679株结核分枝杆菌药敏结果分析

目的:了解衢州地区结核分枝杆菌耐药情况,指导临床医生合理选择抗结核药物和制定个性化的治疗方案。方法:采用比例法对694株痰培养阳性菌株进行一线抗结核药物异烟肼(INH)、利福平(REF)、链霉素(SM)、乙胺丁醇(EMB)和二线药物卡那霉素(KM)、氧氟沙星(OFX)的耐药性检测,利用鉴别培养基对分枝杆菌进行初步菌种鉴定。结果:679株结核分枝杆菌药敏的总耐药率21%,耐多药率5.2%,六种抗结核药物的耐药情况分别是异烟肼12.67%,链霉素10.46%、氧氟沙星7.95%、利福平6.19%、乙胺丁醇2.36%、卡那霉素2.06%.复治病人的总耐药率、耐多药率和单药耐药率明显高于初治病人。结论:应加强肺结核初治病人的规范化治疗,加大对复治结核病人的治疗和管理,预防耐药病人尤其是耐多药病人的产生和传播。     

The population structure of drug-resistant Mycobacterium tuberculosis clinical isolates from Sichuan in China

China ranks second next to India among 22 high-burden countries despite decades' effort on tuberculosis (TB) control. The Sichuan province today contains the second-largest number of TB cases among Chinese provinces, where the prevalence of drug-resistant TB, especially MDR-TB, is much higher than the average level in eastern China. In this study, the population structure and the transmission characteristics of drug-resistant TB in Sichuan province were studied by spoligotyping and 24-locus Mycobacterial interspersed repetitive units-variable number tandem DNA repeats (MIRU-VNTR), applied to a total of 306 clinical isolates. Spoligotyping-based analysis showed that Beijing family represented 69.28% of all isolates and constituted the largest group (66.24%) of MDR-TB in Sichuan. The remaining isolates, accounting for 33.76% of MDR isolates, belonged to the ill-defined T family, Manu2, H3, LAM9, and other minor unassigned clades. The discriminatory power evaluated for spoligotyping was poor (HGI=0.595), but high for 24-locus MIRU-VNTRs (HGI=0.999). The number of the most discriminatory loci (h>0.6) was 12, including locus 424, 802, 960, 1644, 1955, 2163b, 2996, 3007, 3192, 3690, 4348 and 4052. It was concluded that 24-locus MIRU-VNTRs could be a more discriminatory tool for differentiating clinical isolates from Sichuan region. The small clustering size obtained from the current population structure analysis suggested that the high prevalence of drug-resistant TB in this region might be attributed partially to the acquired resistance due to inappropriate drug use rather than active transmission of drug-resistant TB (primary resistance).     

河南省1 074株结核分枝杆菌药敏特征分析

目的 了解河南省肺结核患者的耐药情况,为制定耐药结核病防控策略提供参考依据。方法 收集2018年河南省25个县（市、区）结核病定点医疗机构分离的结核分枝杆菌,采用《结核分枝杆菌药物敏感性试验标准化操作程序及质量保证手册》中的比例法,开展对异烟肼（INH）、利福平（RFP）、链霉素（SM）、乙胺丁醇（EMB）、氧氟沙星（OFX）、卡那霉素（KM）、卷曲霉素（CPM）、对氨基水杨酸（PAS）、丙硫异烟胺（PTO）9种抗结核药物的敏感度试验,分析菌株的耐药情况。结果 结核分枝杆菌1 074株,总耐药率为26.07%（280/1 074）,单耐药146株（13.59%）,耐多药61株（5.68%）,多耐药73株（6.8%）,广泛耐药9株（0.84%）;一线药物耐药以SM（15.64%）、INH（12.29%）为主,二线药物耐药以OFX（5.4%）、KM（4%）为主。初治患者对一线药物INH、RFP、EMB、SM的耐药率均低于复治患者（χ2 = 31.754,49.153,50.524,10.499;P＜0.001,0.001,0.001,P = 0.001）,初治患者中对二线药物KM和PAS的耐药率低于复治患者（χ2 = 4.569,5.655;P = 0.033,0.017）;72例RFP耐药的患者中,61例（84.7%）患者同时耐INH（即耐多药,MDR）,在所有的61例MDR肺结核患者中,初治患者占52.46%（32/61）。OFX耐药率（32.79%）高于CPM耐药率（11.48%）和OFX、CPM同时的耐药率（9.84%）（χ2 =13.531,P = 0.001）,我省在使用OFX和CPM治疗肺结核患者时应加强用药规范性。结论 河南省结核分枝杆菌的总耐药、耐多药、OFX和CPM的耐药情况较为严重,应加强防控措施,以减少耐药结核病的产生和传播。     

