涂阳肺结核患者243例耐药特征分析
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摘要
目的分析243例涂阳肺结核患者的耐药情况,为制定合理的耐药结核病治疗方案提供科学依据。方法选取2016年1—12月安徽省胸科医院收治的243例涂阳肺结核患者。经痰分离培养并进行10种抗结核药物(异烟肼、利福平、链霉素、乙胺丁醇、左氧氟沙星、阿米卡星、卷曲霉素、丙硫异烟胺、对氨基水杨酸钠以及利福喷丁)的药物敏感性试验,对其结果进行分析。结果所有患者的任一耐药率为41. 6%(101/243)。复治患者任一耐药、耐多药、对一线抗结核药物耐药及对二线抗结核药物耐药的比率高于初治患者[68. 7%(68/99)比22. 9%(33/144)、33. 3%(33/99)比2. 8%(4/144)、63. 6%(63/99)比14. 6%(21/144)、63. 6%(63/99)比18. 1%(26/144)],差异均有统计学意义(均P <0. 001)。耐一线抗结核药物患者84例,其中耐多药患者37例,耐药率由高到低依次为利福平>链霉素>异烟肼>乙胺丁醇。耐二线抗结核药物患者89例,对各药的耐药率由高到低依次为利福喷丁>丙硫异烟胺=左氧氟沙星>阿米卡星>卷曲霉素>对氨基水杨酸钠。结论结核病尤其是耐药结核病形势不容乐观,乙胺丁醇、卷曲霉素、阿米卡星、对氨基水杨酸钠仍有很大的临床抗结核价值,应注意复治肺结核方案的合理制定,遏制耐药结核病流行。
Objective To analyze the drug resistance of sputum smear-positive pulmonary tuberculosis in243 patients and provide scientific evidence for reasonable treatment of drug-resistant tuberculosis. Methods From January to December 2016,243 patients with sputum smear-positive pulmonary tuberculosis were enrolled at Anhui Chest Hospital. Drug sensitivity tests of 10 anti-tuberculosis drugs( isoniazid,rifampicin,streptomycin,ethambutol,levofloxacin,amikacin,capreomycin,protionamide,sodium aminosalicylate and rifametine) were conducted after sputum separation and culture. Results of drug resistance were analyzed. Results Drug resistance rate of all patients was 41. 6%( 101/243). Rates of drug resistance,multi-drug resistance,first-line anti-tuberculosis drug resistance and second-line anti-tuberculosis drug resistance in retreated patients were higher than those in newly diagnosed patients[68. 7%( 68/99) vs 22. 9%( 33/144),33. 3%( 33/99) vs 2. 8%( 4/144),63. 6%( 63/99) vs14. 6%( 21/144),63. 6%( 63/99) vs 18. 1%( 26/144) ]( all P < 0. 001). Eighty-four patients were resistant to first-line anti-tuberculosis drugs,among them 37 patients presented multi-drug resistance; the order of resistance rates was rifampicin > streptomycin > isoniazid > ethambutol. Eighty-nine patients were resistant to second-line anti-tuberculosis drugs; the order of resistance rates was rifapentine > protionamide = levofloxacin > amikacin >capreomycin > sodium aminosalicylate. Conclusion Tuberculosis,especially drug-resistant tuberculosis is a big clinical problem; ethambutol,capreomycin,amikacin and sodium aminosalicylate show significant anti-tuberculous values; the drug resistance situation of retreatment of tuberculosis is severe.
Objective To analyze the drug resistance of sputum smear-positive pulmonary tuberculosis in243 patients and provide scientific evidence for reasonable treatment of drug-resistant tuberculosis. Methods From January to December 2016,243 patients with sputum smear-positive pulmonary tuberculosis were enrolled at Anhui Chest Hospital. Drug sensitivity tests of 10 anti-tuberculosis drugs( isoniazid,rifampicin,streptomycin,ethambutol,levofloxacin,amikacin,capreomycin,protionamide,sodium aminosalicylate and rifametine) were conducted after sputum separation and culture. Results of drug resistance were analyzed. Results Drug resistance rate of all patients was 41. 6%( 101/243). Rates of drug resistance,multi-drug resistance,first-line anti-tuberculosis drug resistance and second-line anti-tuberculosis drug resistance in retreated patients were higher than those in newly diagnosed patients[68. 7%( 68/99) vs 22. 9%( 33/144),33. 3%( 33/99) vs 2. 8%( 4/144),63. 6%( 63/99) vs14. 6%( 21/144),63. 6%( 63/99) vs 18. 1%( 26/144) ]( all P < 0. 001). Eighty-four patients were resistant to first-line anti-tuberculosis drugs,among them 37 patients presented multi-drug resistance; the order of resistance rates was rifampicin > streptomycin > isoniazid > ethambutol. Eighty-nine patients were resistant to second-line anti-tuberculosis drugs; the order of resistance rates was rifapentine > protionamide = levofloxacin > amikacin >capreomycin > sodium aminosalicylate. Conclusion Tuberculosis,especially drug-resistant tuberculosis is a big clinical problem; ethambutol,capreomycin,amikacin and sodium aminosalicylate show significant anti-tuberculous values; the drug resistance situation of retreatment of tuberculosis is severe.
