Analysis of drug resistance situation results and rifampicin resistance characteristics in pulmonary tuberculosis patients in Tianshui City from 2015 to 2022

doi:10.19982/j.issn.1000-6621.20230366

Abstract

Abstract:

Objective: Analyze the drug resistance situation and basic characteristics of rifampicin resistance in pulmonary tuberculosis (PTB) patients from 2015 to 2022 in Tianshui City, Gansu Province, to provide scientific basis for optimizing the health policy of drug-resistant tuberculosis. Methods: Adopting a retrospective analysis method, we collected information of tuberculosis registration, laboratory testing, drug resistance screening and drug resistant tuberculosis diagnosis in Tianshui City from 2015 to 2022 from “China Disease Prevention and Control Information System” subsystem “Tuberculosis Management Information System”, analyzed etiologically positive rate among patients, drug susceptibility test results and resistance diagnosis time, etc. Results: From 2015 to 2022, a total of 8458 registered PTB patients were detected in Tianshui City, excluding tuberculous pleurisy, there were 7895 cases of PTB, with an etiologically positive rate of 28.32% (2236/7895), rising from 11.33% (177/1562) in 2015 to 61.30% (236/385) in 2022, showing an upward trend ( $χ t r e n d 2$ =1014.480, P=0.000). Among 2360 patients with PTB who should be screened for drug resistance in Tianshui City, the drug resistance screening rate was 85.00% (2006/2360), which increased from 54.80% (97/177) in 2015 to 93.39% (240/257) in 2022, showing an upward trend( $χ t r e n d 2$ =397.292, P=0.000), and the detection rate of drug resistance in Tianshui City was 98.90% (1984/2006), and the rifampicin resistance rate was 15.73% (312/1984), which increased from 10.42% (10/96) in 2015 to 28.57% (62/217) in 2017 and then decreased to 11.34% (27/238) in 2022, showing a trend of firstly increasing and then decreasing( $χ t r e n d 2$ =27.248, P=0.000). Among the 312 patients with rifampicin resistance, there were more males (198 cases, 63.46%) than females (114 cases, 36.54%), relatively concentrated among 20-29 years old (85 cases, 27.24%) and 40-49 years old (66 cases, 21.15%) patients, mainly farmers (213 cases, 68.27%), and sputum smear results were mostly positive (215 cases, 68.91%). The proportion of elderly patients (60-83 years old) increased from 9.52% (2/21) in 2016 to 25.93% (7/27) in 2022, showing a clear upward trend ( $χ t r e n d 2$ =4.801, P=0.028). The sputum smear positive rate decreased from 100.00% (10/10) in 2015 to 59.26% (16/27) in 2022, showing a downward trend( $χ t r e n d 2$ =17.664, P=0.000). The top three drug resistance profiles were RFP+INH+EMB (26.92%, 84/312), RFP (26.28%, 82/312), and RFP+INH (23.40%, 73/312). The median (quartile) diagnosis time for drug-resistant patients had decreased year by year from 145 (91, 196) days in 2016 to 21 (12, 39) days in 2019. Conclusion: The etiologically positive rate and drug resistance screening rate of PTB patients in Tianshui City had been increasing year by year from 2015 to 2022, the detection rate of rifampicin resistance fluctuated greatly, the time for drug resistance diagnosis had been significantly shortened. It is suggested to increase efforts for screening rifampicin resistance in elderly PTB patients to reduce spread of drug-resistant tuberculosis.

Key words: Tuberculosis, pulmonary, Tuberculosis, resistant to multiple drugs, Health service research, Population monitoring, Tianshui City

CLC Number:

R521
R195

Li Jianghong, Lei Caiying, Yan Shuping, Liu Xiaolan, Yang Qi, Wang Reqin, Liu Fang, Yang Shumin. Analysis of drug resistance situation results and rifampicin resistance characteristics in pulmonary tuberculosis patients in Tianshui City from 2015 to 2022[J]. Chinese Journal of Antituberculosis, 2024, 46(3): 340-348. doi: 10.19982/j.issn.1000-6621.20230366