Epidemiology of Primary Multidrug-Resistant Tuberculosis,Vladimir Region,Russia

We studied the epidemiology of drug-resistant tuberculosis (TB) in Vladimir Region, Russia, in 2012. Most cases of multidrug-resistant TB (MDR TB) were caused by transmission of drug-resistant strains, and >33% were in patients referred for testing after mass radiographic screening. Early diagnosis of drug resistance is essential for preventing transmission of MDR TB.     

河北省五市结核分枝杆菌耐药情况及耐多药菌株对利奈唑胺的敏感性

目的了解河北省结核分枝杆菌耐药情况,以及耐多药结核分枝杆菌对利奈唑胺的敏感性,指导临床治疗耐多药结核病。方法收集河北省五市六所医院2016年1—12月974例结核病患者分离菌株及患者临床信息,检测结核分枝杆菌对抗结核药物异烟肼(INH)、利福平(RFP)、链霉素(SM)、乙胺丁醇(EMB)、氧氟沙星(OFX)、卡那霉素(KM)的敏感性,采用分层随机法选取100株耐多药结核分枝杆菌,检测其对利奈唑胺的敏感性。结果结核病初治患者的耐药率和耐多药率分别为26.6%(200/753)和13.5%(102/753),复治患者的耐药率和耐多药率分别为59.7%(132/221)和53.4(118/221),复治患者耐药率和耐多药率均高于初治患者(χ~2值分别为83.7、93.5,均P0.01)。一线抗结核药物INH、RFP、SM和EMB的耐药率分别为25.8%、23.7%、16.7%和7.1%;二线抗结核药物OFX和KM的耐药率为4.7%(37/782)和4.0%(31/782);耐多药结核分枝杆菌对利奈唑胺的敏感率为80.8%(59/73)。结论结核病复治患者耐药率和耐多药率高于初治患者,利奈唑胺体外对耐多药结核分枝杆菌具有良好的抗菌活性。     

吉林省复治涂阳结核病患者分离株耐药谱研究

目的分析吉林省复治涂阳结核病患者的耐药谱资料,为耐药结核病防治工作提供参考依据。方法采用随机抽样的方法,选取吉林省30个监测点630例复治涂阳结核病患者,采用比例法对分离的结核分枝杆菌菌株进行鉴定及药敏试验,分析结核分枝杆菌的获得性耐药情况及影响因素。结果纳入复治涂阳患者630例,培养阳性597例,阳性率为94.8%;获得性耐药率为53.94%;获得性耐多药率为23.12%。结论吉林省结核病患者的耐药率日益趋高,复治患者是主要的耐药人群,应加强耐药结核病监测,有效预防和控制耐药结核病的产生和蔓延。     

Clusters of Drug-Resistant Mycobacterium tuberculosis Detected by Whole-Genome Sequence Analysis of Nationwide Sample,Thailand, 2014–2017