引文
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[3]Gegia M,Kalandadze I,Kempker RR,et al.Adjunctive surgery improves treatment outcomes among patients with multidrug resistant and extensively drug resistant tuberculosis[J].Int JInfect Dis,2012,16(5):e391-396.DOI:10.1016/j.ijid.2011.12.018.
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[5]周云,刘瑞,杜永国,等.海南省219株耐药结核分枝杆菌药敏试验结果分析[J].现代预防医学,2017,44(19):3640-3644.Zhou Y,Liu R,Du YG,et al.Drug sensitivity test results of 219drug-resistant mycobacterium tuberculosis,Hainan[J].Modern Preventive Medicine,2017,44(19):3640-3644.
[6]张培元.肺结核诊断和治疗指南[J].中华结核和呼吸杂志,2001,24(2):70-74.DOI:10.3760/j:issn:1001-0939.2001.02.002.Zhang PY.Guidelines for diagnosis and treatment of tuberculosis[J].Chinese Journal of Tuberculosis and Respiratory Diseases,2001,24(2):70-74.DOI:10.3760/j:issn:1001-0939.2001.02.002.
[7]赵雁林.结核病实验室诊断技术培训教程[M].北京:人民卫生出版社,2014:54-73.Zhao YL.Training course for laboratory diagnosis technology of tuberculosis[M].Beijing:People's Health Publishing House,2014:54-73.
[8]中国防痨协会.耐药结核病化学治疗指南(2015)[J].中国防痨杂志,2015,37(5):421-469.DOI:10.3969/j.issn.1000-6621.2015.05.001.Anti-Tuberculosis Association of China.Guideline for chemotherapy of drug-resistant tuberculosis(2015)[J].Chinese Journal of Antituberculosis,2015,37(5):421-469.DOI:10.3969/j.issn.1000-6621.2015.05.001.
[9]杨松,陈耀凯.结核分枝杆菌基因多样性及其耐药特点的研究进展[J].临床内科杂志,2018,35(3):152-154.DOI:10.3969/j.issn.1001-9057.2018.03.002.Yang S,Chen YK.Advances in gene diversity and drug resistance of mycobacterium tuberculosis[J].Journal of Clinical Internal Medicine,2018,35(3):152-154.DOI:10.3969/j.issn.1001-9057.2018.03.002.
[10]中华人民共和国卫生部.全国结核病耐药性基线调查报告(2007~2008年)[M].北京:人民卫生出版社,2010:24-38.Ministry of health of the People's Republic of China.Baseline survey of tuberculosis resistance in China(2007-2008)[M].Beijing:People's Health Publishing House,2010:24-38.
[11]车洋,于梅,许国章,等.332例复治肺结核患者一线抗结核药物耐药情况分析[J].中国卫生检验杂志,2014,24(23):3481-3483.Che Y,Yu M,Xu GZ,et al.Drug-resistance analysis of clinical anti-tuberculosis drugs for 332 retreatment tuberculosis patients[J].Chinese Journal of Health Laboratory Technology,2014,24(23):3481-3483.
[12]Chand KS,Manchanda RK,Mittal R,et al.Homeopathic treatment in addition to standard care in multi drug resistant pulmonary tuberculosis:a randomized,double blind,placebo controlled clinical trial[J].Homeopathy,2014,103(2):97-107.DOI:10.1016/j.homp.2013.12.003.
[13]Boehme CC,Nicol MP,Nabeta P,et al.Feasibility,diagnostic accuracy,and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance:a multicentre implementation study[J].Lancet,2011,377(9776):1495-1505.DOI:10.1016/S0140-6736(11)60438-8.
[14]Kurbaniyazova G,Joncevska M,Kalon S,et al.Results of XpertMTB/RIF implementation in Kyrgyzstan[J].Int J Tuberc Lung Dis,2017,21(3):333-337.DOI:10.5588/ijtld.16.0191.
[15]Huang H,Zhang Y,Li S,et al.Rifampicin resistance and multidrug-resistant tuberculosis detection using Xpert MTB/RIF in wuhan,China:a retrospective study[J].Microb Drug Resist,2018,24(5):675-679.DOI:10.1089/mdr.2017.0114.
[16]张志平,李贤相,文育锋,等.342例痰培养阳性肺结核菌株耐药特征分析[J].现代预防医学,2015,42(3):522-525.Zhang ZP,Li XX,Wen YF,et al.Analysis of drug resistance characteristic of 342 sputum culture positive pulmonary tuberculosis[J].Modern Preventive Medicine,2015,42(3):522-525.
