用户名: 密码: 验证码:
新疆喀什地区肺结核耐药状况及影响因素分析
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:了解新疆喀什地区结核分支杆菌耐药现状、探讨耐药的影响因素,为更好的制定耐药结核病控制及预防策略提供理论依据。方法:收集2010年6月-2010年12月在喀什胸科医院住院诊治的全部新发及复治痰结核分支杆菌涂片阳性的肺结核患者的痰标本,用改良酸性罗氏培养基培养,按绝对浓度法对结核菌株经PNB、TCH鉴别分型136株结核分枝杆菌作为药物敏感试验对象;应用比例法对全部培养阳性标本进行8种抗结核药物(异烟肼,利福平,链霉素,乙胺丁醇,氧氟沙星,卷曲霉素,卡那霉素,阿米卡星)的耐药性检测,回顾性收集患者临床资料。结果:136株结核分离株可用,109例(80.15%)为人结核分枝杆菌,26例(19.12%)为牛结核分支杆菌,1例(0.74%)为非结核分枝杆菌。研究对象中有56例来自初治肺结核患者,80例来自复治肺结核患者,患者总耐药率为32.35%,初始耐药率28.57%,获得性耐药率为35.00%,总耐多药率为6.62%,初始耐多药率为3.57%,获得性耐多药率8.75%,无广泛耐药发生。8种耐任一抗结核药物的耐药率由高到低分别为H(22.79%).S(11.76%).R(8.82%).E(6.62%).Ofx(2.94%).Cm(2.94%).Km(0.74%).Am(0.74%)。初治结核病人对异烟肼、链霉素、利福平、乙胺丁醇、氧氟沙星、卷曲霉素、卡那霉素、阿米卡星这8种抗结核药物的耐药率分别为:17.86%、16.07%、3.57%、5.36%、3.57%、0%、0%、0%;复制患者对以上8种抗结核药物的耐药率分别为:26.25%.8.75%.12.50%.7.50%.2.50%.1.25%.1.25%.耐1种.2种.3种和4种以上一线药物的初始耐药率和获得性耐药率分别为17.86%、3.57%、5.36%、0%和15.00%、13.75%,3.75%、0%,初治及复治患者的耐2药率差异有统计学意义。不同年龄组耐药率差异无显著性;不同性别、年龄组初始耐药差异无显著性。经单因素非条件logistic回归分析,不同性别、不同文化程度、不同居住地、不同职业、有无慢性病史、有无空洞、化疗史、有无延误对耐药率的影响差异无统计学意义(P>0.05)。结论:患结核杆菌的以人型结核杆菌最为常见。新疆喀什地区耐药结核病的发生率较高,耐药现状引起重视。本次研究表明8种抗结核药物均有一定程度的耐药,抗结核药物中耐药率排序前三位的分别是异烟肼、链霉素、利福平。性别、年龄对初治耐药率无影响。常规结核分支杆菌培养及药敏试验可以科学合理的指导临床用药,对于控制结核病的传播有极其重要的流行病学意义。
Objective:study the status of the drug resistence of mycobacterium tuberculosis, discuss factor influencing drug resistence to mycobacterium tuberculosis in the city of kashi, xinjiang province, and provide theoretical evidence for tuberculosis control and prevent strategy in the future. Methods:136 sputum specimens of smear positive, were collect from all in-patient cases of tuberculosis from June to December 2010 in KaShi Chest Hospital, Ameliorative Lowenstein-Jensen culture medium was used to detect bacillus, positive specimen o f pulmonary tuberculosis by typing using PNB and TCH. To tally 136 samples were confirmed to be positive by culturing. Drug susceptibility test against streptomycin(INH, SM, RFP, EB, OFX, Km, Amk, Cm), was conducted by the proportion method, and collect the chinical data by retrospective method.Results:Among 136 sputum specimens containing Mycobacterium tuberculosis,109 strains (8015%)were identified to human pulmonary tuberculosis; 26 strains (19.12%) were identified to bovine pulmonary tuberculosis; strain(0.74%) non-tuberculosis mycobacteria.56 were from patients of primary tuberculosis, while 80 from patients of recurrent tuberculosis.the rate of total drug resistance was32.35%, the rate of initial drug resistance was28.57%, the rate of acquired drug resistance was35.00%, the rate of total multidrug resistance was6.62%, the rate of initial drug multidrug resistance was3.57%, and the rate of acquired drug multidrug resistance was8.75%, and no XDR-TB was found in this study. Any resistancetoINH, SM, RFP, EMB, OFX, Cm, Km, Amkwas22.79%,11.76%,8.82%, 6.62%,2.94%,2.94%,0.74%,0.74%, Respectively. In the former group, the rate of drug resistance to eight anti-tuberculosis