Multidrug-resistant tuberculosis (MDR TB), pre-extensively drug-resistant tuberculosis (pre-XDR TB), and extensively drug-resistant tuberculosis (XDR TB) complicate disease control. We analyzed whole-genome sequence data for 579 phenotypically drug-resistant M. tuberculosis isolates (28% of available MDR/pre-XDR and all culturable XDR TB isolates collected in Thailand during 2014–2017). Most isolates were from lineage 2 (n = 482; 83.2%). Cluster analysis revealed that 281/579 isolates (48.5%) formed 89 clusters, including 205 MDR TB, 46 pre-XDR TB, 19 XDR TB, and 11 poly–drug-resistant TB isolates based on genotypic drug resistance. Members of most clusters had the same subset of drug resistance-associated mutations, supporting potential primary resistance in MDR TB (n = 176/205; 85.9%), pre-XDR TB (n = 29/46; 63.0%), and XDR TB (n = 14/19; 73.7%). Thirteen major clades were significantly associated with geography (p<0.001). Clusters of clonal origin contribute greatly to the high prevalence of drug-resistant TB in Thailand.     

Worldwide emergence of extensively drug-resistant tuberculosis

Mycobacterium tuberculosis strains that are resistant to an increasing number of second-line drugs used to treat multidrug-resistant tuberculosis (MDR TB) are becoming a threat to public health worldwide. We surveyed the Network of Supranational Reference Laboratories for M. tuberculosis isolates that were resistant to second-line anti-TB drugs during 2000-2004. We defined extensively drug-resistant TB (XDR TB) as MDR TB with further resistance to > or = 3 of the 6 classes of second-line drugs. Of 23 eligible laboratories, 14 (61%) contributed data on 17,690 isolates, which reflected drug susceptibility results from 48 countries. Of 3,520 (19.9%) MDR TB isolates, 347 (9.9%) met criteria for XDR TB. Further investigation of population-based trends and expanded efforts to prevent drug resistance and effectively treat patients with MDR TB are crucial for protection of public health and control of TB.     

2014 - 2017年新余市结核病耐药特征及影响因素分析

目的 了解新余市耐药结核病的流行特征及其影响因素,为耐药结核病防治和管理提供科学依据。方法 2014 - 2017年新余市所有涂阳肺结核病人痰标本进行培养,用比例法进行药敏试验,用SPSS 19.0进行数据分析。结果 新余市2014 - 2017年涂阳结核病标本340例,其中6.47%（22例）为非结核分枝杆菌,93.53%（318例）为结核分枝杆菌。结核分枝杆菌的总耐药率20.44%（65例）,单耐药率6.60%（21例）,多耐药率4.09%（13例）,耐多药率9.75%（31例）。初治病人耐药率15.44%（42/272）,复治病人耐药率50.00%（23/46）。年龄(OR = 1.023,95%CI = 1.006～1.040) 、吸烟史(OR = 2.126,95%CI = 1.111～4.067)、居住农村(OR = 0.468,95%CI = 0.233～0.938)和抗结核病治疗史(OR = 4.580,95%CI = 2.291～9.158)是新余市结核病发生耐药的主要影响因素。结论 新余市结核病耐药形势严峻,结核病耐药率和耐多药率均显著高于世界平均水平,耐多药结核菌株中以同时耐6种药物为主。应提高初治病人的治愈率和加强耐药结核病防控工作。     

Multidrug- and extensively drug-resistant tuberculosis, Germany

We evaluated risk factors and treatment outcomes associated with multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) in Germany in 2004-2006. In 177 (4%) of 4,557 culture-positive TB cases, Mycobacterium tuberculosis isolates were identified as MDR TB; an additional 7 (0.15%) met criteria for XDR TB. Of these 184 patients, 148 (80%) were born in countries of the former Soviet Union. In patients with XDR TB, hospitalization was longer (mean +/- SD 202 +/- 130 vs. 123 +/- 81 days; p = 0.015) and resistance to all first-line drugs was more frequent (36% vs. 86%; p = 0.013) than in patients with MDR TB. Seventy-four (40%) of these 184 patients received treatment with linezolid. Treatment success rates ranged from 59% for the entire cohort (59% for MDR TB and 57% for XDR TB) to 87% for those with a definitive outcome (n = 125; 89% for MDR TB and 80% for XDR TB). Extensive drug susceptibility testing and availability of second- and third-line drugs under inpatient management conditions permit relatively high treatment success rates in MDR- and XDR TB.     

