263例结核病并发HIV感染成年患者MTB耐药及耐药基因突变检测结果分析

doi:10.3969/j.issn.2096-8493.2020.01.012

摘要/Abstract

摘要：

目的了解263例结核病并发HIV感染患者的MTB耐药率、耐药谱及耐药基因的分布,为临床治疗提供指导和帮助。方法收集2017年7月1日至2019年6月30日于成都市公共卫生临床医疗中心确诊为结核病并发HIV感染、符合纳入与排除标准的263例患者作为研究对象。采用BACTEC MGIT 960鉴定系统进行菌种鉴定,微孔板比例法进行药物敏感性试验(简称“药敏试验”),DNA微阵列芯片法检测耐药基因。对患者的耐药率、耐药谱及耐药基因分布等方面进行分析。结果 263例结核病并发HIV感染患者,共计78例发生MTB耐药,总体耐药率为29.7%,耐药顺位依次如下:INH(14.8%,39/263)、RFP(11.0%, 29/263)、Sm(8.4%,22/263)、Mfx(6.5%, 17/263)、Rfb(6.1%,16/263)、Lfx(4.6%,12/263)、EMB(4.2%,11/263)、Pto(3.4%, 9/263)、PAS(3.0%,8/263)。复治结核病并发HIV感染者耐药率为57.4%(35/61),明显高于初治结核病并发HIV感染者[21.3%(43/202)],差异有统计学意义(χ²=29.25,P=0.000)。对INH耐药的耐药基因突变顺位依次为katG 24株(68.6%,24/35)、inhA 11株(31.4%,11/35);对RFP耐药的耐药基因突变位点顺位依次为rpoB 531位点16株(61.5%,16/26),rpoB 526位点7株(26.9%,7/26),rpoB 516位点3株(11.5%,3/26)。结论结核病并发HIV感染患者耐药率较高,以耐一线抗结核药品为主,对RFP耐药以rpoB 531位点突变最为常见,对INH耐药以katG基因突变常见。

关键词: 结核,肺, HIV感染, 共病现象, 结核,抗多种药物性, 基因型, 突变, 研究报告

Abstract:

Objective To investigate the MTB resistance rate, resistance spectrum and distribution of resistance genes in tuberculosis and HIV co-infection patients to provide guidance for clinical treatment. Methods A total of 263 patients with tuberculosis and HIV co-infection who met the inclusion and exclusion criteria in Chengdu Public Health Clinical Center from July 1, 2017 to June 30, 2019 were collected as the research objects. BACTEC MGIT 960 identification system was used for bacterial type identification, microplate proportion method was used for drug sensitivity test, and DNA microarray chip was used to detect drug resistance genes. The drug resistance rate,spectrum and gene distribution were analyzed among these patients. Results Among the 263 tuberculosis patients complicated with HIV infection, a total of 78 cases developed MTB resistance, with an overall drug resistance rate of 29.7%. The distributions of anti-tuberculosis drug resistance were as follows:INH (14.8%, 39/263),RFP (11.0%, 29/263),Sm (8.4%, 22/263),Mfx (6.5%, 17/263),Rfb (6.1%, 16/263),Lfx (4.6%, 12/263),EMB (4.2%, 11/263),Pto (3.4%, 9/263),PAS (3.0%, 8/263). The incidence of drug resistance in retreatment tuberculosis complicated with HIV infection was 57.4% (35/61), which was significantly higher than that in initial treatment tuberculosis complicated with HIV infection (21.3%, 43/202), and the difference was statistically significant (χ²=29.25,P=0.000). The drug resistance gene mutation of INH in katG were 24 strains (68.6%, 24/35) and 11 strains in inhA (31.4%, 11/35); the drug resistance gene mutation of RFP in rpoB 531 were 16 strains (61.5%, 16/26), 7 strains (26.9%, 7/26) in rpoB 526, and 3 strains (11.5%, 3/26) in rpoB 516. Conclusion The drug resistance rate of tuberculosis and HIV co-infection patients was higher, and distribution of the anti-tuberculosis drugs were mainly the first-line drugs. The rpoB531 mutations are the most common in RFP resistance, and katG mutations are common in INH resistance.

Key words: Tuberculosis, pulmonary, HIV infections, Comorbidity, Tuberculosis, multidrug-resistant, Genotype, Mutation, Research report

傅小燕, 黄涛, 陈晴, 何畏, 黄晓秋, 吴桂辉. 263例结核病并发HIV感染成年患者MTB耐药及耐药基因突变检测结果分析[J]. 结核与肺部疾病杂志, 2020, 1(1): 55-59. doi: 10.3969/j.issn.2096-8493.2020.01.012

FU Xiao-yan, HUANG Tao, CHEN Qing, HE Wei, HUANG Xiao-qiu, WU Gui-hui. Analysis the distribution of MTB resistance and resistance gene mutation in 263 adult tuberculosis patients with human immunodeficiency virus co-infection[J]. Journal of Tuberculosis and Lung Disease, 2020, 1(1): 55-59. doi: 10.3969/j.issn.2096-8493.2020.01.012

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药品	初治患者(202例)			复治患者(61例)			合计(263例)			χ²值^a	P值
药品	耐药例数	耐药率(%)	95%CI(%)	耐药例数	耐药率(%)	95%CI(%)	耐药例数	耐药率(%)	95%CI(%)	χ²值^a	P值
INH	16	7.9	4.0~11.8	23	37.7	25.9~49.5	39	14.8	9.8~17.6	30.59	0.000
RFP	10	5.0	1.1~8.9	19	31.4	19.6~43.2	29	11.0	7.1~14.9	30.15	0.000
EMB	5	2.5	0.5~4.5	6	9.8	2.0~17.6	11	4.2	2.2~6.2	4.61	0.031
Sm	11	5.4	1.5~9.3	11	18.0	8.2~27.8	22	8.4	4.5~12.3	8.08	0.045
Rfb	6	3.0	1.0~5.0	10	16.4	6.6~26.2	16	6.1	4.1~8.1	12.47	0.004
Lfx	3	1.5	0.5~3.5	9	14.8	5.0~24.6	12	4.6	2.6~6.6	16.02	0.000
Mfx	6	3.0	1.0~5.0	11	18.0	8.2~27.8	17	6.5	2.6~10.4	15.18	0.000
Pto	4	2.0	0.1~3.9	5	8.2	2.1~13.9	9	3.4	1.4~5.4	10.90	0.001
PAS	3	1.5	0.5~3.5	5	8.2	2.1~13.9	8	3.0	1.0~5.0	5.06	0.025
合计	43	21.3	15.4~27.2	35	57.4	45.6~69.2	78	29.7	23.8~35.6	29.25	0.000