[2]全国第五次结核病流行病学抽样调查技术指导组,全国第五次结核病流行病学抽样调查办公室.2010年全国第五次结核病流行病学抽样调查报告[J].中国防痨杂志,2012,34(8):485-508.The fifth national tuberculosis epidemiological sampling survey technical guidance group,The fifth national tuberculosis epidemiological sampling survey office.The fifth national tuberculosis epidemiological survey in 2010[J].Chinese Journal of Antituberculosis,2012,34(8):485-508.
[3]Gegia M,Kalandadze I,Kempker RR,et al.Adjunctive surgery improves treatment outcomes among patients with multidrug resistant and extensively drug resistant tuberculosis[J].Int JInfect Dis,2012,16(5):e391-396.DOI:10.1016/j.ijid.2011.12.018.
[4]World Health Organization.Global tuberculosis report 2014[R].Geneva:World Health Organization,2014:126.
[5]周云,刘瑞,杜永国,等.海南省219株耐药结核分枝杆菌药敏试验结果分析[J].现代预防医学,2017,44(19):3640-3644.Zhou Y,Liu R,Du YG,et al.Drug sensitivity test results of 219drug-resistant mycobacterium tuberculosis,Hainan[J].Modern Preventive Medicine,2017,44(19):3640-3644.
[6]张培元.肺结核诊断和治疗指南[J].中华结核和呼吸杂志,2001,24(2):70-74.DOI:10.3760/j:issn:1001-0939.2001.02.002.Zhang PY.Guidelines for diagnosis and treatment of tuberculosis[J].Chinese Journal of Tuberculosis and Respiratory Diseases,2001,24(2):70-74.DOI:10.3760/j:issn:1001-0939.2001.02.002.
[7]赵雁林.结核病实验室诊断技术培训教程[M].北京:人民卫生出版社,2014:54-73.Zhao YL.Training course for laboratory diagnosis technology of tuberculosis[M].Beijing:People's Health Publishing House,2014:54-73.
[8]中国防痨协会.耐药结核病化学治疗指南(2015)[J].中国防痨杂志,2015,37(5):421-469.DOI:10.3969/j.issn.1000-6621.2015.05.001.Anti-Tuberculosis Association of China.Guideline for chemotherapy of drug-resistant tuberculosis(2015)[J].Chinese Journal of Antituberculosis,2015,37(5):421-469.DOI:10.3969/j.issn.1000-6621.2015.05.001.
[9]杨松,陈耀凯.结核分枝杆菌基因多样性及其耐药特点的研究进展[J].临床内科杂志,2018,35(3):152-154.DOI:10.3969/j.issn.1001-9057.2018.03.002.Yang S,Chen YK.Advances in gene diversity and drug resistance of mycobacterium tuberculosis[J].Journal of Clinical Internal Medicine,2018,35(3):152-154.DOI:10.3969/j.issn.1001-9057.2018.03.002.
[10]中华人民共和国卫生部.全国结核病耐药性基线调查报告(2007~2008年)[M].北京:人民卫生出版社,2010:24-38.Ministry of health of the People's Republic of China.Baseline survey of tuberculosis resistance in China(2007-2008)[M].Beijing:People's Health Publishing House,2010:24-38.
[11]车洋,于梅,许国章,等.332例复治肺结核患者一线抗结核药物耐药情况分析[J].中国卫生检验杂志,2014,24(23):3481-3483.Che Y,Yu M,Xu GZ,et al.Drug-resistance analysis of clinical anti-tuberculosis drugs for 332 retreatment tuberculosis patients[J].Chinese Journal of Health Laboratory Technology,2014,24(23):3481-3483.
[12]Chand KS,Manchanda RK,Mittal R,et al.Homeopathic treatment in addition to standard care in multi drug resistant pulmonary tuberculosis:a randomized,double blind,placebo controlled clinical trial[J].Homeopathy,2014,103(2):97-107.DOI:10.1016/j.homp.2013.12.003.
[13]Boehme CC,Nicol MP,Nabeta P,et al.Feasibility,diagnostic accuracy,and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance:a multicentre implementation study[J].Lancet,2011,377(9776):1495-1505.DOI:10.1016/S0140-6736(11)60438-8.
[14]Kurbaniyazova G,Joncevska M,Kalon S,et al.Results of XpertMTB/RIF implementation in Kyrgyzstan[J].Int J Tuberc Lung Dis,2017,21(3):333-337.DOI:10.5588/ijtld.16.0191.
[15]Huang H,Zhang Y,Li S,et al.Rifampicin resistance and multidrug-resistant tuberculosis detection using Xpert MTB/RIF in wuhan,China:a retrospective study[J].Microb Drug Resist,2018,24(5):675-679.DOI:10.1089/mdr.2017.0114.
[16]张志平,李贤相,文育锋,等.342例痰培养阳性肺结核菌株耐药特征分析[J].现代预防医学,2015,42(3):522-525.Zhang ZP,Li XX,Wen YF,et al.Analysis of drug resistance characteristic of 342 sputum culture positive pulmonary tuberculosis[J].Modern Preventive Medicine,2015,42(3):522-525.