福建省耐多药结核分枝杆菌对吡嗪酰胺耐药性的研究

doi:10.3969/j.issn.2095-3755.2018.02.010

摘要/Abstract

摘要：

目的分析福建省耐多药结核病(MDR-TB)患者临床分离菌株对吡嗪酰胺(PZA)的耐药情况,为MDR-TB的防治工作提供科学依据。方法收集2008—2010年福建省疾病预防控制中心在结核病耐药监测期间获得的119例MDR-TB患者的临床分离菌株及其患者基本信息,患者平均年龄(45.8±15.3)岁,男性占76.5%(91/119),流动人口占30.3%(36/119),农民占55.5%(66/119),小学及以下学历的患者占53.8%(64/119)。以标准株H37Rv作对照,采用BACTEC ^TM MGIT 960 ^TM系统(简称“MGIT 960”)和WHO推荐的比例法在固体L-J培养基上对菌株进行PZA及其他抗结核药物的敏感性试验(简称“药敏试验”)。采用SPSS 17.0软件对数据进行描述性分析,计数资料的比较采用χ ²检验,以P<0.05为差异有统计学意义。结果 119株临床分离的耐多药菌株对PZA的耐药率达37.0%(44/119)。不同人口学特征的MDR-TB患者间仅小学及以下学历者对PZA的耐药率(26.6%,17/64)低于小学以上学历者(49.1%,27/55)(χ ²=6.44,P=0.011);对乙胺丁醇、链霉素、氧氟沙星、左氧氟沙星、莫西沙星耐药的患者对PZA的耐药率分别为48.6%(36/74)、44.9%(31/69)、62.5%(20/32)、63.3%(19/30)、71.4%(10/14),明显高于对上述药物敏感者对PZA的耐药率[分别为17.8%(8/45)、26.0%(13/50)、27.6%(24/87)、28.1%(25/89)、32.4%(34/105)](χ ²=11.44,P=0.001;χ ²=4.46,P=0.035;χ ²=12.24,P<0.001;χ ²=11.96,P=0.001;χ ²=8.08,P=0.004)。结论在福建省MDR-TB防治工作中,需重视对吡嗪酰胺的药敏试验检测,及时给予患者更加有效的治疗方案。

关键词: 分枝杆菌, 结核, 结核, 抗多种药物性, 吡嗪酰胺, 数据说明, 统计, 福建省

Abstract:

Objective To analyze the pyrazinamide (PZA) resistance in multidrug-resistant Mycobacterium tuberculosis (MDR-TB) clinical isolates in Fujian province.Methods A total of 119 MDR-TB clinical isolates and the basic information of MDR-TB patients were collected during the antituberculosis drug resistance surveillance in Fujian Center for Disease Control and Prevention from 2008 to 2010. The average age of the patients was (45.8±15.3) years, of which 76.5% (91/119) were male, 30.3% (36/119) were floating population, 55.5% (66/119) were peasants, and 53.8% (64/119) were patients with primary school education or below. Using the standard strain H37Rv as the control, the BACTEC ^TM MGIT 960 ^TM system (MGIT 960) and the proportional method recommended by the WHO were used to perform the drug susceptibility test of PZA and other antituberculosis drugs on strains in the L-J solid medium. The descriptive analysis of data was performed by SPSS 17.0, and the Chi square test was used on enumeration data. P<0.05 was considered statistically significant. Results Of these 119 MDR-TB clinical isolates, 44 were detected resistant to PZA (37.0%). Among the MDR-TB patients with different demographic characteristics, the PZA resistance rate of patients with primary school education or below (26.6%, 17/64) was lower than those with above primary school education (49.1%, 27/55) (χ ²=6.44, P=0.011). The PZA resistance rates in patients with ethambutol, streptomycin, ofloxacin, levofloxacin and moxifloxacin resistance was 48.6% (36/74), 44.9% (31/69), 62.5% (20/32), 63.3% (19/30), and 71.4% (10/14), respectively; which was significantly higher than that of sensitive patients (17.8% (8/45), 26.0% (13/50), 27.6% (24/87), 28.1% (25/89), and 32.4% (34/105))(χ ²=11.44, P=0.001; χ ²=4.46, P=0.035; χ ²=12.24, P<0.001; χ ²=11.96, P=0.001; χ ²=8.08, P=0.004). Conclusion We should pay more attention to the PZA susceptibility test to provide timely and effective treatment to the patients in the prevention and treatment of multidrug-resistant tuberculosis in Fujian province.