福建省结核病耐药性监测结果分析

目的通过开展福建省结核病耐药监测点监测,了解结核病耐药状况,为制订结核病控制对策提供依据。方法对福建省9个设区市的9个监测点2008年9月-2009年8月门诊新登记涂阳患者分离的结核分枝杆菌复合群,采用WHO/IUATLD推荐的比例法进行异烟肼、链霉素、利福平和乙胺丁醇耐药性检测。结果共1 014例病例纳入监测分析,总体耐药率为19.8%,耐多药率为4.6%,其中初始耐药率为17.9%,初始耐多药率为3.4%,获得性耐药率为44.0%,获得性耐多药率为20.0%。结论福建省结核病耐药监测点耐药率低于全国平均水平,但高于国际平均水平,今后仍要进一步加强耐药结核病的防治工作。     

实施DOTS策略后合肥市结核病人耐药性分析

目的 了解合肥市实施DOTS策略后肺结核病例的耐药状况,为制定控制耐药结核病提供科学依据.方法 对合肥市疾病预防控制中心结核病门诊2009年2月～2010年1月392例培养阳性病例进行菌型鉴定,获得352例结核分枝杆菌并对其进行异烟肼、利福平、链霉素、乙胺丁醇等药物敏感性鉴定.结果 352例结核分枝杆菌中总耐药率及耐多药率分别是20.5％和3.1％.初始耐药率为16.3％,初始耐多药率为1.9％;其获得性耐药率为52.5％,获得性耐多药率为12.5％.复治病人的耐药率明显高于新病人;耐药率最高的是SM 25％.结论 合肥市总耐药率和耐多药率低于全国耐药基线调查结果,但控制结核分枝杆菌耐药形势刻不容缓,今后要加强对新发男性青壮年病人的管理措施,提高病例的依从性和治愈率.     

Revised Definitions of Tuberculosis Resistance and Treatment Outcomes,France, 2006–2019

Definitions of resistance in multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant tuberculosis (XDR TB) have been updated. Pre–XDR TB, defined as MDR TB with additional resistance to fluoroquinolones, and XDR TB, with additional resistance to bedaquiline or linezolid, are frequently associated with treatment failure and toxicity. We retrospectively determined the effects of pre-XDR/XDR TB resistance on outcomes and safety of MDR TB treatment in France. The study included 298 patients treated for MDR TB at 3 reference centers during 2006–2019. Of those, 205 (68.8%) cases were fluoroquinolone-susceptible MDR TB and 93 (31.2%) were pre-XDR/XDR TB. Compared with fluoroquinolone-susceptible MDR TB, pre-XDR/XDR TB was associated with more cavitary lung lesions and bilateral disease and required longer treatment. Overall, 202 patients (67.8%) had favorable treatment outcomes, with no significant difference between pre-XDR/XDR TB (67.7%) and fluoroquinolone-susceptible MDR TB (67.8%; p = 0.99). Pre-XDR/XDR TB was not associated with higher risk for serious adverse events.     

