1996-2001年住院复治肺结核患者结核分枝杆菌耐药性的调查

目的 探讨住院复治肺结核患者的耐药情况.方法 对1996-2001年培养阳性的1385例住院肺结核患者中440例复治肺结核患者的耐药情况按年龄分组进行回顾性分析.结果 总耐药率以青年组最高.耐2药及以上者比例较耐1药比例高,青年组耐R率明显高于老年组;耐2药中,以耐HR占首位.总的耐多药率为49.5%,青年组高达73.9%.结论 复治肺结核患者的高耐药率应引起足够重视,需采取更多措施降低耐药率.     

分枝杆菌感染状况和结核分枝杆菌耐药性分析

目的了解本地区就诊患者分枝杆菌感染状况和结核分枝杆菌耐药情况。方法用对患者标本进行分枝杆菌培养鉴定和药敏试验。结果 9653份标本分枝杆菌培养阳性2759例,其中1229株分枝杆菌行菌种鉴定和药敏试验,非结核分枝杆菌219株,结核分枝杆菌1010株,纳入929株药敏结果进行分析,对4种一线抗结核药物至少耐一药232株,耐二药51株、耐三药49株,耐四药33株,耐多药92株。结论本地区分枝杆菌非肺部感染应引起高度重视,结核菌总耐药率和耐多药率近几年维持在稳定高位,结核菌耐药情况仍然十分严重。     

长治市1995—2004年结核分枝杆菌继发耐药性观察

为了解长治市结核分枝杆菌继发耐药趋势,对1995—2004年10年间继发耐药性的检测结果进行了回顾性分析总结,并从继发耐药性的变化趋势中阐明和评价长治市结核病控制工作的效果。     

结核分枝杆菌耐乙胺丁醇的研究进展

结核病是主要经呼吸道传播引起的全身慢性传染病。自20世纪80年代起，结核疫情再次抬头。2001—2003年问以及近期我国传染病监测结果显示，结核病发病人数一直居各种传染病的首位，我国结核病疫情仅次于印度居世界第二位。全国约有5．5亿人感染结核病菌，约450万人患结核病，200万人是开放性结核病，每年因结核死亡的人数达13万。回顾性调查结果表明，我国的总耐药率为27．8％，初始耐药率和获得耐药率分别为18．6％和46．5％，耐多药率为10．7％，其中初始和获得性耐多药率分别为7．6％和17．1％。耐药结核病逐年增多，尤其是多耐药结核病的流行，成为抗结核治疗的难点及治疗失败的主要原因而受到关注。因此，各国在开发新药的过程中对耐药机制的研究就成为一个重要方面。分子生物学及其相关技术的发展，为在分子水平研究提供了良好的技术平台，并且取得了突出的成果。     

宁波市2007年结核分枝杆菌耐药性监测情况分析

耐药结核病,尤其是耐多药结核病对结核病控制产生了严重的威胁^[1]。宁波市从20世纪90年代开始实施了“卫生部加强与促进结核病控制项目”。项目实施的10多年,取得了一定的效果^[2]。宁波市2007年新登记活动性肺结核1664例(包括宁波市本地人口和外来流动人口),进行痰培养的为980例,培养阳性的为930例。市结防所参比实验室对308株培养阳性菌株进行了药敏实验和菌型鉴定并对结果进行分析,为进一步完善宁波市的结核病控制策略提供科学依据。     

深圳市罗湖区1999～2007年肺结核病人耐药监测分析

目的了解深圳市罗湖区结核分枝杆菌的耐药状况。方法连续收集1999～2007年间纳入耐药检测的初治涂阳及复治涂阳病例的药敏试验结果。结果共监测病例1053例,培养生长结核分枝杆菌1005例,耐药211例,耐药率21.0%。其中初治耐药率20.8%,获得性耐药率26.5%,χ2=0.636,P0.5,无统计学意义;耐单药率、耐多药率分别为12.8%,3.9%;耐单药率及耐单药频度均以耐SM最高。结论结核杆菌耐药情况严峻,必须加大DOTS管理策略,合理规则用药,并做好耐药监测工作,提高耐药性结核的治疗水平。     

