惠州市肺结核患者耐药谱分析

目的分析惠州市肺结核患者耐药谱,了解其耐药程度及耐药趋势。方法选择本所结核科2009年1月—2014年5月收治的肺结核患者1 810例,其中初治者1 020例(初治组),复治者790例(复治组)。对所有患者的菌株进行11种体外药敏试验,包括:异烟肼(INH,H)、链霉素(SM,S)、利福平(RFP,R)、乙胺丁醇(EMB,E)、卡那霉素(KM)、丁胺卡那(AM)、卷曲霉素(CM)、左氧氟沙星(LOF)、氧氟沙星(OFX)、对氨基水杨酸(PAS)、丙硫异烟胺(TH1321),并分析患者耐药谱。结果 1 810例肺结核患者分离菌株对一线抗结核药物耐药率为50.8%(920/1 020),对二线抗结核药物耐药率为20.3%(367/1 020)。初治组患者耐多药率〔7.2%(73/1 020)〕和7种二线抗结核药物耐药率〔20.2%(206/1 020)〕均低于复治组〔31.1%(246/790)、20.4%(161/790)〕(P0.05)。耐多药肺结核患者的耐药菌株对S、E的初始耐药率和获得耐药率较高,复敏率较低;对AM、CM、PAS、TH1321的初始耐药率和获得耐药率较低、复敏率较高;KM、LOF、OFX有较高的复治耐药率。结论惠州市肺结核患者对一线抗结核药物耐药率较高,需进一步加强对耐药肺结核的防控。复治肺结核患者耐药率仍处于较高水平,对耐药肺结核的临床治疗和管理应给以足够的重视。建议耐多药治疗方案中推广使用AM、CM、PAS、TH1321。实时监测耐多药肺结核患者的耐药谱,获取更新更全面的药敏资料,有助于合理制定个体化治疗方案,减少广泛耐药肺结核的产生。     

惠州市最新肺结核耐药监测结果及趋势分析

目的分析惠州市最新肺结核耐药监测结果及趋势,为进一步完善本地区肺结核防控对策提供依据。方法 2013年1月—2014年5月,对惠州市各县区涂阳培阳患者进行抽样调查,本研究共监测6个试点,共纳入肺结核患者638例。对患者进行痰菌分离培养,采用比例法进行一线药及二线药耐药性检测。结果本次抽样菌株总耐药率为45.1%,其中初治总耐药率为33.1%、复治总耐药率为60.8%。初治涂阳患者单一耐药率〔12.9%(82/638)〕低于复合耐药率〔32.3%(206/638)〕,总耐多药率低于复治涂阳患者(P0.05)。初、复治涂阳患者异烟肼(INH,H)+利福平(RFP,R)耐药率均为最高。单一任意耐药顺序为:H(194)R(131)链霉素(SM,S)(131)氧氟沙星(OFX)(84)乙胺丁醇(EMB,E)(33)左氧氟沙星(LOF)(32)卡那霉素(KM)(31)对氨基水杨酸(PAS)(15)卷曲霉素(CM)(14)丁胺卡那(AM)(10)丙硫异烟胺(TH1321)(8)。结论惠州市肺结核耐药情况复杂多样,耐多药肺结核有上升趋势,面临耐多药、广泛耐药肺结核的挑战,应重点关注H、R、S这3种一线抗结核药物的合理使用,以减少耐药菌株的产生和传播,降低耐药肺结核发生率。     

1996—2006年南京地区结核病耐药状况分析

目的了解南京地区近年来结核病耐药的发展趋势。方法对1996—2006年南京市胸科医院肺结核病例采用绝对浓度间接法进行了10种常用抗结核药物的敏感试验并对结果进行分析。结果各年每种抗结核药物的耐药率在一定范围内上下波动,但是耐多药率却是呈现逐步上升趋势,一线抗结核药物的耐药率明显高于二线抗结核药物的耐药率。结论耐多药的发展趋势对目前以INH和RFP为主要抗结核药物的治疗方案构成了巨大的威胁,尽快开发新的低毒高效的抗结核药物是解决目前抗结核治疗困境的当务之急。     

耐多药肺结核患者抗二线结核药的耐药分析

目的了解耐多药肺结核患者对二线抗结核药物的耐药情况。方法对我院住院的341例耐多药肺结核患者二线抗结核药物的耐药情况进行分析。结果 341例MDR-TB对左氧氟沙星、丙硫异烟胺、力克肺疾、对氨基水杨酸、丁胺卡那霉素、卷曲霉素的总耐药率依次为49.9%、26.4%、24.9%、23.4%、18.5%、15.8%。复治组对二线抗结核药物的耐多药率明显高于初治组,不合理治疗是形成MDR-TB或XDRTB的主要原因。结论耐多药肺结核患者对二线抗结核药物耐药情况严重,要引起重视。     