鄞州区结核分枝杆菌耐药性研究

目的了解鄞州区肺结核患者结核分枝杆菌的耐药水平,为本区的结核病诊治提供参考依据。方法对鄞州区疾病预防控制中心2008—2009年收集的结核分枝杆菌用WHO推荐的比例法进行异烟肼(H)、利福平(R)、链霉素(S)和乙胺丁醇(E)的耐药性检测。结果 299例初复治患者的痰培养分离的结核分枝杆菌,总耐药率为30.77%,初始耐药率和获得性耐药率分别为27.48%和54.05%;耐多药率为6.69%,其中初始和获得性耐多药率分别为4.20%和24.32%。4种抗结核药物的耐药率由高到低分别为异烟肼(19.40%)、链霉素(16.05%)、利福平(9.36%)和乙胺丁醇(6.02%)。不同性别、年龄、户籍的耐药率差异无统计学意义。结论鄞州区结核病耐药形势依然严峻,应继续加强结核病的防治工作。     

Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs--worldwide, 2000-2004

During the 1990s, multidrug-resistant (MDR) tuberculosis (TB), defined as resistance to at least isoniazid and rifampin, emerged as a threat to TB control, both in the United States and worldwide. MDR TB treatment requires the use of second-line drugs (SLDs) that are less effective, more toxic, and costlier than first-line isoniazid- and rifampin-based regimens. In 2000, the Stop TB Partnership's Green Light Committee was created to increase access to SLDs worldwide while ensuring their proper use to prevent increased drug resistance. While assisting MDR TB treatment programs worldwide, the committee encountered reports of multiple cases of TB with resistance to virtually all SLDs. To assess the frequency and distribution of extensively drug-resistant (XDR) TB cases, CDC and the World Health Organization (WHO) surveyed an international network of TB laboratories. This report summarizes the results of that survey, which determined that, during 2000-2004, of 17,690 TB isolates, 20% were MDR and 2% were XDR. In addition, population-based data on drug susceptibility of TB isolates were obtained from the United States (for 1993-2004), Latvia (for 2000-2002), and South Korea (for 2004), where 4%, 19%, and 15% of MDR TB cases, respectively, were XDR. XDR TB has emerged worldwide as a threat to public health and TB control, raising concerns of a future epidemic of virtually untreatable TB. New anti-TB drug regimens, better diagnostic tests, and international standards for SLD-susceptibility testing are needed for effective detection and treatment of drug-resistant TB.     

Clonal Expansion of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis, Japan

The emergence and spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has raised public health concern about global control of TB. To estimate the transmission dynamics of MDR and XDR TB, we conducted a DNA fingerprinting analysis of 55 MDR/XDR Mycobacterium tuberculosis strains isolated from TB patients throughout Japan in 2002. Twenty-one (38%) of the strains were classified into 9 clusters with geographic links, which suggests that community transmission of MDR/XDR TB is ongoing. Furthermore, the XDR M. tuberculosis strains were more likely than the non–XDR MDR strains to be clustered (71% vs. 24%; p = 0.003), suggesting that transmission plays a critical role in the new incidence of XDR TB. These findings highlight the difficulty of preventing community transmission of XDR TB by conventional TB control programs and indicate an urgent need for a more appropriate strategy to contain highly developed drug-resistant TB.     

Drug susceptibility profile of Mycobacterium tuberculosis isolated from HIV infected and uninfected pulmonary tuberculosis patients in Eastern India

HIV is driving the tuberculosis (TB) epidemic in many developing countries including India. This study was initiated to determine the drug resistance pattern of pulmonary TB among 200 HIV seropositive and 50 HIV negative hospitalized patients from different states of Eastern India. The TB positive isolates (120) were screened and characterized by conventional laboratory methods followed by first- and second-line drug susceptibility testing on Lowenstein-Jensen medium by the proportion method. The drug susceptibility testing showed 17.7% (16/90) and 6.6% (2/30) multidrug-resistant (MDR) TB for the HIV positive and HIV negative patients, respectively. 22.2% (4/18) of the isolated MDR-TB cases could be classified as extensively drug-resistant (XDR) TB isolates. 88.8% (16/18) of all the MDR-TB isolates and all XDR-TB isolates were screened from HIV patients. Five (27.7%) of the 18 MDR-TB isolates showed resistance to all the first-line drugs. Mortality rate among the XDR-TB isolates was as high as 75% (3/4). Patients with interrupted anti-TB drug treatment were the ones most affected. These findings are critical and the risk to public health is high, particularly with HIV infected patients.     

