收稿日期: 2023-11-03
网络出版日期: 2024-03-26
基金资助
广东省医学科学技术研究基金项目(B2021012);广州市科技计划项目(202201010785);广东省感染性疾病（结核病）临床医学研究中心(2020B1111170014)
Drug resistance characteristics and treatment strategies of TB patients in three age groups in Guangdong Province from 2014 to 2020
Received date: 2023-11-03
Online published: 2024-03-26
目的 探究2014-2020年广东省期间各年龄段结核病患者的耐药特征与应对防治策略。 方法 以2014-2020年广东省32个结核病耐药监测点中，确诊结核病患者的39 048株结核分枝杆菌（mycobacterium tuberculosis， MTB）临床分离株为研究对象，回顾性分析耐药结核病患者及实验室相关资料，并以年龄、地区进行分组，探讨MTB临床分离株对药物的耐药性趋势、耐药结核病（包括单耐药结核病（monodrug?resistant tuberculosis， MR-TB）、多耐药结核病（poly-resistant tuberculosis， PDR-TB）、耐多药结核病（multidrug?resistant tuberculosis， MDR-TB）和广泛耐药结核病（extensively drug-resistant tuberculosis， XDR-TB）的发病率差异，以及MTB临床分离株对重点药物（利福平和氧氟沙星）的耐药情况。 结果 2014-2020年广东省32个结核病耐药监测点患者MTB临床分离株对9种抗结核药物在不同年度间、不同年龄段间的耐药率差异均无统计学意义（均P > 0.05）。MTB临床分离株的单耐药率、多耐药率、耐多药率、广泛耐药率和总耐药率分别为14.46%、5.16%、4.58%、1.29%。儿童组患者MTB临床分离株单耐药率（15.4%）高于青壮年组及老年组；青壮年组（5.0%）和老年组（5.0%）患者MTB临床分离株耐多药率高于儿童组患者；老年组患者MTB临床分离株广泛耐药率（2.1%）高于儿童组及青壮年组，差异均有统计学意义（P < 0.001）。来自珠三角地区的患者MTB临床分离株的单耐药率（14.8%）、多耐药率（5.3%）、耐多药率（4.7%）、广泛耐药率（1.4%）、耐氧氟沙星率（11.33%）和耐利福平率（6.92%）明显高于非珠三角地区，差异均有统计学意义（P < 0.001）。 结论 根据监测点数据，2014-2020年间，广东省耐药结核病的流行趋势平缓。但在特定人群（如儿童和老年人）中，耐药结核病的发病率较高，且珠三角地区的耐药结核病发病率和重点药物耐药率均高于广东省其他地区，值得进一步关注和采取防控策略。
卓文基 , 魏然 , 陈燕梅 , 陈珣珣 , 余美玲 , 郭卉欣 , 梁鸿迪 , 梁静 , 赖晓宇 . 2014-2020年广东省不同年龄段结核病患者耐药特征及应对防治策略[J]. 实用医学杂志, 2024 , 40(5) : 702 -707 . DOI: 10.3969/j.issn.1006-5725.2024.05.019
Objective To evalute the drug resistance characteristics of tuberculosis（TB） patients of all ages in Guangdong Province during 2014-2020， and provide prevention and treatment strategies of tuberculosis. Method We used 39，048 clinical isolates of Mycobacterium tuberculosis （MTB） belonging to patients with confirmed TB from 2014 to 2020， from 32 TB drug?resistant surveillance sites in Guangdong Province， and we retrospectively analyzed the laboratories data of patients with drug?resistant TB， and grouped patients by age and region， to explore the trend of drug?resistance of MTB clinical isolates， the trend and incidence differences of multi?resistant TB （including monodrug?resistant TB （MR?TB）， polydrug?resistant TB （PDR?TB）， multidrug?resistant TB （MDR?TB） and extensively drug?resistant TB （XDR?TB））， and resistance characteristics of MTB clinical isolates to drugs in focus （rifampicin and ofloxacin）. Result The differences in the resistance rates of MTB clinical isolates to nine antituberculosis drugs among patients at 32 TB drug resistance surveillance sites in Guangdong Province from 2014 to 2020 were not statistically significant （P > 0.05）. The rates of MR?TB， PDR?TB， MDR?TB， XDR?TB， and total resistance isolates of MTB clinical isolates were 14.46%， 5.16%， 5.16%， 4.58%， and 1.29%， respectively. he pediatric group had a higher MR rate （15.4%） than the adult and geriatric groups， while the adult and geriatric groups had higher MDR rates （5.0% and 5.0%， respectively）. The geriatric group also had a higher XDR rate （2.1%）， with statistically significant differences （P < 0.001）. The rates of MR?TB （14.8%）， PDR?TB （5.3%）， MDR?TB （4.7%）， XDR?TB （1.4%）， ofloxacin resistance （11.33%） and rifampicin resistance （6.92%） of MTB clinical isolates were higher in patients from the Pearl River Delta than in other regions of Guangdong Province， with statistically significant differences （P < 0.001）. Conclusion According to the data from the surveillance sites， the epidemiological trend of drug?resistant TB in Guangdong Province is leveling off during the period 2014?2020. However， the incidence of drug?resistant TB is higher in specific populations （e.g. children and the elderly）， and the incidence of drug?resistant TB and the rate of drug resistance to drugs in focus are higher in the Pearl River Delta than in other regions of Guangdong Province， necessitating further investigation and the development of novel prevention and control strategies.
