目的了解上海口岸结核分枝杆菌一线抗结核药物的耐药水平,为制定口岸传染性结核病防治策略提供依据,也为直接督导下的短程化疗(directly observed treatment short course,DOT)提供用药指导。方法针对2009年12月—2011年12月上海口岸出...目的了解上海口岸结核分枝杆菌一线抗结核药物的耐药水平,为制定口岸传染性结核病防治策略提供依据,也为直接督导下的短程化疗(directly observed treatment short course,DOT)提供用药指导。方法针对2009年12月—2011年12月上海口岸出入境人群中胸部影像学诊断疑似肺结核患者,采集其连续3d的晨痰分离培养结核分枝杆菌,用MGIT960培养法检测其一线抗结核药物(链霉素、异烟肼、利福平、乙胺丁醇、吡嗪酰胺)的耐药情况。结果共分离到结核分枝杆菌复合群38株,其中有11株至少对一种一线抗结核药物耐药,总耐药率为29.0%(11/38),接近国内报道数据31.7%,显著高于国际中位数12.2%(χ2=8.777,P=0.003)及香港地区14.4%(χ2=6.433,P=0.011)的耐药水平。单耐一种药物的耐药率为23.7%(9/38),其中单耐异烟肼5.3%(2/38);单耐链霉素5.3%(2/38);单耐吡嗪酰胺13.2%(5/38),未检出单耐利福平和单耐乙胺丁醇耐药株。耐多种药物的耐药率为5.3%(2/38),其中多耐药结核(mulitdrug resistanceTB,MDR-TB)2.6%(1/38),异烟肼合并乙胺丁醇和吡嗪酰胺耐药率2.6%(1/38)。结论上海口岸面临耐药性肺结核病传播风险。其一线抗结核药物总耐药率接近我国国内报道水平,但高于我国香港地区和国际中位数水平。单药物耐药特征为高吡嗪酰胺耐药率、低利福平和乙胺丁醇耐药率。多耐药率接近国内外报道水平。采用目前的DOT方案仍应有效。有必要建立口岸特色的传染性结核病防治措施,有效地维护公共卫生安全。展开更多
Background The epidemiological characteristics of drug-resistant tuberculosis （DR-TB） is fundamental to improving the prevention and control of DR-TB. Mutations in katG315 is thought to be the most predictive molecu...Background The epidemiological characteristics of drug-resistant tuberculosis （DR-TB） is fundamental to improving the prevention and control of DR-TB. Mutations in katG315 is thought to be the most predictive molecule markers for Isoniazid （INH） resistance in Mycobacterium tuberculosis （MTB）. However, mutations to these genes have not been thoroughly studied in China, and epidemiological evidence of their expression levels are especially lacking in the southwest of China, which has a high TB burden within the population. Methods MTB isolates were obtained from patients with active pulmonary tuberculosis at the TB dispensary and Chest hospital in Chongqing city between June 2003 and June 2006. Proportion methods were used to test the sensitivity to INH, RFP, SM and EMB of cultured MTB. A total of 100 MTB isolates were also randomly selected for analysis of the molecular mutation spectrum of katG by DNA sequencing. Results Totally 1 089 MTB isolates that completed positive sputum cultures and evaluated for their sensitivity to the four first-line drugs among 2 777 patients with TB. The prevalence of DR-TB and multi-drug resistant tuberculosis （MDR-TB） were 27.7% （302/1 089） and 7.3% （79/1 089）, respectively. The resistance to anti-TB drugs was found to be highest for SM （16.3%） and INH （14.0%）. There was also a significant increase in the prevalence of resistance to RFP and EMB （P〈0.01）, and an increase in MDR-TB between June 2003 and June 2004 and between July 2005 and June 2006. The total mutation rate of katG315 was 75＂5% （37/49） in INH-resistant MTB, and mutation sites included $315T, $315N and $315I with mutation rates of 81.1% （30/37）, 13.5% （5/37） and 5.4% （2/37）, respectively No katG315 mutants were found in any of the 48 INH-sensitive MTB. Our preliminary diagnostic results suggest that mutations in katG315 may potentially serve as molecular markers that can be used to diagnose the resistance to anti-TB drug of INH. Conclusion In the Chongqing, DR-TB and MDR-TB are increasing, and are becoming key problems for tuberculosis control. The use of katG315 mutations as potential molecule markers for drug resistance to INH may help improve patient treatment and decrease the spread of the disease展开更多
基金Supported by the National Natural Science Foundation of China(30700685)the Medical Science and Technology Research Project of Chongqing Municipal Health Bureau(2009-1-06)
文摘Background The epidemiological characteristics of drug-resistant tuberculosis （DR-TB） is fundamental to improving the prevention and control of DR-TB. Mutations in katG315 is thought to be the most predictive molecule markers for Isoniazid （INH） resistance in Mycobacterium tuberculosis （MTB）. However, mutations to these genes have not been thoroughly studied in China, and epidemiological evidence of their expression levels are especially lacking in the southwest of China, which has a high TB burden within the population. Methods MTB isolates were obtained from patients with active pulmonary tuberculosis at the TB dispensary and Chest hospital in Chongqing city between June 2003 and June 2006. Proportion methods were used to test the sensitivity to INH, RFP, SM and EMB of cultured MTB. A total of 100 MTB isolates were also randomly selected for analysis of the molecular mutation spectrum of katG by DNA sequencing. Results Totally 1 089 MTB isolates that completed positive sputum cultures and evaluated for their sensitivity to the four first-line drugs among 2 777 patients with TB. The prevalence of DR-TB and multi-drug resistant tuberculosis （MDR-TB） were 27.7% （302/1 089） and 7.3% （79/1 089）, respectively. The resistance to anti-TB drugs was found to be highest for SM （16.3%） and INH （14.0%）. There was also a significant increase in the prevalence of resistance to RFP and EMB （P〈0.01）, and an increase in MDR-TB between June 2003 and June 2004 and between July 2005 and June 2006. The total mutation rate of katG315 was 75＂5% （37/49） in INH-resistant MTB, and mutation sites included $315T, $315N and $315I with mutation rates of 81.1% （30/37）, 13.5% （5/37） and 5.4% （2/37）, respectively No katG315 mutants were found in any of the 48 INH-sensitive MTB. Our preliminary diagnostic results suggest that mutations in katG315 may potentially serve as molecular markers that can be used to diagnose the resistance to anti-TB drug of INH. Conclusion In the Chongqing, DR-TB and MDR-TB are increasing, and are becoming key problems for tuberculosis control. The use of katG315 mutations as potential molecule markers for drug resistance to INH may help improve patient treatment and decrease the spread of the disease
