获得性免疫缺陷综合征合并结核病患者对结核分枝杆菌二线药物耐药特征分析

目的了解获得性免疫缺陷综合征（AIDS）合并结核病（TB）患者感染结核分枝杆菌二线药物耐药特点。 方法选取2010年4月至2012年10月于北京大学地坛医院教学医院住院的艾滋病合并结核病患者标本,由中国疾病预防控制中心培养鉴定。进行4种一线药物（异烟肼、利福平、链霉素、乙胺丁醇）和4种二线药物（卷曲霉素、卡那霉素、氧氟沙星、乙硫异烟胺）药敏试验监测,并对所有菌株在gyrA、gyrB、rrs、tlya、eis和ethA基因位点进行DNA测序以检测基因多态性。 结果经培养鉴定共得到31株结核分枝杆菌,其中12株耐卷曲霉素,8株耐氧氟沙星,4株耐卡那霉素,5株耐乙硫异烟胺,耐药率分别为38.71%、25.81%、12.90%和16.13%。7株菌为耐多药菌株,1株菌为广泛耐药菌株,耐药率分别为22.58%和3.23%。耐药菌株最常见的突变位点是rrs₁₄₀₁,gyrA₉₄和gyrA₉₀。一线敏感菌株中氧氟沙星的耐药率显著低于一线耐药菌株（P = 0.012）。性别与结核分枝杆菌耐药差异无统计学意义（P = 0.533）,年龄> 40岁组的氧氟沙星耐药率低于其余两组（P = 0.043）。结核初治组与复治组患者二线耐药率、CD4水平差异无统计学意义（P = 0.333、0.307）。 结论AIDS合并TB患者存在二线抗结核药物原发耐药,其中卷曲霉素耐药率最高,其次是氧氟沙星。     

220例肺结核患者耐药菌谱分析

目的探讨肺结核患者在抗结核治疗中的相关耐药特点及耐药性变化情况。方法随机选取220例已经确诊的涂阳肺结核患者,其中120例为初治患者,100例为复治患者,采用离心集菌法收集菌种后进行培养,然后对这220例患者的菌株行药敏实验（抗结核药物包括异烟肼、乙胺丁醇、利福平和链霉素）,对所测结果进行比较分析,并统计耐药菌普的结果变化情况。结果 220例患者的菌株中,耐药的108例,总耐药率达49.1%,耐单药率达27.3%,耐多药率达10.0%,多耐药率为11.8%;在初治病例中,耐药的44例,耐药率为36.7%;在复治病例中,耐药的为64例,耐药率达到64.0%;经过对比发现,初治病例中多见单耐药,而耐多药和多耐药多存在于复治病例中,经x2检验,具有统计学意义（P〈0.05）。结论通过对肺结核患者的耐药菌谱分析,使医生更好的了解该病的特点,利于提高治愈率和减少耐药性的发生,其临床指导作用非常巨大。     

徐州地区2695例涂阳肺结核患者结核分枝杆菌耐药状况分析

目的了解徐州地区耐药结核的流行情况及其耐药谱,探讨耐药结核发生的影响因素。方法选择本院收治的涂阳肺结核患者作为研究对象,釆用统一设计的调查表获取患者的基本信息和相关流行病学资料;对研究对象的痰标本进行一线和二线抗结核药物敏感性试验,获取耐药性资料;数据录入Excel表格,采用SPSS 18.0软件进行统计分析。结果本地区总的耐药率为17.29%,耐多药[至少同时耐异烟肼(INH)和利福平(RFP)]率为5.60%,广泛耐药率为0.26%;复治患者的耐药率(37.26%)高于初治患者(13.56%),两者差异有统计学意义(χ2=140.35,P0.05);单一耐药的菌株中耐INH的耐药率最高,在多耐药(对至少两种一线抗结核药耐药,但不包括同时耐INH和RFP)组合中,以INH+SM(链霉素)的组合构成比最高;耐多药组合中,以INH+RFP的组合构成比最高;耐药结核病在不同性别患者中分布的差异无统计学意义,在不同年龄患者中分布具有统计学意义,以41~60岁年龄组耐药率最高。结论徐州地区结核病总耐药率虽然不高,但耐多药率较高,性别分布差异无统计学意义,年龄分布以41~60岁年龄段最多。     