DOTS-Plus实施后1995-2000年香港地区结核分枝杆菌的二线药物敏感性监测

目的：确定有抗结核治疗史病人在实施“DOTS-Plus”项目后结核分枝杆菌对二线抗结核药物敏感性的变化趋势。方法：对结核分枝杆菌中心实验室过去8年间的全部培养阳性病例的记录进行回顾性调查。药敏试验使用绝对浓度法。对于有抗结核治疗史病人的分离株进一步分析其对一线和二线抗结核药物敏感性变化趋势。结果：在1921例有抗结核治疗史的培阳病人中，1425例(74．2％)对所有4种一线药物均敏感，而176例(9．2％)为耐多药(MDR-TB)。MDR-TB组中，101例(57．4％)对所有二线药物均敏感，而30例(17．0％)对3种及3种以上二线药物耐药。结论：在实施DOTS-Plus项目的情况下，由于严格控制二线抗结核药物的使用，因此复治病例中的MDR-TB比例比较低，在DOTS-Plus执行较好的人群中未见超强耐药株产生。鉴于大多数复治病例仍敏感并且存在较好的MDR实验室检测支持情况下，一线抗结核药用于复治是可行的。     

链霉素耐药结核分枝杆菌临床分离株gidB基因突变研究

目的 探索gidB基因突变在结核分枝杆菌链霉素耐药中的作用.方法 结核分枝杆菌临床分离株中,60株为链霉素耐药,30株敏感.同时进行链霉素MIC测定并采用DNA测序法分析gidB,rpsL和rrs基因突变.结果 20%的耐药株含有gidB单基因突变,80%的耐药株除gidB基因突变以外,还有rpsL或rrs基因突变.敏感株中也有gidB基因突变.gidB突变呈散在分布,未发现突变热点.结论 gidB基因突变在结核分枝杆菌链霉素耐药中的作用尚不能肯定.     

筛选结核分枝杆菌CFP-10抗原适体的研究

目的 建立SELEX技术筛选结核分枝杆菌CFP-10抗原适体的方法,并获得CFP-10 的高亲和性适体.方法 体外构建长度为78个碱基的随机单链DNA(ssDNA)文库,以微孔板为筛选介质,采用SELEX 技术筛选获得CFP-10的适体库.将适体库克隆、测序,用DNAMAN软件对其结构进行分析,利用酶联寡核苷酸吸附试验(enzyme-linked oligonucleotide sorbent assay,ELOSA)测定亲和力.结果 构建的ssDNA文库经过14轮筛选与CFP-10亲和力从0.273提高到1.265;克隆子测序,大多数长度与预期值相符.二级结构显示,口袋和茎环结构可能是适体与CFP-10结合的结构基础.结论 成功建立了SELEX筛选技术,并初步获得了CFP-10的高亲和性适体.     

老年肺结核病人耐药性调查

目的了解住院老年肺结核患者的耐药情况。方法对2005年12月～2006年12月培养阳性的122例住院老年肺结核患者的耐药情况按初治、复治分组,并进行回顾性分析。结果耐药率复治组明显高于初治组,耐单药率以耐INH较高,耐2种药中以耐HS占首位。结论老年肺结核的耐药情况相当严重,应给予足够的重视。     

2000年中国结核病流行病学抽样调查菌株分子流行病学特征

目的:判定北京基因型结核分枝杆菌在中国结核分枝杆菌复合群中的群结构特征。设计:采用spoligotyping和IS6110限制性片段长度多态性(RFLP)方法对441株分枝杆菌分离株行基因分型鉴定。分离株取自2000年中国结核病流行病学抽样调查,耐药性和流行病学资料已知。结果:spoligotyping法共鉴定408株结核分枝杆菌,其中北京基因型结核分枝杆菌占64.9%(265/408)。卡方检验北京基因型结核分枝杆菌在性别、年龄、地区所占的比例没有统计学显著性差异,但是耐多药(MDR)有统计学显著性差异。北京基因型在耐多药和药物敏感性分离株中所占的比例分别为77.8%(42/54)和60.2%(213/354)。多元回归分析提示北京基因型与不同地区存在联系,但与耐多药无关。结论:北京基因型结核分枝杆菌在中国流行至少50年,并且与地区有关。     

Drug-resistant Mycobacterium tuberculosis in Korean isolates

Tuberculosis is a common disease in developing countries. An increasing incidence of resistance to isoniazid (INH) and streptomycin in organisms isolated from patients who contracted their disease in these countries, particularly in the Far East, is well recognized. This drug resistance has led to the recommendation of empirically beginning a regimen in patients with tuberculosis from the Far East of INH, ethambutol, and rifampin. This report documents the increasing incidence of resistance in isolates from Korea to ethambutol and rifampin in addition to INH and streptomycin. It suggests that the empiric use of INH, ethambutol, and rifampin in this group of patients could potentially lead to resistance to all of these drugs because of a significant amount of multidrug resistance. A regimen of INH, rifampin, pyrazinamide, and capreomycin is suggested as appropriate initial therapy in these patients based on the in vitro sensitivity data presented and initial clinical experience.     