medications including INH, SM, FPR, EB, OFX, CPM, K and AK was 17.86%,16.07%,3.57%,5.36%,3.57%,0%,0%,0%; in the latter group, the rate of resistance to eight anti-tuberculosis drug was 26.25%,8.75%,12.50%, 7.50%,2.50%,1.25%,1.25%. The resistant rates to 1,2,3 and 4 or more drugs were 17.86%,3.57%,5.36%and0% in new cases and 5.00%,13.75%,3.75% and 0% in previously treated cases, comparing patients from primary versus recurrent evaluated by X2 test, there was a statistically significant difference in the resistant rates to 2. The total drug resistant rate did not show significant difference (P>0.05) among different age groups; The initial drug resistant rate did not show significant difference (P>0.05) among different sex and age groups. Single non-conditional logistic regression analysis showed that The differences of gender、culture level、live address、occupation、chronic disease、cavity、the history of previous treatment、delaye were not significantly correlated with drug resistance(P>0.05). Conclusion:To study, The rate of man-Mycobacterium tuberculosis was higher than that to other Bacteriums. The incidence of TB drug resistance is high and merit s at tention in the city of KaShi in Xin Jiang province. The problem of drug resistance was noted in 8 anti-tuberculosis medications to various degrees.This study demonstrated that the top three highly-resisted drug were isoniazid,streptomycin and rifampin.The initial drug resistant rate did not show influence among different sex and age groups. Routine Mycobacterium tuberculosis culture and drug susceptibility test were helpful in selecting anti-tuberculosis drug in a scientific,reasonable and effective manner.such tests also had epidemiological significance for controlling spread of tuberculosis.
引文
[1]Guernsey BG,AlexanderMR.Tubereulosis:review of treatment failure,relapse and drug resisantce.Am J Hosp Pharm,1978,35:690-698.
    [2]Centers for Disease Control and Prevention. Emergence of Mycobacterium tuberculosis with extensive resistance to secondline drugs-worldwide,2000-2004.MMWR Morb Monal Wkly Rep.2006.55:301-305.
    [3]Centers for Disease Control and Prevention.Extensively drugresistant tuberculosis— United States,1993-2006.MMWR Morb Mortal Wkly Rep,2007,56:250-253.
    [4]Global tuberculosis control:surveillance, planning, financing:WHO report 2008. "WHO/HTM/TB/2008.393"
    [5]全国结核病流行病学抽样调查技术指导组.2000年全国结核病流行病学抽样调查报告[J].中国防捞杂志,20002,24:65-108.
    [6]World Health Organization,Global tuberculosiscontrol epidemiology, strategy, finacing [R], WHO Report 2009, WHO/HTM/TB/2009.411.
    [7]World Health Organization,Global tuberculosis control and patient care:a ministerial meeting of high M/XDR-TB burden countries[R].Beijing,china,1-3 April,2009.
    [8]World Health organization.The Global MDR-TB & XDR-TB Response Plan (2007-2008).Geneva:WHO,2007:6.
    [9]玛依夏提·马合木提,刘来新,马建新,等.新疆卫V项目结核病人登记治疗管理分析.地方病通报,2004,19(2):73-74.