浙江省耐利福平结核分枝杆菌rpoB基因突变研究

目的 了解浙江省耐利福平结核分枝杆菌rpoB基因突变特征.方法 利用传统药敏检测法和以PCR为基础的DNA测序对从浙江省立同德医院和浙江省中西医结合医院的188例结核病患者中分离的188株结核分枝杆菌进行耐药分析和rpoB基因突变分析,观察结核分枝杆菌利福平耐药决定区基因突变情况与临床耐药的关系.结果 188株临床分离株中有57株为耐药株(30.3％),其中单耐利福平18株(9.6％),单耐其他抗结核药物28株(14.9％)(异烟肼10株、链霉素12株和乙胺丁醇6株);耐2种或2种以上药物(包括异烟肼、链霉素和乙胺丁醇)的多耐药临床分离株11株(5.9％).29株耐利福平菌株中,27株(93.1％)存在rpoB基因突变,其中526位突变率为55.6％ (16/27),513位突变率为22.2％(5/27),531位突变率为14.8％ (4/27),529位突变率为7.4％ (2/27);28株耐其他抗结核药物分离株中,4株(14.3％)存在rpoB基因突变,突变位点分别位于526位(2株)和513位(2株).其余131株敏感菌株rpoB基因均无突变发生.结论 浙江省耐利福平结核分枝杆菌与rpoB基因突变有关,主要以526位与513位突变为主.     

288份分枝杆菌菌型鉴定及药敏试验结果监测分析

目的:通过分析石家庄市第五医院肺结核病人的分枝杆菌菌种鉴定及药敏试验结果,了解耐药情况,为临床治疗肺结核病人提供可靠的实验数据.方法:对2007～2010年就诊于我院的肺结核病人的1001份标本,用改良罗氏法培养,对288份分离培养阳性菌株进行菌型鉴定及药敏试验,试验结果进行统计分析.结果:①培养阳性率295/1001(29.5％),288例培养阳性标本,人型结核分枝杆菌263例,牛型分枝杆菌28例,乌型分支杆菌1例,其他非典型分枝杆菌3例.②耐药菌株98株,人型分支杆菌耐药比例低于牛型(30.4％Vs57.1％,P＜0.01).耐药率从高到底依次为:乙胺丁醇18.4％、链霉素15.3％、利福平14.2％、异烟肼12.2％、氧氟沙星9.0％、左氧氟沙星8.3％、力克肺疾6.9％、阿米卡星5.8％、利福布丁4.5％.③单耐药菌株20例(7.6％)多耐药菌株25例(8.7％),耐多药菌株22例(7.6％),广泛耐药结核菌株6例(2.1％).结论:结核分支杆菌对抗结核药耐药率高,临床应根据结核杆菌药敏试验的结果,合理使用抗结核药物,减少耐药菌株的发生.     

