肺结核病原体和易感因素及结核分枝杆菌优势耐药谱分析

目的 了解县镇地区肺结核流行现状及其易感因素、结核分枝杆菌耐药谱和优势耐药组合模式方法 采用罗氏培养基和PNB/TCH生长试验,对杭州市周边7个县镇临床诊断为肺结核的2 840例初治和712例复治患者抗酸染色阳性痰标本进行分枝杆菌分离培养和菌种鉴定。采用浓度比例法,检测3 152株结核分枝杆菌对链霉素(SM)、异烟肼(INH)、利福平(RIF)、乙胺丁醇(EMB)、氧氟沙星(OFX)和卡那霉素(KM)的敏感性。采用统计学方法分析结核分枝杆菌优势耐药模式以及肺结核易感因素结果 3 552株分枝杆菌中,88.7%(3 152/3 552)为结核分枝杆菌,11.3%(400/3 552)为非结核分枝杆菌,复治患者非结核分枝杆菌感染率(23.7%)显著高于初治患者(8.1%)(χ²=138.67,P<0.05)。3 152株结核分枝杆菌对6种抗结核药物总耐药率为25.1%,对一线抗结核药物耐药、耐多药和广泛耐药率分别为15.9%、4.6%和0.2%,其中SM(χ²=50.40, P<0.05)和INH耐药率较高(χ²=47.81, P<0.05)。结核分枝杆菌有35种耐药谱,优势耐药组合模式分别为INH+SM(χ²=19.19,P<0.05)、INH+RFP+SM(χ²=24.85,P<0.05)和IHN+RFP+SM+EMB(χ²=20.11,P<0.05)。来自复治患者的结核分枝杆菌总耐药、一线抗结核药物耐药、耐多药和广泛耐药率(38.3%、36.1%、14.0%和0.9%)均显著高于初治患者(22.3%、19.3%、2.7%和0.04%)(P<0.05)。本地户籍60岁以上男性农民肺结核发病率显著较高(χ²=1 435.29,P<0.05)结论 本县镇地区肺结核疫情防控形势依然严峻,老年男性农民是肺结核易感人群,复治肺结核患者非结核分枝杆菌感染率以及结核分枝杆菌耐药性显著高于初治肺结核患者,提示县镇地区肺结核患者抗结核药物规范化治疗有待加强。

Pathogens and risk factors of pulmonary tuberculosis and predominant resistance spectra of Mycobacterium tuberculosis

The aim of this study is to investigate the current prevailing situation and risk factors of pulmonary tuberculosis in counties and towns as well as analyze the drug resistance spectra and predominant resistance combination modes of Mycobacteria tuberculosis. The strains of Mycobacteria in sputum samples from 2 840 initial treatment and 712 retreatment pulmonary patients clinically diagnosed as tuberculosis in 7 small cities and towns near Hangzhou isolated using Lwenstein-Jensen medium and the isolates were then identified by PNB/TCH growth test. The susceptibility of 3 152 Mycobacterium tuberculosis isolates against streptomycin (SM), isoniazide (INH), rifampicin (RIF), ethambutol (EMB), ofloxacin (OFX) and kanamycin (KM) was detected by concentration proportional method. The predominant resistance modes of Mycobacterium tuberculosis isolates and risk factors of pulmonary tuberculosis were analyzed by statistical method. In the 3 552 isolates of mycobacteria, 88.7% (3 152/3 552) and 11.3% (400/3 552) of the strains were identified as Mycobacterium tuberculosis and nontuberculosis mycobacteria, respectively, and the infection rate of nontuberculosis mycobacteria in the retreatment patients (23.7%) was significantly higher than that in the initial treatment patients (8.1%) (χ²=138.67, P<0.05). The total drug resistance rates of 3 152 Mycobacterium tuberculosis isolates against the six anti-tuberculosis drugs was 25.1% while the first line anti-tuberculosis drug resistance, multiple drug resistance and extensive drug resistance rates were 15.9%, 4.6% and 0.2%, respectively. The resistance rate against SM(χ²=50.40, P<0.05) or INH(χ²=47.81, P<0.05) was significantly higher than that of the other four anti-tuberculosis drugs. The Mycobacterium tuberculosis isolates presented 35 drug-resistant spectra and the predominant resistance combination modes were INH+SM (χ²=19.19, P<0.05), INH+RFP+SM (χ²=24.85, P<0.05) and IHN+RFP+SM+EMB (χ²= 20.11, P<0.05). The total resistance, first line anti-tuberculosis drug resistance, multiple drug resistance and extensive drug resistance rates of the Mycobacterium tuberculosis isolates from the retreatment patients (38.3%, 36.1%, 14.0% and 0.9%) were significantly higher than those from the initial treatment patients (22.3%, 19.3%, 2.7% and 0.04%) (P<0.05). The local male peasants over 60 years old presented a significant higher pulmonary tuberculosis rate (χ²=1 435.29,P<0.05). All the data indicate that the situation of pulmonary tuberculosis prevention and control in the counties and towns is still severe and old male peasants are the susceptible population of pulmonary tuberculosis. The infect rate of nontuberculosis mycobacteria in the retreatment pulmonary tuberculosis patients is significantly higher than that in the initial treatment pulmonary tuberculosis patients, which indicates that the normalized anti-tuberculosis drug therapy of pulmonary tuberculosis patients in these regions needs to be improved.