    [10]金鑫.1979-2000年新疆结核病流行状况及防治对策[J].地方病通报,2003,18(1):50-52.
    [11]曹红艳,吴长东,米利古,等.结核分枝杆菌新疆临床分离株耐药情况调查[J].中国病原生物学杂志,2010,5(4):253-255.
    [12]Rajendra Basnet, Sven Gudmund Hinderaker, Don Enarson,et al. Delay in the diagnosis of tuberculosis in Nepal [J]. BMC Public Health,2009,9:236.
    [13]杨本付,徐庵,蒋伟利,等.苏北农村耐药结核病现状及影响因素的研究[J].中华流行病学杂志,2004,25(7):582-585.
    [14]中国防痨协会.结核病诊断细菌学检验规程[J].中国防痨杂志,1996,18(1):28-31;1996,18(2):80-85;1996,18(3):127-134.
    [15]World Health Organization. Policy guidance on drug-susceptibility testing (DST) of second-line anti-tuberculosis drugs. Geneva.WHO/HTM/TB/2008.392.
    [16]中华医学会结核病学分会.肺结核诊断和治疗指南[J].中华结核和呼吸杂志,2001,24:70-74.
    [17]World Health Organization. Guidelines for the programmatic management of drug-resistant tuberculosis:emergency update 2008 [C]. Geneva:World Health Organization,2008.
    [18]Gisselbrecht M.Tuberculosis in elderly persons living in institutions.Rev Mai Respir,2004,21:106-113.
    [19]Stead WW,Dutt AK.Tuberculosis in the elderly.Semin Respir Infect,1989,4:189-197.
    [20]Ohmori M, Wada M, Yoshiyama T, et al. Factors related to early case detection of tuberculosis in health service facilities for the elderly. Kekkaku,2003,78:435-442.
    [21]中华人民共和国卫生部1990全国结核病流行病学抽样调查资料汇编[M].北京:人民卫生出版社,1990.8.
    [22]卢德友.1784例老年人肺结核临床特点分析[J].中华老年医学杂志.2005,24(7):530-531.
    [23]李亮,唐俊舫,端木宏谨,等.我国老年结核病流行现状分析[J].中华医学杂志,2006,86(37):2646-2648.
    [24]张翔.社会经济因素和结核病控制策略对结核病疫情的影响[J].现代预防医学,2007,34(5):889-890.
    [25]刘丽萍.农村基层卫生人员与村民结核病知识知晓率调查[J].中国防痨杂志,2008,30(1):65-66.
    [26]杨桦,曹金风,王海兵,等.182例分枝杆菌菌型鉴定和耐药性试验的研究[J].临床肺科杂志,2007,12(12):1047.
    [27]孙艳.结核分支杆菌耐药状况的研究[D].中国优秀学位论文,2007,1-37.
    [28]郭明星,张汉协,陈建军,等.猪源性牛型结核分支杆菌分离与鉴定[J].中国人兽共患病杂志.2005,21(10):920-922.
    [29]刘宇红,姜广路,赵立平,等.第四次全国结核病流行病学抽样调查-结核分支杆菌耐药性分析与评价[J].中华结核和呼吸杂志,2002,25(4):224-227.
    [30]Anti-tuberculosis drug resistance in the world. Fourth global report. The WHO/ IUATLD global project on anti-tuberculosis drug resistance surveillance,2002 2007[C]. Geneva:World Health Organization,2008.
    [31]World Health Organization.Anti-tuberculosis drug resistance in the world(fourth global report).The WHO/IUATLD global project on anti-tuberculosis drug resistence surveillance,2002-2007.Geneva:WHO,2008.
    [32]徐德顺,张思潮,杨俊超,等.浙江省湖州市区结核病耐药趋势分析[J].中国防痨杂志,2006,28(6):103-105.
    [33]许丽,杨应周,吴清芳,等.深圳市结核病一线抗结核药的耐药监测结果分析[J].中国防痨杂志,2010,32(4):204-207.