Key words: Mycobacterium tuberculosis, Tuberculosis, multidrug-resistant, Pyrazinamide, Data interpretation, statistical, Fujian province

周银发,张山鹰,魏淑贞,林勇明,赵永,林建,林淑芳. 福建省耐多药结核分枝杆菌对吡嗪酰胺耐药性的研究[J]. 结核病与肺部健康杂志, 2018, 7(2): 123-127. doi: 10.3969/j.issn.2095-3755.2018.02.010

Yin-fa ZHOU,Shan-ying ZHANG,Shu-zhen WEI,Yong-ming LIN,Yong ZHAO,Jian LIN,Shu-fang. LIN. Analysis of pyrazinamide resistance in multidrug-resistant Mycobacterium tuberculosis in Fujian province[J]. Journal of Tuberculosis and Lung Health, 2018, 7(2): 123-127. doi: 10.3969/j.issn.2095-3755.2018.02.010

图/表 2

表1

表2

参考文献 23

[1]	World Health Organization . Global tuberculosis report 2017. Geneva:World Health Organization, 2017: 45-48.
[2]	徐彩红, 李仁忠, 陈明亭 , 等. 12省项目地区1157例耐多药结核病患者治疗情况分析. 现代预防医学, 2012,39(15):3944-3945.
[3]	Cui Z, Wang J, Lu J , et al. Evaluation of methods for testing the susceptibility of clinical Mycobacterium tuberculosis isolates to pyrazinamide. J Clin Microbiol, 2013,51(5):1374-1380. doi: 10.1128/JCM.03197-12 URL
[4]	肖和平, 屠德华, 朱莉贞 , 等. 耐药结核病化学治疗指南( 2015). 北京: 人民卫生出版社, 2015: 30-41.
[5]	肖东楼, 马玙, 朱莉贞 , 等. 抗结核药品不良反应诊疗手册 . 北京: 人民卫生出版社, 2015: 41-47.
[6]	中华人民共和国卫生部. 全国结核病耐药基线调查报告.北京: 人民卫生出版社, 2010: 129-133.
[7]	中国防痨协会基础专业委员会. 结核病诊断实验室检验规程.北京: 中国教育文化出版社, 2006.
[8]	World Health Organization . Guidelines for surveillance of drug resistance in tuberculosis. Geneva:Switzerland WHO Global Tuberculosis Program, 2003.
[9]	Demers AM, Venter A, Friedrich SO , et al. Direct Susceptibility Testing of Mycobacterium tuberculosis for Pyrazinamide by Use of the Bactec MGIT 960 System. J Clin Microbiol, 2016,54(5):1276-1281.
[10]	刘伟, 孙峰, 张文宏 , 等. 基于吡嗪酰胺药物敏感性改善耐多药结核病治疗结局的研究进展. 结核病与肺部健康杂志, 2014,3(2):77-81.
[11]	彭红侠, 张小艳 . 吡嗪酰胺治疗耐多药肺结核的临床效果观察. 西南国防医药, 2016,26(5):497-499.
[12]	周银发, 林淑芳, 成玉妹 , 等. 惠安县涂阳肺结核患者治疗转归特征及影响因素分析. 海峡预防医学杂志, 2016,22(6):27-29.
[13]	戴志松, 杜永成, 柳珍妮 , 等. 2004—2013年福建省肺结核流行特征分析. 预防医学论坛, 2016,22(8):574-577,581.
[14]	周银发, 张山鹰, 柳珍妮 , 等. 242例耐多药结核病患者特征及治疗转归的影响因素分析. 中国防痨杂志, 2017,39(11):1218-1222.
[15]	夏辉, 郑扬, 赵雁林 . 我国耐多药结核分枝杆菌对吡嗪酰胺和莫西沙星的耐药性研究. 中国预防医学杂志, 2015,16(4):241-244.
[16]	Gu Y, Yu X, Jiang G , et al. Pyrazinamide resistance among multidrug-resistant tuberculosis clinical isolates in a national referral center of China and its correlations with pncA, rpsA, and panD gene mutations. Diagn Microbiol Infect Dis, 2016,84(3):207-211.
[17]	饶运帷 . 吡嗪酰胺耐药对肺结核疗效的影响研究. 广州:广州医科大学, 2014: 19-22.
[18]	Mansjo M, Werngren J, Hoffner S . Characterization of pyrazi-namide resistance in consecutivemultidrug-resistant Mycobacterium tuberculosis isolates in sweden between 2003 and 2015. Int J Mycobacteriol, 2017,6(2):156-161.
[19]	任丽娟, 黄正谷, 王丽 , 等. 耐多药结核分枝杆菌对氟喹诺酮类药物体外交叉耐药及耐药性研究. 中国药房, 2015,26(11):1488-1490.
[20]	宋艳华, 高孟秋, 李琦 , 等. 结核分枝杆菌rpsL和rrs基因突变与氨基糖苷类和多肽类抗结核药物耐药的关系. 中国防痨杂志, 2016,38(10):799-804.
[21]	陈明亭, 李仁忠, 阮云洲 , 等. 耐多药结核病防治标准化培训教程.北京: 人民卫生出版社, 2015: 41-47.
[22]	Chang KC, Leung CC, Yew WW , et al. Pyrazinamide may improve floroquinolone-based treatment of multidrug-resistant tuberculosis. Antimicrob Agents Chemother, 2012,56(11):5465-5475.
[23]	Ngabonziza JCS, Diallo AB, Tagliani E , et al. Half of rifam-picin-resistant Mycobacterium tuberculosis complex isolated from tuberculosis patients in Sub-Saharan Africa have concomitant resistance to pyrazinamide. PLoS One, 2017,12(10):e0187211.