Molecular epidemiology of Mycobacterium tuberculosis in China: a nationwide random survey in 2000.

OBJECTIVE: To determine the contribution of the Mycobacterium tuberculosis (TB) Beijing genotype to the population structure of M. tuberculosis complex in China. DESIGN: Genotypes of 441 mycobacterial isolates were determined by spoligotyping and IS6110 restriction fragment length polymorphism (RFLP). The isolates were from a nationwide random survey for the epidemiology of TB conducted in 2000, and the drug susceptibility patterns and epidemiological data were known. RESULT: A total of 408 samples contained M. tuberculosis as determined by spoligotyping. Of the M. tuberculosis strains, 64.9% (265/408) were of the Beijing genotype. Using the chi-squared test, no statistically significant differences were observed in the proportion of Beijing genotype TB in patients of different sex, age or living in different areas of the country, but a significant difference was observed with multidrug-resistant (MDR) TB: 77.8% (42/ 54) of MDR isolates were of the Beijing genotype vs. 60.2% (213/354) of the drug-susceptible isolates. In the multivariate logistic regression model, the Beijing genotype was significantly associated with region and not with MDR. CONCLUSION: The M. tuberculosis Beijing genotype has prevailed in China for at least five decades and is associated with region.     

Drug-resistant strains of Mycobacterium tuberculosis isolated in Russia.

SETTING: State Research Center for Applied Microbiology, Russian Research Institute of Phthisiopulmonology (Ministry of Health, Moscow). OBJECTIVE: To analyze drug-resistant clinical isolates of Mycobacterium tuberculosis obtained from patients referred to the institute from different parts of Russia, and to study the mechanisms of their rifampicin resistance. DESIGN: Fifty clinical isolates of M. tuberculosis were analysed. Polymerase chain reaction (PCR) and sequencing were used to study the mechanisms of rifampicin resistance in 25 isolates. RESULTS: Among cultures isolated from 50 patients, drug resistance was detected in 33. Most of the isolates were resistant to rifampicin (25 isolates), isoniazid (14 isolates), and streptomycin (seven isolates). Only 6% of the isolates were resistant to one drug, while 14% were resistant to two, 32% to three, 40% to four, and 8% to five drugs. Susceptible isolates were derived from 17 patients. The following point mutations and deletions in the rpoB locus, responsible for high level rifampicin resistance (more than 50 microg/ml in egg-based medium), were detected: G-->A/395 (Arg-->Gln), C-->T/232 (His-->Tyr), C-->T/221 (Ser-->Leu), G-->T/202 (Asp-->Tyr), GA-->TT/202-203 (Asp-->Phe), deltaATGGACCAG/199-207 (Met, Asp, Gin), A-->T/91 (Met-->Leu), TG-->CC/227-228 (Leu-->Ser), GAG-->AGT/349-350-351 (Gln-->Ser), deltaGGG/354(Gly). CONCLUSION: A number of previously unrecognised genetic modifications in the rpoB region were found in rifampicin-resistant strains isolated from patients from different parts of Russia.     

第四次全国结核病流行病学抽样调查--结核分支杆菌耐药性分析与评价

目的：分析我国结核分支杆菌耐药现状，为评价和指导国家结核病控制规划（NTP）提供基本数据，方法：对第四次全面流调的分离菌株进行6种抗结核药物（INH，SM，RFP，EMB，PAS－Na和TB1）的耐药性测定，结果：392株结核分支杆菌的总耐药率为27．8％，初始耐药率和获得性耐药率分别为18．6％和46．5％，耐多药率为10．7％，其中初始和获得性耐多药率分别为7．6％和17．1％；6种抗结核药物的耐药率由高到低分别为INH（17．6％），SM（17．3％），RFP（16．6％），PAS－Na(2.8%)，EMB（1．5％），和TB1（1．3％），耐1种，2种，3种和4种以上药物的初始耐药率和获得性耐药率分别为7．6％，4．6％，1．9％和14．7％，19．4％，10．1％和2．3％，不同性别，年龄组初始耐药差异无显著性。结论：本次流调的总耐药率，初始耐药率与第二次和第三次流调资料比较有显著性降低（P＜0．01），但仍处于较高水平，且耐药性的发生更趋向于这主要一线药物耐药和对多种药物耐药，尤其是MDR－TB发生率高，应引起重视。     