    [34]车洋,于梅,平国华,等.宁波地区1149株结核分枝杆菌耐药情况分析[J].中国卫生检验杂志,2010,20(6):1494-1495.
    [35]罗槑,叶飞,罗涛,等.成都市结核分枝杆菌耐药状况分析[J].华西医学2010,25(10):1854-1856.
    [36]卫生部疾病控制司,卫生部医政司,编.全国结核病防治工作手册[M].北京:卫生部,1999.52-62.
    [37]World Health organization Global tuberculosis control:epidemiology, strategy, financing[R]. WHO Report 2009, WHO/HTM/TB/2009.41.
    [38]Yu MC,Wu MH,Jou R.Extensively drug-resistant tuberculosis,Taiwan[J].Emerg Infect Dis,2008,14(5):849-850.
    [39]Zhao M,Li X,Xu P,Shen X,Gui X,Wang L,Deriemer K,Mei J,Gao Q.Transmission of MDR and XDR tuberculosis in Shanghai,China[J].PLoS ONE,2009,4(2):4370.
    [40]Sun Z,Chao Y,Zhang X,et al.Characterization of Extensively Drug-Resistant Mycobacterrium tuberculosis Clinical Isolates in China[J]. J Clin Microbiol, 2008,46(12):4075-4077.
    [41]包洪,于庭,印璞,等.中国部分地区结核分支杆菌耐利福平、异烟肼和链酶素耐药基因的检测[J].中国实验诊断学,2007,11(2):232-234.
    [42]陆阳,吴雪琼,张俊仙,等.膜反向斑点杂交技术检测结核分枝杆菌耐乙胺丁醇基因型[J].中国现代医学杂志,2007,17(6):658—661.
    [43]杨松.结核病耐药的分子机制及其防治研究进展[J].临床肺科杂志,2006,11(5):632—633.
    [44]胡忠义.噬菌体生物扩增法检测结核分枝杆菌及其耐药性方法评价[J].中华检验医学杂志2007,30:821-823.
    [45]许丽,杨应周,吴清芳,等.深圳市结核病一线抗结核药的耐药监测结果分析[J].中国防痨杂志,2010,32(4):204-207.
    [46]Yamada N,Saorith K, Yamakami K. The national tuberculosis drug resistance survey in Cambodia,2000-2001 [J]. Int J Tuberc Lung Dis,2007,11 (12):1321-1327.
    [47]Marra F,Marra CA,Moadebi S,et al. Levofloxacin treatment of active tuberculosis and the risk of adverse events.Chest,2005,128(3):1406-1413.
    [48]唐神结,范琳,肖和平,等.印度孟买的结核分支杆菌对氟喹诺酮类药物耐药率上升[J].中华结核和呼吸杂志,2009,32(8):612.
    [49]中国防痨协会,耐药结核病化学治疗指南(2009)[J].2010,32(4):181-198.
    [50]成玉妹,曾晓蓉,吴艳红.泉州市2001-2005年肺结核病人结核分枝杆菌耐药性状况分析[J].中国防痨杂志,2009,31(2):68-70.
    [51]唐神结,肖和平,夏祥新等.不同年龄组结核分枝杆菌耐药性的研究[J].中华结核和呼吸杂志,2001,24(2):83.
    [52]孙道芳,陈延芳.156例住院肺结核患者结核杆菌耐药情况分析[J].2010,32(8):470-471.
    [53]石荔,魏淑贞.西藏地区217株结核分枝杆菌的药物敏感性检测分析[J].中华医院感染学杂志,2009,19(18):2476-2477.
    [54]唐神结,肖和平,胡忠义,等.耐药结核病防治手册[M].人民卫生出版社,2009:6.
    [55]唐神结,肖和平,夏祥新等.不同年龄组结核分枝杆菌耐药性的研究[J].中华结核和呼吸杂志,2001,24(2):8.
    [56]杨本付,徐庵,蒋伟利,等.苏北农村耐药结核病现状及影响因素的研究[J].中华流行病学杂志,2004,25(7):582-585.