四川省自贡市结核分枝杆菌耐药性监测结果初步分析

目的了解自贡市结核分枝杆菌的耐药状况及其影响因素,为制定耐药结核的防治对策提供科学的依据。方法对全市各区县结核病防治机构2010年4月至2011年8月从肺结核患者分离培养的阳性菌株进行菌型鉴定及采用比例法对8种抗结核药物(INH、SM、RFP、EMB、KM、AMK、CPM和OFLX)进行药物敏感性测定。结果本研究组共对285株结核分枝杆菌临床分离菌株进行了药物敏感性检测,总耐药率为27.02%(77/285),其中初治患者菌株耐药率为21.94%(52/237),复治患者菌株耐药率为52.08%(25/48);总的耐多药率为11.58%(33/285),其中初治患者菌株耐多药率为6.33%(15/237),复治患者菌株耐多药率为37.50%(18/48),对8种抗结核药物INH、RFP、OFLX、SM、EMB、KM、AMK和CPM的耐药率分别为17.19%、12.98%、11.93%、11.23%、5.61%、0.35%、0.35%和0%;耐单药者31例(10.88%),耐2药20例(7.02%),耐3种及以上药者26例(9.12%)。结论本次耐药监测结果表明自贡市结核分枝杆菌耐药率处于较高的水平,耐药菌传播较为严重,应进一步加强耐药结核病的监测和防治。     

2012-2015年长沙地区肺结核患者结核分枝杆菌耐药状况分析

摘要:目的 了解长沙地区结核分枝杆菌耐药情况。方法 分析某院2012年1月至2015年10月分离的6 198株结核分枝杆菌对9种抗结核药物的耐药情况。结果 6 198株结核分枝杆菌复合群菌株耐药率顺位前5位依次为INH(14.18％)、RFP(13.57%)、SM(12.31％)、EMB(3.87%)、OFLX(2.60%);总耐药率为20.56%,耐多药占9.31%,多耐药占4.52%,广泛耐药占0.45%;除2012年20岁以下年龄组女性耐药结核菌的检出率略高于男性外,其余年份各年龄组男性均高于女性;复治患者的耐药率(24.76%)高于初治患者(19.49%),两者差异有统计学意义(χ2=176.21,P<0.001）;结论 院结核分枝杆菌耐药率总体低于全国第五次结核病流行病学调查结果,但耐多药率高于全国水平,耐药状况仍然严峻。     

2017-2018年西安市结核病耐药流行状况及相关因素分析

目的 了解西安市结核分枝杆菌耐药情况及耐药产生的影响因素,为结核病的防治提供科学依据。方法 将2017-2018年西安市14个区(县)结核病门诊和西安市胸科医院所有初治及复治痰结核分枝杆菌培养阳性的病例作为研究对象,进行4种一线抗结核药物的敏感性试验。采用χ2检验和Fisher精确概率法对初治组和复治组的耐药率进行比较,用非条件Logistic模型进行相关因素分析。结果 西安市结核分枝杆菌总耐药率为39.0%,初治组耐药率为34.9%,复治组耐药率为73.8%;耐多药率为24.4%,初治组耐多药率为19.3%,复治组耐多药率为68.6%;耐药率与耐多药率均为复治组明显高于初治组,差异有统计学意义(耐药率:χ2=98.145,P＜0.001;耐多药率:χ2=202.891,P＜0.001)。结论 西安市结核分枝杆菌耐药水平较高,特别是耐多药患者的增多,耐药形势依然严峻,有必要加强抗结核药物耐药性的监测,并采取有效的措施控制耐药菌的传播;经多因素非条件Logistic逐步回归分析,年龄、性别、民族、职业及治疗史都是影响西安市结核患者耐药的独立因素。