人类免疫缺陷病毒/结核分枝杆菌双重感染者结核分枝杆菌分离株一线药物耐药特征

目的分析人类免疫缺陷病毒(HIV)感染者的结核分枝杆菌(MTB)分离株对一线抗结核分枝杆菌药物的耐药特征,为临床治疗HIV/MTB双重感染提供参考依据。 方法选取上海市公共卫生临床中心2012年1月至2016年12月收治的HIV合并MTB感染者154例(实验组)和单纯结核分枝杆菌感染者357例(对照组),进行异烟肼(INH)、利福平(RFP)、乙胺丁醇(EMB)、链霉素(STR)4种一线药物耐药性检测,比较两组患者MTB的总耐药率和总耐多药率,初始及获得性耐药、耐多药率。 结果HIV/MTB双重感染组患者总耐药率(44.2%,68/154)、初始耐药率(42.2%,19/45)、初始耐多药率(13.3%,6/45)、STR总耐药率(31.8%,49/154)和初始耐药率(28.9%,13/45)显著高于单纯结核分枝杆菌感染组(33.9%、25.0%、3.8%、22.7%、11.4%)(P均<0.05)。INH、RFP、EMB耐药率与单纯结核分枝杆菌感染组差异无统计学意义(P均> 0.05)。单纯结核分枝杆菌感染组患者获得性耐药率(39.1%,88/225)和获得性耐多药率(19.1%,43/225)分别高于初始耐药率(25.0%,33/132)和初始耐多药率(3.8%,5/132)(χ²= 16.785、P < 0.001;χ²= 7.393、P = 0.004)。 结论HIV/MTB感染者分离的MTB对一线抗结核分枝杆菌药物耐药率和耐多药率高,其中STR耐药最为严重,提示临床治疗应重视HIV/MTB双重感染者的结核耐药问题,及时采取预防措施和制定个体化治疗方案。     

耐多药脊柱结核研究进展

我国是全球22个结核病高负担国家之一,也是全球27个耐药结核病高负担国家之一。耐多药结核病（multiple drug resistant tuberculosis,MDR-TB）是指结核分枝杆菌至少同时对异烟肼、利福平耐药的结核病。由于MDR-TB的明确诊断费用昂贵并且治疗效果不佳,属于结核病中的顽疾,已经成为影响我国结核病控制的主要障碍之一。骨关节结核是肺外结核的主要病灶之一,     

骨关节结核病灶中耐多药结核分枝杆菌对疗效的影响

目的回顾性探索骨关节结核病灶中耐多药结核分枝杆菌对骨关节结核病疗效的影响及其对策。方法1993至1999年,确诊为复治骨关节结核病250例,男143例,女107例;年龄2～72岁,平均25.44岁;病变在脊椎、髋、膝和其他小关节。穿刺或外科手术获得病灶中脓液、干酪样物或肉芽组织等为标本,以BACTECTB460检测仪进行结核菌培养和药敏试验,NAP试剂进行初级鉴定,NTM分离培养物进一步鉴定分枝杆菌菌种。结果250例标本中,分离培养阳性培养物48例。结核分枝杆菌46例,阳性率为18.4%。其中同时耐异烟肼(INH)、利福平(RFP)、链霉素(SM)和乙胺丁醇(EMB)中三种药的结核分枝杆菌4例,同时耐异烟肼、利福平、链霉素和乙胺丁醇11例,共15例(6%)。在15例中有8例此次手术后切口破溃形成窦道,依据药敏试验结果改变化疗方案治疗,并经前后2或3次再手术,7例治愈,1例因窦道继发感染而死亡。另2例为非结核分枝杆菌(NTM),1例鉴定为鸟胞内分枝杆菌复合群,另1例鉴定未有结果,但均为耐多药(INH、RFP、SM、EMB、KM、CS)的NTM,治疗效果差。结论骨关节结核病灶中发现耐多药结核分枝杆菌(6%)和非结核分枝杆菌的病例,疗效极差,此类病例的化疗方案应个体化,可能需要多次手术才能治愈。     

耐多药结核病病因探讨

耐多药结核病（muhiple drug resistant tuberculosis,MDRTB）是指结核分枝杆菌至少同时对异烟肼、利福平耐药的结核病[1].其治疗极其困难而且费用昂贵,为难治结核病,控制不利将严重影响社会的稳定和经济的持续发展,也必然成为我国结核病控制规划实施最大的障碍.     