复治肺结核并糖尿病患者耐药率及与血糖水平的关系刁丽丽 河北大学附属医院 071000

目的 探讨复治肺结核并糖尿病患者耐药率及与血糖水平的关系。方法 按照是否合并糖尿病将2012年5月至2014年5月我院收治的210例复治肺结核患者分为实验组(复治肺结核合并糖尿病)75例和对照组(单纯复治肺结核)135例,比较2组患者的耐药情况,并将实验组患者按照不同血糖水平分为＜7.1组12例、7.1~14.0组49例和＞14.0组14例,比较不同血糖水平与耐药率之间的关系。结果 实验组患者多耐药率、耐多药率、广泛耐药率及总耐药率均明显高于对照组,抗结核药物敏感率明显低于对照组,有显著差异(P＜0.05)；7.1~14.0组患者多耐药率、耐多药率、广泛耐药率及总耐药率均略高于＜7.1组,耐单药率和抗结核药物敏感率均略低于＜7.1组,但2组间比较,差异无统计学意义(P＞0.05)；＞14.0组患者耐多药率和总耐药率均明显高于＜7.1组,抗结核药物敏感率明显低于＜7.1组,有显著差异(P＜0.05)；＞14.0组患者耐多药率明显高于7.1~14.0组,多耐药率明显低于7.1~14.0组,有显著差异(P＜0.05)。结论 复治肺结核患者合并糖尿病后耐药率明显升高,且血糖水平越高耐药率越高。     

老年肺结核患者临床及耐药特征分析

目的分析92例老年肺结核患者的临床资料及结核分枝杆菌耐药特征。方法对2012~2014年遵义医学院附属医院收治的痰结核分枝杆菌培养阳性的92例老年肺结核患者的临床资料、一线和二线13种抗结核药的药物敏感试验结果进行回顾性分析。结果 92例老年肺结核患者中初治多于复治(2.6∶1),肺结核并结核性胸膜炎及基础疾病发生率高;结核分枝杆菌对13种抗结核药全敏感者43例,不同程度耐药者49例,总耐药率、初治耐药率和复治耐药率分别为53.3%(49/92)、48.5%(32/66)和65.4%(17/26);总耐多药率、初治耐多药率和复治耐多药率分别是12.0%(11/92)、4.5%(3/66)和30.8%(8/26);广泛耐药占耐多药的比率18.2%(2/11)。结论本地区年结核病疫情严峻,提高对老年肺结核的认识,重视病原学检测和规范化治疗,是防止误诊误治和减少耐药结核病发生的重要手段。     

1996—2006年南京地区结核病耐药状况分析

目的　了解南京地区近年来结核病耐药的发展趋势。方法 对1996—2006年南京市胸科医院肺结核病例采用绝对浓度间接法进行了10种常用抗结核药物的敏感试验并对结果进行分析。结果 各年每种抗结核药物的耐药率在一定范围内上下波动,但是耐多药率却是呈现逐步上升趋势,一线抗结核药物的耐药率明显高于二线抗结核药物的耐药率。结论 耐多药的发展趋势对目前以INH和RFP为主要抗结核药物的治疗方案构成了巨大的威胁,尽快开发新的低毒高效的抗结核药物是解决目前抗结核治疗困境的当务之急。     

165例耐药肺结核原因分析

本文收集江西省胸科医院2003年度住院肺结核病人耐药情况,对165例耐药肺结核原因进行回顾性分析。1对象和方法选2003年度1月~12月住院治疗的耐药肺结核病人。方法查阅2003年度痰抗酸杆菌培养阳性的病历资料,对其中耐药的病例进行分析。药物敏感性测定,采用改良罗氏培养基,绝对浓度法。耐药标准按中国防痨协会1995制定的结核病诊断和细菌学检验规程的标准。药敏检测H(异烟肼)、S(链霉素)、R(利福平)、E(乙胺丁醇)、P(对氨基水杨酸钠)五种基本抗结核药物的敏感性。耐药肺结核指耐一种或一种以上抗结核药物的肺结核病人;耐多药肺结核病指至少…     

荷兰不同来源耐多药结核病例中二线耐药情况

背景：荷兰。 目的：调查不同地理来源的耐多药结核病人耐二线药情况及其相关因素。 方法：对荷兰1993年1月至2007年10月间耐多药结核病人分离菌株的实验室数据进行回顾性研究。 结果：发现的153例耐多药结核病人中,18例（12％）为荷兰本国人。对其中的131例进行二线药物敏感性实验,有28例（21％）为耐二线药,且大部分为单一耐药（24／28（86％））;9例耐丙硫异烟胺（PTH）,6例耐对氨基水杨酸,4例耐阿米卡星（ASK）,4例耐环丙沙星,1例耐环丝氨酸）。有4例耐多药结核病人耐多种二线药;2例为广泛耐药的牛型结核分枝杆菌。在所有耐多药结核病人中,来自欧洲和中亚者二线耐药较普遍,且涉及的药物也较广泛。来自非洲和美洲者主要耐PTH,而来自东南亚者主要耐AMK。 结论：在荷兰,耐多药结核病人中二线耐药情况并不普遍。大部分二线耐药发生在移民当中,来源于不同的地域,病人耐药情况也不同。     

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。     

Resistance to anti-tuberculosis drugs among smear-positive cases in Thai prisons 2 years after the implementation of the DOTS strategy.