人口学特征	例数	对PZA的耐药情况		χ²值	P值
人口学特征	例数	敏感[例(株) (构成比,%)]	耐药[例(株) (构成比,%)]	χ²值	P值
性别				0.08	0.772
男	91	58(63.7)	33(36.3)
女	28	17(60.7)	11(39.3)
年龄(岁)				0.39	0.824
<35	33	21(63.6)	12(36.4)
35~	65	42(64.6)	23(35.4)
≥60	21	12(57.1)	9(42.9)
户籍				0.08	0.776
常住	83	53(63.9)	30(36.1)
流动	36	22(61.1)	14(38.9)
学历				6.44	0.011
小学及以下	55	28(50.9)	27(49.1)
小学以上	64	47(73.4)	17(26.6)
职业				0.04	0.982
农民	66	42(63.6)	24(36.4)
企事业	48	30(62.5)	18(37.5)
下岗及待业	5	3(60.0)	2(40.0)
抗结核治疗史				0.10	0.757
有	59	38(64.4)	21(35.6)
无	60	37(61.7)	23(38.3)

药物药敏试验结果	PZA		χ²值	P值
药物药敏试验结果	敏感[例(株) (构成比,%)]	耐药[例(株) (构成比,%)]	χ²值	P值
E			11.44	0.001
敏感	37(82.2)	8(17.8)
耐药	38(51.4)	36(48.6)
Sm			4.46	0.035
敏感	37(74.0)	13(26.0)
耐药	38(55.1)	31(44.9)
Ofx			12.24	<0.001
敏感	63(72.4)	24(27.6)
耐药	12(37.5)	20(62.5)
Lfx			11.96	0.001
敏感	64(71.9)	25(28.1)
耐药	11(36.7)	19(63.3)
Mfx			8.08	0.004
敏感	71(67.6)	34(32.4)
耐药	4(28.6)	10(71.4)
Km			0.24	0.623
敏感	66(62.3)	40(37.7)
耐药	9(69.2)	4(30.8)
Am			0.00	0.975
敏感	70(63.1)	41(36.9)
耐药	5(62.5)	3(37.5)
Cm			0.06	0.814
敏感	69(62.7)	41(37.3)
耐药	6(66.7)	3(33.3)
PAS			0.24	0.627
敏感	67(63.8)	38(36.2)
耐药	8(57.1)	6(42.9)
Pto			0.15	0.700
敏感	74(63.2)	43(36.8)
耐药	1(50.0)	1(50.0)