重庆市肺结核患者异烟肼与丙硫异烟胺耐药状况分析
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摘要
目的了解重庆市结核分枝杆菌异烟肼(INH)、丙硫异烟胺(Pto)及其交叉耐药情况,为重庆市耐药结核病的防控提供参考。方法根据重庆市2015-2017年39个区县培养阳性菌株的传统药敏试验结果,收集288例INH或Pto任意耐药菌株,分析其耐药情况。结果 288例菌株中,INH耐药菌株285例,Pto耐药菌株19例,交叉耐药菌株16例。复治患者INH或Pto的耐药率均高于初治患者,年龄15～44岁患者Pto耐药率显著高于INH组。Pto耐药组Pre-XDR-TB及Ofx耐药率显著高于INH组。交叉耐药菌株中,年龄15～44岁组交叉耐药率较高,且MDR-TB发生率高达93.8%。结论重庆市INH与Pto耐药情况已较为严重,医生在为INH耐药患者制定化疗方案时应根据药敏结果,应谨慎选择Pto进行替代治疗,以避免更多耐药的发生。
In this study, we investigated the drug-resistant characteristics of isoniazid(INH)-resistant strains, protionamide(Pto)-resistant strains and their cross-resistant strains in tuberculosis patients, to provide evidences for the prevention and control of drug-resistant patients in Chongqing. According to the result of drug susceptibility test, 288 strains that any-drug resistant to INH and Pto were collected and analyzed for their drug-resistant characteristics. Among the 288 any-drug resistant strains, 285 strains were INH-resistance, 19 strains were Pto resistance and 16 strains were cross-resistance to INH and Pto. Drug resistant rate of INH or Pto in retreatment patients was higher than in initial patients;patients from 15 to 44 years old group have much higher Pto resistant rate than INH resistant rate(P<0.05). Pre-XDR rate and ofloxacin resistant rate in Pto resistant group were much higher than in INH resistant group(P<0.05). In INH and Pto cross-resistant strains, the cross-resistant rate was higher in the patients from 15 to 44 years old group compared to other groups, there was no INH and Pto cross-resistant patients in more than 60 years old group; the MDR rate in cross-resistant strains was up to 93.8% and the XDR-TB rate was up to 43.8%. For the regional distribution, 56.2% INH and Pto cross-resistant patients was in Wanzhou District. For the 16 INH and Pto cross-resistant strains, there were nine kinds of drug resistant types and one patient was drug-resistance to all the ten kinds of drugs. Drug resistance for INH or Pto is serious in Chongqing. The regimen for INH-resistant patients should be according to the drug susceptibility result and choose Pto as a replacement carefully, to avoid further drug resistance.
In this study, we investigated the drug-resistant characteristics of isoniazid(INH)-resistant strains, protionamide(Pto)-resistant strains and their cross-resistant strains in tuberculosis patients, to provide evidences for the prevention and control of drug-resistant patients in Chongqing. According to the result of drug susceptibility test, 288 strains that any-drug resistant to INH and Pto were collected and analyzed for their drug-resistant characteristics. Among the 288 any-drug resistant strains, 285 strains were INH-resistance, 19 strains were Pto resistance and 16 strains were cross-resistance to INH and Pto. Drug resistant rate of INH or Pto in retreatment patients was higher than in initial patients;patients from 15 to 44 years old group have much higher Pto resistant rate than INH resistant rate(P<0.05). Pre-XDR rate and ofloxacin resistant rate in Pto resistant group were much higher than in INH resistant group(P<0.05). In INH and Pto cross-resistant strains, the cross-resistant rate was higher in the patients from 15 to 44 years old group compared to other groups, there was no INH and Pto cross-resistant patients in more than 60 years old group; the MDR rate in cross-resistant strains was up to 93.8% and the XDR-TB rate was up to 43.8%. For the regional distribution, 56.2% INH and Pto cross-resistant patients was in Wanzhou District. For the 16 INH and Pto cross-resistant strains, there were nine kinds of drug resistant types and one patient was drug-resistance to all the ten kinds of drugs. Drug resistance for INH or Pto is serious in Chongqing. The regimen for INH-resistant patients should be according to the drug susceptibility result and choose Pto as a replacement carefully, to avoid further drug resistance.
引文
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[16] Alame-Emane AK, Xu P, Pierre-AudigierC,et al. Pyrazinamide resistance in Mycobacterium tuberculosis arises after rifampicin and fluoroquinoloneresistance[J]. Int J Tuberc Lung Dis,2015, 19(6):679-684. DOI:10.5588/ijtld.14.0768
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[18] Zhang Z, Lu J, Wang Y,et al. Prevalence and molecular characterization of fluoroquinolone-resistant Mycobacterium tuberculosis isolates in China[J].Antimicrob Agents Chemother,2014,58(1):364-369. DOI:10.1128/AAC.01228-13
[19] 陈曦,马玙,金奇,等.耐异烟肼结核分枝杆菌临床分离株耐药相关基因突变研究[J].中华结核和呼吸杂志,2005,28(4):250-253.
