuberculosis 5.608 (95% CI: 5.040-6.240). The prevalence of drug resistance of tuberculosis including MDR-TB was high in hospitalized pulmonary tuberculosis patients in Hunan Province. The trends of drug resistance of tuberculosis gradually decreased from 2012 to 2016. Age, gender, residence, treatment history, and occupations were identified as factors associated with any type of drug resistance of tuberculosis, and MDR-TB. Measures should be taken to strengthen the prevention and control of drug resistance of tuberculosis.