| 1 | BAGCCHI S. WHO's Global Tuberculosis Report 2022［J］. Lancet Microbe， 2023，4（1）：e20. doi:10.1016/s2666-5247(22)00359-7 |
| 2 | CHEN Y， LIU J， ZHANG Q， et al.Epidemiological features and temporal trends of HIV-negative tuberculosis burden from 1990 to 2019： a retrospective analysis based on the Global Burden of Disease Study 2019［J］. BMJ Open， 2023，13（9）：e074134. doi:10.1136/bmjopen-2023-074134 |
| 3 | DOMíNGUEZ J， BOEREE M J， CAMBAU E，et al. TBnet and RESIST-TB networks. Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis： a 2023 TBnet/RESIST-TB consensus statement［J］. Lancet Infect Dis， 2023，23（4）：e122-e137. doi:10.1016/s1473-3099(22)00875-1 |
| 4 | 赵雁林， 逢宇. 结核病实验室检验规程［M］. 北京：人民卫生出版社， 2015：18-65. |
| 5 | World Health Organization. Technical manual for drug susceptibility testing of medicines used in the treatment of tuberculosis［M］. Global Tuberculosis Programme， 2018. |
| 6 | VINEY K， LINH N N， GEGIA M， et al. New definitions of pre-extensively and extensively drug-resistant tuberculosis： update from the World Health Organization［J］. Eur Respir J， 2021，57（4）：2100361. doi:10.1183/13993003.00361-2021 |
| 7 | MENZIES R， HOPEWELL K， NUNN P， et al. Monitoring During Treatment in： Treatment of Tuberculosis Guidelines. 4 Ed［C］. TNO， 2010. |
| 8 | 田鹏，李娜娜，刘梅，等. 遵义地区303例肺结核患者微孔板药敏结果的耐药模式分析［J］. 遵义医科大学学报， 2023，46（7）：684-691. |
| 9 | 马广仁，曹佳伟，林梅，等. 青岛市结核病患者2016-2021年结核分枝杆菌耐药情况分析［J］. 精准医学杂志， 2022，37（5）：418-421. |
| 10 | MUSHTAQ F， RAZA S M， AHMAD A， et al. Antimicrobial drug resistant features of Mycobacterium tuberculosis associated with treatment failure［J］. PLoS One， 2023，18（10）：e0293194. doi:10.1371/journal.pone.0293194 |
| 11 | GHODOUSI A， TAGLIANI E， KARUNARATNE E， et al. Isoniazid Resistance in Mycobacterium tuberculosis Is a Heterogeneous Phenotype Composed of Overlapping MIC Distributions with Different Underlying Resistance Mechanisms［J］. Antimicrob Agents Chemother， 2019，63（7）：e00092-19. doi:10.1128/aac.00092-19 |
| 12 | YUEN L K， LESLIE D， COLOE P J. Bacteriological and molecular analysis of rifampin-resistant Mycobacterium tuberculosis strains isolated in Australia［J］. J Clin Microbiol， 1999，37（12）：3844-3850. doi:10.1128/jcm.37.12.3844-3850.1999 |
| 13 | WILLIAMS D L， SPRING L， COLLINS L， et al. Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis［J］. Antimicrob Agents Chemother， 1998，42（7）：1853-1857. doi:10.1128/aac.42.7.1853 |
| 14 | REKART M L， AUNG A， CULLIP T， et al. Household drug-resistant TB contact tracing in Tajikistan［J］. Int J Tuberc Lung Dis， 2023，27（10）：748-753. doi:10.5588/ijtld.23.0066 |
| 15 | VERMA A K， YADAV R N， KUMAR G， et al. Multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis strains in geriatrics： An analysis and its implications in tuberculosis control［J］. J Clin Tuberc Other Mycobact Dis， 2022，27：100317. doi:10.1016/j.jctube.2022.100317 |
| 16 | AN Q， SONG W， LIU J， et al. Primary Drug-Resistance Pattern and Trend in Elderly Tuberculosis Patients in Shandong， China， from 2004 to 2019［J］. Infect Drug Resist， 2020，13：4133-4145. doi:10.2147/idr.s277203 |
| 17 | SHARLING L， MARKS S M， GOODMAN M， et al. Rifampin-resistant Tuberculosis in the United States， 1998-2014［J］. Clin Infect Dis， 2020，70（8）：1596-1605. doi:10.1093/cid/ciz491 |
| 18 | ROELENS M， BATTISTA MIGLIORI G， ROZANOVA L， et al. Evidence-based Definition for Extensively Drug-Resistant Tuberculosis［J］. Am J Respir Crit Care Med， 2021，204（6）：713-722. doi:10.1164/rccm.202009-3527oc |
| 19 | CHE Y， SONG Q， YANG T， et al. Fluoroquinolone resistance in multidrug-resistant Mycobacterium tuberculosis independent of fluoroquinolone use［J］. Eur Respir J， 2017，50（6）：1701633. doi:10.1183/13993003.01633-2017 |
| 20 | MIRZAYEV F， VINEY K， LINH N N， et al. World Health Organization recommendations on the treatment of drug-resistant tuberculosis， 2020 update［J］. Eur Respir J， 2021，57（6）：2003300. doi:10.1183/13993003.03300-2020 |
| 21 | HAMEED H M A， TAN Y， ISLAM M M， et al. Phenotypic and genotypic characterization of levofloxacin- and moxifloxacin-resistant Mycobacterium tuberculosis clinical isolates in southern China［J］. J Thorac Dis， 2019，11（11）：4613-4625. doi:10.21037/jtd.2019.11.03 |
| 22 | MODONGO C， BARILAR I， WANG Q， et al. Tuberculosis Variant with Rifampin Resistance Undetectable by Xpert MTB/RIF， Botswana［J］. Emerg Infect Dis， 2023，29（11）：2403-2406. doi:10.3201/eid2911.230987 |
/
| 〈 |
|
〉 |