GeneXpert MTB／RIF系统在肺结核诊断及利福平耐药检测中的应用价值

结核病实验室检查是为结核病的确诊提供病原学证据,也是确诊传染性肺结核尤其是耐多药结核病的重要依据,是结核病诊断、治疗和防治效果评价的技术关键。全国第五次结核病抽样调查资料显示,我国15岁以上人群活动性、涂阳和菌阳肺结核的患病率分别为459／10万、66／10万和119／10万,结核分枝杆菌耐多药率为6．8％[1]。     

Pulmonary resection for multi-drug resistant tuberculosis

OBJECTIVES: Mycobacterium tuberculosis continues to be a major cause of morbidity and mortality throughout the world. Complacency by the medical profession and by patients has caused a new strain of Mycobacterium tuberculosis to emerge that is highly resistant to current antibiotics. The possibility of a new worldwide epidemic of drug-resistant Mycobacterium tuberculosis is of concern. Optimal therapy for patients infected with multi-drug resistant tuberculosis often requires surgical intervention to eradicate the infection. We report on our experience with pulmonary resection for multi-drug resistant tuberculosis. METHODS: During a 17-year period, 172 patients underwent 180 pulmonary resections. All patients had multi-drug resistant tuberculosis and had a minimum of 3 months of medical therapy before surgery. Muscle flaps were frequently used to avoid residual space and bronchial stump problems. RESULTS: During the study period, 98 lobectomies and 82 pneumonectomies were performed. Eight patients underwent multiple procedures. Operative mortality was 3.3% (6/180). Three patients died of respiratory failure, 2 patients died of a cerebrovascular accident, and 1 patient had a myocardial infarction. Late mortality was 6.8% (11/166). Significant morbidity was 12% (20/166). One half (91) of the patients had positive sputum at the time of surgery. After the operation, the sputum remained positive in only 4 (2%) patients. Mean length of follow-up was 7.6 years (range 4-204 months). CONCLUSIONS: Surgery remains an important adjunct to medical therapy for the treatment of multi-drug resistant Mycobacterium tuberculosis. In the setting of localized disease, persistent sputum positivity, or patient intolerance of medical therapy, pulmonary resection should be undertaken. Pulmonary resection for multi-drug resistant tuberculosis can be performed with acceptable operative morbidity and mortality.     

Characteristics of patients with drug resistant and drug sensitive tuberculosis in East London between 1984 and 1992.

BACKGROUND--The aim of this study was to investigate retrospectively factors associated with drug resistant tuberculosis at the London Chest Hospital. METHODS--The microbiology results for patients with tuberculosis at the hospital for the period 1984-92 were reviewed, together with case notes and chest radiographs of all patients with drug resistant tuberculosis and of 101 patients with drug sensitive tuberculosis notified during the same period as a control group. RESULTS--Culture positive pulmonary tuberculosis occurred in 292 patients. Drug resistant strains were isolated from 20 patients (6.8%). Ten of the 292 (3.4%) had strains resistant to a single drug and nine (3.1%) had resistance to more than one first line drug. One patient had strains resistant to isoniazid and capreomycin. Strains resistant to more than one drug were all resistant to isoniazid and rifampicin. In five patients these strains were also resistant to pyrazinamide and in two they were resistant to streptomycin. Single drug resistant strains were resistant to isoniazid (nine patients) or streptomycin (one patient). Among the risk factors studied previous treatment for tuberculosis was the most significant association with drug resistant tuberculosis (7/9) for patients with resistance to more than one drug; 5/11 for single drug resistance compared with 6/101 patients in the drug sensitive group (odds ratio 22.8). Other risk factors were bilateral disease at presentation (odds ratio 8.5), and disease at a young age (odds ratio 1.03). CONCLUSIONS--Previous treatment for tuberculosis and bilateral disease at presentation were found to be more commonly associated with cases of drug resistant than with drug sensitive tuberculosis.     