    [57]张弘,张爱洁,赵平,等.北京市朝阳区肺结核患者耐药状况及相关因素分析[J].中国防痨杂志,2009,(31):218-222.
    [58]张拓红,玛依夏提,范新春,等.贫困地区医患互动与肺结核患者的发现和治疗[J].中华医院管理杂志,2005,21(7):481-483.
    [59]周开元,李璐,李军梅,等.雾化吸入抗痨药对耐药肺结核的疗效观察[J].临床肺科杂志,2005.10(2):137-140.
    [60]胡忠义.结核病免疫学诊断技术研究进展[J].中国防痨杂志,2005,27:6-8.
    [61]聂理会,初乃惠.肺结核的综合治疗[J].中国临床医生,2009,37(7):486-488.
    [62]张广莉,陶曙,张凤玲,等.提高耐药肺结核病患者依从性的探讨[J].广州医药,2006,37(6):60-62.
    [1]Scheele S,Dolin P. Consensus statementl Global burden of tuberculosis:estimated incidence, prevalence,and mortality by country WHO Global Surveillance and Monitoring Project. JAMA,1999,282:677-686.
    [2]刘宇红,姜广路,赵立平,等.第四次全国结核病流行病学抽样调查-结核分枝杆菌耐药性分析与评价.中华结核和呼吸杂志,2002,25:224-227.
    [3]Wolrld Health organization.The Global MDR-TB & XDR-TB Response Plan (2007-2008). Geneva:WHO,2007:6.
    [4]孙冰梅,车志宏.结核分枝杆菌耐药的分子机制及耐药基因检测方法的研究进展.山西医药杂志,2005,4(4):301-303.
    [5]Oliveira JS,Pereira JH,Cardmi F,et al. Crstallographic and presteady. state kinetics studies on binding Of NADH to wild-type and isoniazid-resistant enoyl-ACP(CoA)Reduetase enzymes from Mycobacteritum tuberculosis.Mol Bio,2006,359(3):646-666.
    [6]华正豪.结核分枝杆菌耐异烟肼的分子机制.国外医学,2002,25(5):31-33.
    [7]Zhang Y,Allen B.The catalase-peroxidase gene and isoniazid resistance of Mycobacteritum tuberculosis.Nature,1992,358:591-593.
    [8]Brien KL,Dietz HC,Romagnoli M, et al.Evaluation of inhA gene and catalase-peroxidase gene among isoniazid-sensitive and resistant Mycobacterium tuberculosis isolates.Mol Cell Probes,1996,10:126.
    [9]Leung ET,Ho PL,Yuen KY,et al.Molecular Characterization of isoniazid resistance in Mycobacteritum Tuberculosis:identificating of a novel mutation in inhA.antimicrob ngents Chemother,2006,50:1075-1078.
    [10]Heym B,Stavropoulos E,Honore N,et al.Effects of overepression of the alkyl hydroperxide reductase Ahpc on the virulence and isoniazid resistance of Mycobacteritum Tuberculosis.Infect Immum,1997,65:1395-1401.
    [11]朱中元,陈贻平,王海波,等.耐多药结核分枝杆菌基因变异研究.中华检验医学杂志,2000,23:26-28.
    [12]Huitric E,Wemgren J,Jureen,et al.Resistance levels and rpoB gene mutations among in vitro-selected rifampin-resistant Mycobacteritum tuberculosis mutant.Antimicrob Agents chemether,2006,50(8):2860-2862.
    [13]Rat tan A,Kalia A,A hmad N,et al. Multidrug resistant mycobacterium tuberculosis molecular perspect ives. Emerg Infect D is,1998,4 (2):195-209.
    [14]Isakova ZHT, Pak OA, Iusupova E, et al. Use of biologicalm icrochips in the determ-ination of drugresistance of mycobacterium tuberculosis torifampicin. Probl Tuberk Bolezn Legk,2005, (8):50-53.