Figures/Tables 9

年份	耐药肺结核高危人群			耐药肺结核非高危人群^a			合计
年份	登记例数	筛查例数	筛查率 (%,95%CI)	登记例数	筛查例数	筛查率 (%,95%CI)	登记例数	筛查例数	筛查率 (%,95%CI)
2015	37	18	48.65(32.54~64.75)	140	79	56.43(48.21~64.64)	177	97	54.80(47.47~62.13)
2016	22	17	77.27(59.76~94.78)	163	70	42.94(35.35~50.54)	185	87	47.03(39.83~54.22)
2017	60	49	81.67(71.88~91.46)	263	170	64.64(58.86~70.42)	323	219	67.80(62.71~72.90)
2018	42	42	100.00	324	295	91.05(87.94~94.16)	366	337	92.08(89.31~94.84)
2019	49	49	100.00	346	327	94.51(92.11~96.91)	395	376	95.19(93.08~97.30)
2020	48	48	100.00	337	332	98.52(97.23~99.81)	385	380	98.70(97.57~99.83)
2021	25	25	100.00	247	245	99.19(98.07~100.31)	272	270	99.26(98.25~100.28)
2022	30	30	100.00	227	210	92.51(89.09~95.94)	257	240	93.39(90.35~96.42)
合计	313	278	88.82(85.33~92.31)	2047	1728	84.42(82.84~85.99)	2360	2006	85.00(83.56~86.44)
$χ 趋势 2$ 值			61.658			346.019			397.292
P值			0.000			0.000			0.000

年份	筛查例数	耐药肺结核		利福平耐药肺结核		耐多药肺结核
年份	筛查例数	例数	检出率(%,95%CI)	例数	检出率(%,95%CI)	例数	检出率(%,95%CI)
2015	97	96	98.97(94.08~99.97)	10	10.42(4.31~16.53)	10	10.42(4.31~16.53)
2016	87	86	98.85(94.67~99.97)	21	24.42(15.34~33.50)	21	24.42(15.34~33.50)
2017	219	217	99.09(97.15~99.92)	62	28.57(22.56~34.58)	53	24.42(18.71~30.14)
2018	337	334	99.11(97.72~99.88)	56	16.77(12.76~20.77)	39	11.68(8.23~15.12)
2019	376	369	98.14(96.57~99.56)	57	15.45(11.76~19.13)	32	8.67(5.80~11.54)
2020	380	376	98.95(97.61~99.82)	51	13.56(10.10~17.02)	25	6.65(4.13~9.17)
2021	270	268	99.26(97.69~99.91)	28	10.45(6.79~14.11)	9	3.36(1.20~5.52)
2022	240	238	99.17(97.40~99.90)	27	11.34(7.32~15.37)	12	5.04(2.26~7.82)
合计	2006	1984	98.90(98.46~99.63)	312	15.73(14.12~17.33)	195	9.83(8.52~11.14)
$χ 趋势 2$ 值			0.072		27.248		56.393
P值			0.788		0.000		0.000

特征	2015年	2016年	2017年	2018年	2019年	2020年	2021年	2022年	总计	$χ 趋势 2$ 值	P值
性别										0.117	0.733
男性	6(60.00)	15(71.43)	39(62.90)	35(62.50)	33(57.89)	32(62.75)	19(67.86)	19(70.37)	198(63.46)
女性	4(40.00)	6(28.57)	23(37.10)	21(37.50)	24(42.11)	19(37.25)	9(32.14)	8(29.63)	114(36.54)
年龄组(岁)										1.648	0.199
<20	1(10.00)	1(4.76)	4(6.45)	6(10.71)	7(12.28)	0(0.00)	3(10.71)	2(7.41)	24(7.69)	0.309	0.843
20~29	5(50.00)	3(14.29)	18(29.03)	14(25.00)	17(29.82)	15(29.41)	6(21.43)	7(25.93)	85(27.24)	0.128	0.721
30~39	0(0.00)	1(4.76)	12(19.36)	6(10.71)	12(21.05)	7(13.73)	7(25.00)	2(7.41)	47(15.06)	10.522	0.470
40~49	4(40.00)	11(52.38)	13(20.97)	10(17.86)	9(15.79)	12(23.53)	2(7.14)	5(18.52)	66(21.15)	6.669	0.010
50~59	0(0.00)	3(14.29)	5(8.06)	11(19.64)	6(10.53)	5(9.80)	4(14.29)	4(14.81)	38(12.18)	0.391	0.531
60~83	0(0.00)	2(9.52)	10(16.13)	9(16.07)	6(10.53)	12(23.53)	6(21.43)	7(25.93)	52(16.67)	4.801	0.028
职业										15.589	0.029
农民	7(70.00)	19(90.48)	42(67.74)	29(51.79)	38(66.67)	36(70.59)	19(67.86)	23(85.19)	213(68.27)
其他	3(30.00)	2(9.52)	20(32.26)	27(48.21)	19(33.33)	15(29.41)	9(32.14)	4(14.81)	99(31.73)
痰涂片										17.664	0.000
阳性	10(100.00)	21(100.00)	51(82.26)	38(67.86)	30(52.63)	31(60.78)	18(64.29)	16(59.26)	215(68.91)
阴性	0(0.00)	0(0.00)	11(17.74)	18(32.14)	27(47.37)	20(39.22)	10(35.71)	11(40.74)	97(31.09)