HLA半相合骨髓移植后并发肺结核四例

目的 探讨HLA半相合骨髓移植后并发肺结核的诊断与治疗.方法 4例白血病患者,采用阿糖胞苷、环磷酰胺及直线加速器全身照射进行预处理,然后接受HLA半相合未去T淋巴细胞骨髓移植.移植后采用环孢素A、短程甲氨蝶呤、霉酚酸酯、抗CD25单克隆抗体和抗胸腺细胞球蛋白预防移植物抗宿主病.4例均获造血重建.4例分别于移植后150 d、120 d、47 d和43 d出现高热,伴轻度咳嗽,痰少,或干咳无痰;肺部CT检查,均有异常改变,但无特征性;结核菌素试验及结核菌素抗体试验均呈阴性反应;既往均无结核病史及接触史.例1经开胸肺活检病理诊断为增殖性肺结核,另3例抗结核治疗有效,确立肺结核诊断.采用利福平、链霉素、吡嗪酰胺及异烟肼抗痨治疗9～12个月.结果 4例患者经抗结核治疗,体温下降,肺部病灶明显缩小、吸收,除1例因急性移植物抗宿主病死亡外,其余3例患者均存活.治疗期间,维持原免疫抑制方案,1例血环孢素A浓度一度较低,增加CsA剂量后恢复至正常范围.结论 HLA半相合骨髓移植后并发的结核感染,其临床表现不典型,肺部CT表现无特征性,应注意与其它感染相鉴别,抗结核治疗有效.     

Clinical value of the measurement of Mycobacterium tuberculosis specific antibody in pulmonary tuberculosis.

BACKGROUND: A serological test that could help to diagnose tuberculosis, especially smear negative disease, would contribute to patient management. METHODS: Levels of antibody to distinct antigens of Mycobacterium tuberculosis were assessed for their value in the diagnosis and management of pulmonary tuberculosis. Serum was taken from 52 patients who were smear positive, from 27 patients who were smear negative but with evidence of active tuberculosis (sputum culture positive in 16, response to antituberculosis chemotherapy in 11), from 11 patients with old healed tuberculosis (pre-antibiotic era), and from 39 healthy subjects vaccinated with BCG. RESULTS: In smear positive tuberculosis an enzyme linked immunosorbent assay using a single 38 kDa antigen gave a diagnostic sensitivity of 80% with a 100% specificity. In smear negative pulmonary tuberculosis, however, combination of the 19 kDa antigen, lipoarabinomannan (ML 34 epitope), and hsp 65 (TB 78 epitope) was needed to achieve a sensitivity of 64% with a specificity of 95%. Recurrent and extensive radiographic disease with a poor prognosis was associated with high anti-38 kDa and low anti-14 kDa antibody levels in patients with active disease. Patients with less pulmonary cavitation had high anti-19 kDa titres. Bacteriological relapse during treatment was indicated by a rise in anti-14 kDa (TB68 epitope) antibodies. Four patients with non-tuberculous mycobacterial infection showed no anti-38 kDa antibody. CONCLUSION: Antigen or epitope specific serology may help in the diagnosis, assessment of prognosis, and monitoring of chemotherapy in patients with pulmonary tuberculosis.     

尿液中结核杆菌rspL基因突变与其耐药性关系的研究

目的 探讨尿液中结核菌的链霉素耐药性与其相关基因突变的关系。方法 采用PCR单链构像多态性(SSCP)方法检测47株尿液结核菌rspL基因的突变状态，同时与结核菌的链霉素药敏结果进行比较。结果 47株例尿液结核菌rspL基因均为阳性表达。28株耐药菌株中，19株(68％)有rspL基因点突变；19株敏感株则未发现有rspL基因畸变。结论 PCR-SSCP检测尿液结核菌rspL基因状态能快速并较准确地发现和确定该结核菌对链霉素的敏感性，对临床的抗结核治疗具有重要意义。     

The ligase chain reaction as a primary screening tool for the detection of culture positive tuberculosis