    [15]Ramaswamy S,Amin AG,Goksel S,et al.Molecular genetic analysis of nucleotide poly-morphisms associated with ethambutol resistance in humanisolates of Myco-bacterium Tuberculosis.Antimicrob Anents Chemother,2000,44(2):32.
    [16]Rinder H, Mieskes KT, Tortoli E, et al. Detection of embB codon 306 mutations in etham butol resistant Mycobacterium tuberculosis directly form sputum samp les:a low-cost, rapid appraoch. Modecular and Cellular Probes,2001,15:37-42.
    [17]Wu XQ,Liang JQ,Zhang JX,et al.Deteation and evaluation of the mutations of embB Gene in ethambutol-susceptible and vesistant Mycobacteritum tuberculosis isolates from china.chin Med(Engl),2005,118:1739-1741.
    [18]Dobner P,Bretzel G, Rusch-Gerdes S, et al. Geographic variation of the predictive values of genomic mutations associated with strep tomycin resistance in Mycobacterium tuberculosis. Mol Cell Probes,1997,11:123-126.
    [19]Honore N,Cole ST.Streptomycin resistence in mycobacteria Antimicrob Agents chemother 1994,38:238-242.
    [20]Douglass J, Steyn. LM1 A ribosomal gene mutation in streptomycin-resistant Myco-bacterium tuberculosis isolates. Infect Dis,1993,167:1505-1506.
    [21]Okamoto S,Tamaru A,Nakajima C,et al.Loss of a conserved 7-methylguanosine modify-cation in 16s rRNA confers lowlevel streptomycin resistance in bacteria Mol Microbiol, J Biol Chem,2007,63:1096-1106.
    [22]Scorpio A,Zhang Y.Mutations in pncA,a gene encoding pyrazinamidase,cause resistance to the antitubeiculous drug pxrazinamide in tubercie bacillus.Nat Me, 1996,2:662-667.
    [23]Cheng sJ,Thibert L,Smlehez T,et al.pncA mutations as a major mechanism of pyrazinamde resistence in Mycobacteritum tuberculosis spread of a monoresistant strain in Quebec,Canada.Antimicrob Agents chemother,2000,44(3):528-532.
    [24]Yu S,Girotto S,Lee C,et al.Reduced affinity for ioniazid in the S315T mutant of Mycobacterium tuberculosis katG is a key factor in antibiotic resistance.J Biol Chem,2003,278 (17) 14769-14775.
    [25]Aubry A, Veziris N, Cambau E, et al. Novel gyrase mutations in quinolone-resistant and hypersusceptible clinical isolates of Mycobacterium tuberculosis:functional analysis of mutant enzymes.Antimicrob Agents Chemother,2006,50:104-112.
    [26]Giannoni F, Iona E, Sementilli F, et al. Evaluation of a new line probe assay for rapid identification of gyrA mutations in Mycobacterium tuberculosis. Antimicrob Agents Chemother,2005,49:2928-2933.
    [27]Park IN,Hong SB,Oh YM,et al. Impact of short-term exposure to fluoroquinolones on otloxacin resistance in HIV-negative patients with tubereulesis. Int J Tubere drug Dis,2007,11(3):319-324.
    [28]Sulochana S,Narayanan S,Paramasivan CN,et al. Analysis of fluoroquinolone resistance in clinical isolates of Mycobacterium tuberculosis from India. J Chemother,2007,19(2):166-171.
    [29]Engohang-Ndong J,Baillat D,AumericierM, et al. EthR, a rep ressor of the TetR/ CamR family imp licated in ethionamide resistance in mycobacteria, octamerizes cooperatively in its operator. Mol Microbiol,2004,51 (1):175-188.
    [30]Maus CE, Plikaytis BB.,Shinnick TM. Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother,2005,49: 571-577.
    [31]Maus CE, Plikaytis BB, Shinnick TM. Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother,2005,49: 571-577.
    [32]Maus CE, Plikaytis BB, Shinnick TM. Molecular analysis of cross-resistance to cap-reomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis. Antimicrob Agents Chemother,2005,49:3192-3197.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700