References 28

[1]	World Health Organization. Global tuberculosis report 2022. Geneva: World Health Organization, 2022.
[2]	王泊宁, 李涛, 陈伟. 耐药结核病经济负担研究进展. 中国防痨杂志, 2023, 45(6): 607-612. doi:10.19982/j.issn.1000-6621.20230018.
[3]	李晴, 司红艳, 马玲, 等. 2014—2017年甘肃省结核分枝杆菌耐药监测结果分析. 中国防痨杂志, 2021, 43(11): 1183-1193. doi:10.3969/j.issn.1000-6621.2021.11.014.
[4]	赵雁林, 逄宇. 结核病实验室检验规程. 北京: 人民卫生出版社, 2015:18-65.
[5]	中国防痨协会. 耐药结核病化学治疗指南(2015). 中国防痨杂志, 2015, 37(5):421-469. doi:10.3969/j.issn.1000-6621.2015.05.001.
[6]	中华人民共和国国家卫生健康委员会办公厅. 中国结核病预防控制工作技术规范(2020版). 国卫办疾控函〔2020〕279号. 2020-04-02.
[7]	中华人民共和国国家卫生和计划生育委员会. WS 288—2017肺结核诊断. 2017-11-09.
[8]	中华人民共和国国家卫生和计划生育委员会. WS 196—2017结核病分类. 2017-11-09.
[9]	赵雁林, 陈明亭. 中国结核病防治工作技术指南(2021版). 北京: 人民卫生出版社, 2021.
[10]	李仁忠, 阮云洲, 李玉红. 关于世界卫生组织广泛耐药结核病新定义的解读. 中国防痨杂志, 2021, 43(6): 539-541. doi:10.3969/j.issn.1000-6621.2021.06.003.
[11]	肖和平, 方勇, 范琳, 等. 耐药结核病化学治疗研究的过去现状与未来. 中国防痨杂志, 2014, 36(8):634-636. doi:10.3969/j.issn.1000-6621.2014.08.003.
[12]	白桦, 郭婧玮, 胡培磊, 等. 2014—2018年湖南省耐药监测点结核分枝杆菌耐药监测结果分析. 中国防痨杂志, 2021, 43(4): 364-369. doi:10.3969/j.issn.1000-6621.2021.04.012.
[13]	World Health Organization. Compendium of WHO guidelines and associated standards. Geneva: World Health Organization, 2018.
[14]	中华人民共和国国家疾病预防控制局综合司, 中华人民共和国国家卫生健康委员会办公厅. 关于进一步加强耐药结核病防治工作的通知. 国疾控传防发〔2023〕4号. 2023-02-17.
[15]	中华人民共和国国务院办公厅. 国务院办公厅关于印发“十三五”全国结核病防治规划的通知. 国办发〔2017〕16号. 2017-02-06.
[16]	田晓梅, 雷娟, 刘静, 等. 宁夏地区利福平耐药肺结核诊疗管理及筹资模式实施效果分析. 中国防痨杂志, 2021, 43(8): 772-777. doi:10.3969/j.issn.1000-6621.2021.08.004.
[17]	World Health Organization. Programmatic Management of Drug Resistant Tuberculosis. Geneva: World Health Organization, 2017.
[18]	买买提艾力·艾合木提, 黄巧玲, 古尔色曼·阿布拉, 等. 新疆喀什地区1307例肺结核患者行利福平和异烟肼耐药性检测的结果分析. 中国防痨杂志, 2020, 42(11): 1209-1213. doi:10.3969/j.issn.1000-6621.2020.11.012.
[19]	李俊, 张庆玲, 张宇, 等. 2015—2019年湖北省荆州市肺结核患者一线抗结核药品耐药分析. 中国防痨杂志, 2021, 43(5):521-525. doi:10.3969/j.issn.1000-6621.2021.05.020.
[20]	Tiberi S, Utjesanovic N, Galvin J, et al. Drug resistant TB-latest developments in epidemiology, diagnostics and management. Int J Infect Dis, 2022, 124 Suppl 1: S20-S25. doi:10.1016/j.ijid.2022.03.026.
[21]	车贝贝, 王小平, 邱青, 等. 2009—2020年江苏省南通市耐多药/利福平耐药肺结核诊疗服务特征的纵向研究. 中国防痨杂志, 2023, 45(9):864-871. doi:10.19982/j.issn.1000-6621.20230058.
[22]	田晓梅, 沙小兰, 刘晔, 等. 2019—2022年宁夏回族自治区≥65岁老年肺结核疫情及治疗转归特点分析. 中国防痨杂志, 2023, 45(9):857-863. doi:10.19982/j.issn.1000-6621.20230166.
[23]	单灵莺, 刘艳, 王胜难, 等. 上海市普陀区2010—2019年老年人肺结核特征分析. 健康教育与健康促进, 2021, 16(4):363-366. doi:10.16117/j.cnki.31-1974/r.202104363.
[24]	滕人聪, 李涛, 李玉红, 等. 2015—2021年全国65岁及以上老年肺结核患者登记情况分析. 中国防痨杂志, 2023, 45(4): 367-371. doi:10.19982/j.issn.1000-6621.20220494.
[25]	徐彩红, 赵雁林. 从《2020年全球结核病报告》看我国结核病防治工作. 中华传染病杂志, 2021, 39(7): 392-397. doi:10.3760/cma.j.cn311365-20210406-00117.
[26]	王胜芬, 周杨, 欧喜超, 等. 我国结核病耐药状况: 2018年全国结核病耐药监测数据分析. 中国防痨杂志, 2022, 44(11): 1141-1147. doi:10.19982/j.issn.1000-6621.20220268.
[27]	徐静, 姜爽爽, 郑海伦, 等. 290例耐药肺结核高危人群耐药情况及治疗结果分析. 中国防痨杂志, 2023, 45(3):323-327. doi:10.19982/j.issn.1000-6621.20220485.
[28]	Shi W, Davies Forsman L, Hu Y, et al. Improved treatment outcome of multidrug-resistant tuberculosis with the use of a rapid molecular test to detect drug resistance in China. Int J Infect Dis, 2020, 96: 390-397. doi:10.1016/j.ijid.2020.04.049. pmid: 32353546