Drug-resistant tuberculosis in Yangon, Myanmar

The extent of drug resistant tuberculosis (TB) in the capital city of Myanmar, Yangon has not yet been reported. This study aimed to determine the proportion and pattern of drug resistance to first-line anti-TB drugs, among Mycobacterium tuberculosis complex isolates from sputum smear positive TB patients who attended National TB Programme Yangon centres in April-August and October-December 2002. Drug susceptibility was determined by the Mycobacteria Growth Indicator Tube manual system (Becton Dickinson, MD, USA). Of the 567 patients, sputum specimens from 447 (79%) had a positive culture. Of these, 357 isolates (80%) had a susceptibility test result. Isolates from 76 of 259 (29.3%) new patients and from 45 of 98 (45.9%) previously treated patients were resistant to at least 1 of the anti-TB drugs. Resistance to isoniazid (INH) (22.0% vs 40.8%: new vs previously treated patients) and to > or =2 drugs (17.8% vs 29.6%: new vs previously treated patients) was common. Multidrug- resistant TB (MDR-TB) among new and previously treated patients was 4.2% and 18.4%, respectively. INH-resistant (adjusted OR: 2.0, 95% CI 1.1-3.6) and MDR-TB (adjusted OR: 3.4, 95% CI 1.4-8.3) cases were more likely to have taken anti-TB drugs > or =1 month previously. Collectively, prevalence of MDR-TB and TB resistance to > or =2 drugs are not rare in Yangon.     

Drug-resistant tuberculosis in Poland in 2000: second national survey and comparison with the 1997 survey.

SETTING: Three years after the last survey of drug-resistant tuberculosis in Poland, a nationwide survey was conducted by the National Tuberculosis Reference Laboratory in cooperation with all TB laboratories. OBJECTIVE: To determine the prevalence and patterns of primary and acquired drug resistance among Mycobacterium tuberculosis isolates recovered from tuberculosis patients in Poland in 2000 and to compare the results with an earlier survey carried out in 1997. DESIGN: In a prospective survey based on the questionnaires and strains of M. tuberculosis from all 16 regional centres participating in the study, 3705 questionnaires and cultures were obtained from 3037 new and 668 previously treated patients excreting TB bacilli during the 12-month period of 2000. Tests of resistance to isoniazid, rifampicin, streptomycin and ethambutol were performed using L?wenstein-Jensen and the Bactec system. RESULTS AND CONCLUSION: Compared with the previous survey in 1997, the current survey showed a twofold increase in tuberculosis resistance in new cases: any resistance was 3.6% in 1997 vs. 6.1% in 2000 (P < 0.001), multidrug resistance was 0.6% vs. 1.2% (P < 0.01), and no cases of four-drug resistance in 1997 vs. 15 cases in 2000. No statistical differences were observed in the rate of acquired resistance in both surveys.     

The nationwide tuberculosis drug resistance survey in Mongolia, 1999.

SETTING: Mongolia, a country in the Western Pacific Region burdened with many cases of tuberculosis, with rapid expansion of DOTS over the last several years. OBJECTIVE: To determine the prevalence of resistance to major anti-tuberculosis drugs among tuberculosis patients who have never been treated previously. DESIGN: Sputum specimens were collected from all smear-positive tuberculosis patients identified from 1 November 1998 to 1 May 1999. RESULTS: Resistance to any of the four major drugs (streptomycin, isoniazid, rifampicin, and ethambutol) was as high as 28.9% (95%CI 24.7-33.5), primarily due to high streptomycin resistance of 24.2% (95%CI 20.3-28.6). Isoniazid resistance was also high, at 15.3% (95%CI 12.1-19.1). Resistance levels to ethambutol and rifampicin were relatively low, at 1.7% (95%CI 0.8-3.5) and 1.2% (95%CI 0.5-2.9), presumably because these drugs were only recently introduced into Mongolia. Multidrug resistance was also rare, at 1.0% (95%CI 0.1-1.8). Drug resistance rates were higher in middle-aged patients than in younger and older age groups combined (P = 0.006). Males tended to have higher resistance than females, although this was of statistically marginal significance (P = 0.08). No significant regional differences in drug resistance were found. CONCLUSION: While multidrug resistance was rare, isoniazid resistance was very common, which necessitates closer monitoring of the treatment outcomes of individual patients as well as long-term follow-up for drug resistance on a nationwide scale.