BACKGROUND: The ligase chain reaction Mycobacterium tuberculosis assay uses ligase chain reaction technology to detect tuberculous DNA sequences in clinical specimens. A study was undertaken to determine its sensitivity and specificity as a primary screening tool for the detection of culture positive tuberculosis. METHODS: The study was conducted on 2420 clinical specimens (sputum, bronchoalveolar lavage fluid, pleural fluid, urine) submitted for primary screening for Mycobacterium tuberculosis to a regional medical microbiology laboratory. Specimens were tested in parallel with smear, ligase chain reaction, and culture. RESULTS: Thirty nine patients had specimens testing positive by the ligase chain reaction assay. Thirty two patients had newly diagnosed tuberculosis, one had a tuberculosis relapse, three had tuberculosis (on antituberculous therapy when tested), and three had healed tuberculosis. In the newly diagnosed group specimens were smear positive in 21 cases (66%), ligase chain reaction positive in 30 cases (94%), and culture positive in 32 cases (100%). Using a positive culture to diagnose active tuberculosis, the ligase chain reaction assay had a sensitivity of 93.9%, a specificity of 99.8%, a positive predictive value of 83.8%, and a negative predictive value of 99.9%. CONCLUSIONS: This study is the largest clinical trial to date to report the efficacy of the ligase chain reaction as a primary screening tool to detect Mycobacterium tuberculosis infection. The authors conclude that ligase chain reaction is a useful primary screening test for tuberculosis, offering speed and discrimination in the early stages of diagnosis and complementing traditional smear and culture techniques.     

结核分枝杆菌快速培养和常规药敏试验在脊柱结核治疗中的应用

目的 探讨BACT/ALERT 3D系统快速培养和绝对浓度法药敏试验对指导脊柱结核个体化化疗的应用价值,分析研究脊柱结核耐药情况.方法 根据临床表现、影像学表现、病理检查,50例患者诊断为脊柱结核,并接受手术治疗.收集术中所取脓液、干酪样组织.低温避光保存,8 h内送检,常规处理后接种液体培养基,使用BACT/ALERT 3D系统进行分枝杆菌快速培养.培养阳性者接种PNB和TCH培养基进行菌种鉴定,并将细菌接种至含药改良罗氏培养基,按绝对浓度法进行11种常用一线和二线抗结核药物药敏试验.结果 50例标本培养阳性21例(42%),人型结核杆菌19例,牛型结核杆菌2例.结核杆菌培养和药敏试验平均耗时41 d(28～58 d).其中耐药11例(52.4%),异烟肼耐药4例(19.0%),利福平和乙胺丁醇各1例(4.8%),链霉素3例(14.3%),力克肺疾2例(9.5%),左氧氟沙星8例(38.1%).结论 结核分枝杆菌快速培养和常规药敏试验准确度高,费用低,可检测常用一线和二线药物的敏感性,适用于指导脊柱结核个体化化疗方案的制定.异烟肼、利福平、吡嗪酰胺、乙胺丁醇或(和)链霉素联合用药方案对多数初治脊柱结核患者有效.     

Pulmonary tuberculosis among political asylum seekers screened at Heathrow Airport, London, 1995-9

BACKGROUND: Over 50% of cases of tuberculosis (TB) in the UK occur in people born overseas, and new entrants to the country are screened for TB. A study was undertaken to determine the prevalence and disease characteristics of pulmonary TB in new entrants to the UK seeking political asylum. METHODS: A retrospective analysis of the results of screening 53 911 political asylum seekers arriving at Heathrow Airport between 1995 and 1999 was performed by studying Airport Health Control Unit records and hospital medical records. Outcome measures were chest radiograph abnormalities, sputum smear, culture, and drug resistance data for Mycobacterium tuberculosis. RESULTS: The overall prevalence of active TB in political asylum seekers was 241 per 100 000. There were large variations in prevalences of TB between asylum seekers from different regions, with low rates from the Middle East and high rates from the Indian subcontinent and sub-Saharan Africa. The frequency of drug resistance was high; 22.6% of culture positive cases were isoniazid resistant, 7.5% were multidrug resistant (resistant to both isoniazid and rifampicin), and 4% of cases diagnosed with active disease had multidrug resistant TB. CONCLUSIONS: The prevalence rate of TB in political asylum seekers entering the UK through Heathrow Airport is high and more M tuberculosis isolates from asylum seekers are drug resistant than in the UK population. Extrapolating these figures, it is estimated that 101 political asylum seekers with active pulmonary TB enter the UK every year, of whom about 25 would have smear positive disease.