[2] 肖和平.耐药结核病化学治疗指南(2015)[M]. 北京:人民卫生出版社,2015,7-8.
[3] 王燕森,管茶香,万康林,等.异烟肼耐药结核病与耐多药结核病的影响因素研究[J]. 中国预防医学杂志,2015,16(10):792-795. DOI:10.16506/j.1009-6639.2015.10.014
[4] 赵雁林,逄宇.结核病实验室检验规程[M].北京:人民卫生出版社,2015.
[5] 胡彦,刘洁,刘英,等.重庆市耐多药结核病患者广泛耐药及广泛耐药前期发生情况分析[J].中国防痨杂志,2016,38(9):727-731. DOI:10.3969/j.issn.1000-6621.2016.09.007
[6] 李心德.174株耐多药结核分枝杆菌对二线抗结核药耐药情况分析[J].国际检验医学杂志,2014,35(13):1732-1733,1748. DOI: 10.3969/j.issn.1673-4130.2014.13.028
[7] 刘银萍,王杰,张俊仙,等.对异烟肼与丙硫异烟胺耐药的结核分枝杆菌临床分离株检测及相关基因突变的研究[J].中国防痨杂志,2016,38(9):718-721. DOI:10.3969/j.issn.1000-6621.2016.09.005
[8] Tan YJ, Su BY, Zheng HW, et al. Molecular haracterization of prothionamide-resistant Mycobacterium Tuberculosisisolates in Southern China[J].Front Microbiol, 2017,8:2358. DOI: 10.3389/fmicb.2017.02358
[9] 汪清雅,胡代玉,刘英,等.重庆市主城区肺结核耐药情况分析[J].重庆医学,2014,43(22):2913-2915. DOI:10.3969/j.issn.1671-8348.2014.22.029
[10] Merza MA, Famia P, Tabarsi P, et al.Anti-tuberculosis drug resistance and associated risk factors in a tertiary level TB centre in Iran: a retrospective analysis[J]. J Infect Dev Ctries, 2011, 5(7):511-519. DOI:10.3855/jidc.1259
[11] World Health Organization.Multidrug and extensively drug-resistant TB(M/XDR-TB):2010 global report on surveillance and response[R]. Geneva: World Health Organization,2010.
[12] 李雨晴, 万李, 陈杏, 等. 中国西北四省(区)结核分枝杆菌分离株一线药物耐药状况及其影响因素分析[J]. 中国人兽共患病学报, 2017, 33(5), 398-402, 422. DOI:10.3969/j.issn.1002-2694.2017.05.003
[13] 杨安文, 周亮, 徐祖辉, 等. 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[J]. 中国人兽共患病学报, 2018, 34(5): 396- 403. DOI:10.3969/j.issn.1002-2694.2018.00.074
[14] Mishal SK, Wu SS, Wu W, et al. Optimising routine surveillance systems for informing tuberculosis control policies in China[J]. Health Policy and Planning,2017,32, suppl.2, ii12- ii14. DOI:10.1093/heapol/czx051
[15] 高谦,梅建.传播才是造成我国结核病高耐药率的主要原因[J].中国防痨杂志,2015,37(11):1091-1096. DOI:10.3969/j.issn.1000-6621.2015.11.002
[16] Alame-Emane AK, Xu P, Pierre-AudigierC,et al. Pyrazinamide resistance in Mycobacterium tuberculosis arises after rifampicin and fluoroquinoloneresistance[J]. Int J Tuberc Lung Dis,2015, 19(6):679-684. DOI:10.5588/ijtld.14.0768
[17] Baharoglu Z, Mazel D. Vibrio cholerae triggers SOS and mutagenesis in response to a wide range of antibiotics: a rout towards multiresistance[J].Antimicrob Agents Chemother. 2011,55(5):2438-2441. DOI: 10.1128/AAC.01549-10
[18] Zhang Z, Lu J, Wang Y,et al. Prevalence and molecular characterization of fluoroquinolone-resistant Mycobacterium tuberculosis isolates in China[J].Antimicrob Agents Chemother,2014,58(1):364-369. DOI:10.1128/AAC.01228-13
[19] 陈曦,马玙,金奇,等.耐异烟肼结核分枝杆菌临床分离株耐药相关基因突变研究[J].中华结核和呼吸杂志,2005,28(4):250-253.