年份	可疑患者例数^a	活动性肺结核患者例数	肺结核患者例数^b	病原学阳性(例)				病原学阳性率(%)
年份	可疑患者例数^a	活动性肺结核患者例数	肺结核患者例数^b	仅涂片	仅培养	仅分子生物学	小计	病原学阳性率(%)
2015	8082	1562	1562	177	0	0	177	11.33
2016	7889	1726	1726	185	0	0	185	10.72
2017	8376	1625	1625	254	55	0	309	19.02
2018	5416	959	808	236	58	52	346	42.82
2019	4162	901	742	195	39	140	374	50.40
2020	3385	729	607	213	14	124	351	57.83
2021	2959	520	440	169	10	79	258	58.64
2022	2425	436	385	140	16	80	236	61.30
合计	42694	8458	7895	1569	192	475	2236	28.32

耐药谱类型	非高危人群		高危人群		合计
耐药谱类型	例数	耐药率(%)	例数	耐药率(%)	例数	耐药率(%)
RFP	44	26.99	38	25.50	82	26.28
RFP+EMB	6	3.68	2	1.34	8	2.56
RFP+Sm	5	3.07	1	0.67	6	1.92
RFP+Ofx	12	7.36	6	4.03	18	5.77
RFP+EMB+Sm	1	0.61	2	1.34	3	0.96
RFP+INH	44	26.99	29	19.46	73	23.40
RFP+INH+EMB	33	20.25	51	34.23	84	26.92
RFP+INH+Sm	9	5.52	3	2.01	12	3.85
RFP+INH+Ofx	3	1.84	10	6.71	13	4.17
RFP+INH+Km	3	1.84	0	0.00	3	0.96
RFP+INH+Sm+EMB	0	0.00	1	0.67	1	0.32
RFP+INH+Sm+Ofx	1	0.61	4	2.68	5	1.60
RFP+INH+Sm+Km	2	1.23	0	0.00	2	0.64
RFP+INH+Ofx+Km	0	0.00	1	0.67	1	0.32
RFP+INH+Sm+EMB+Ofx	0	0.00	1	0.67	1	0.32
合计	163	100.00	149	100.00	312	100.00