SETTING: Three prisons in Bangkok and vicinity, Thailand. OBJECTIVE: To examine the prevalence of drug-resistant tuberculosis among smear-positive cases in Thai prisons 2 years after the implementation of the DOTS strategy, and to identify factors associated with resistance to anti-tuberculosis drugs. METHODS: In a cross-sectional study, 154 consecutive tuberculosis patients with at least one positive sputum smear and at least one positive sputum culture registered between 1 May and 31 October 2000 were enrolled. Drug susceptibility testing was performed by the Ministry of Public Health Tuberculosis Division. Patient characteristics were obtained by face-to-face interview. RESULTS: Resistance to at least one drug was found in 50.6% of the subjects, including multidrug-resistant tuberculosis (MDR-TB) in 19.5%. The proportion of resistance to any anti-tuberculosis drug in prisons A, B and C was respectively 52.7%, 37.8% and 61.5%. The only factor significantly associated with resistance to at least one drug (P = 0.011) and MDR-TB (P < 0.001) was a history of previous tuberculosis treatment. CONCLUSION: After 2 years of the DOTS strategy, resistance to anti-tuberculosis drugs, an indicator of the quality of tuberculosis treatment, was found to be high. The DOTS strategy currently used in Thai prisons should be reviewed, in order to reduce and prevent drug-resistant tuberculosis.     

南京地区结核分枝杆菌耐药监测疫情趋势分析

目的了解南京地区胸科医院结核病患者结核分枝杆菌对临床常用9种药物的耐药情况。方法对我院分离的结核分枝杆菌采用绝对浓度法对9种抗结核药物:链霉素、异烟肼、乙胺丁醇、利福平、对氨基水杨酸、丁胺卡那霉素、卷曲霉素、左氧氟沙星、对氨基水杨酸异烟肼进行药敏试验,同时用PNB、TCH进行菌种初步鉴定。结果 10014株结核分枝杆菌中,总耐药率38.42%(3847/10014),单耐药率最高为利福平(27.35%),最低为卷曲霉素(0.50%);2017株耐多药结核分枝杆菌对另外7种药物单耐药率最高为链霉素(56.22%),最低为卷曲霉素(1.69%),对9种药物全耐者有3株。结论结核分枝杆菌对多种药物耐药率高,应加强抗结核药物耐药性监测,根据药敏试验结果选择科学有效的化疗方案。     

结核分枝杆菌吡嗪酰胺耐药相关基因研究进展

吡嗪酰胺是治疗结核病的重要抗结核药物之一,特别是用于耐多药结核病的治疗。近年来结核分枝杆菌对吡嗪酰胺的耐药逐渐增多,其耐药机制尚未明确。本文针对结核分枝杆菌吡嗪酰胺耐药及其与基因变异之间的关系研究进展进行综述,以供研究者参考。     

Determinants of drug-resistant tuberculosis: analysis of 11 countries.

SETTING: Eleven countries/territories. OBJECTIVES: Global information on the determinants of drug-resistant tuberculosis (TB) based on representative data is not available. We therefore studied the relationship between demographic characteristics, prior TB treatment, and human immunodeficiency virus (HIV) infection with anti-tuberculosis drug resistance. METHODS: Population-based representative data on new and previously treated patients with TB collected within an international drug resistance surveillance network. RESULTS: Of 9,615 patients, 8,222 (85.5%) were new cases of TB and 1,393 (14.5%) were previously treated cases. Compared with new cases, previously treated cases were significantly more likely to have resistance to one (OR = 2.5,95% CI 2.1-3.0; P < 0.001), two (OR = 4.6, 95%CI 3.7-5.6; P < 0.001), three (OR = 11.5, 95%CI 8.6-15.3; P < 0.001), and four (OR = 18.5, 95% CI 12.0-28.5; P < 0.001) drugs. An approximately linear increase in the likelihood of having multidrug-resistant tuberculosis (MDR-TB) was observed as the total time (measured in months) of prior anti-tuberculosis treatment increased (P < 0.001, chi2 for trend). In multivariate analysis, prior TB treatment for 6-11 months (OR = 7.6, 95% CI 2.6, 22.4; P < 0.001) and > or = 12 months (OR 13.7, 95% CI 4.5-41.6; P < 0.001), but not HIV positivity, was associated with MDR-TB. CONCLUSION: This study shows that prior but ineffective treatment is a strong predictor of drug resistance, and that HIV is not an independent risk factor for MDR-TB. The association between length of treatment and drug resistance may reflect longer treatment as a result of treatment failure in patients with drug resistance; it may also reflect irregular prior treatment for TB, leading to drug resistance.     

High prevalence of drug-resistant tuberculosis, Republic of Lithuania, 2002.

BACKGROUND: Nations of the former Soviet Union have the world's highest reported levels of resistance to anti-tuberculosis drugs. We conducted the first national survey of anti-tuberculosis drug resistance in the Republic of Lithuania. METHODS: We tested Mycobacterium tuberculosis isolates from all incident culture-positive pulmonary TB patients registered in 2002. New patients were those treated for <1 month with any first-line anti-tuberculosis drug (isoniazid [INH], rifampin [RMP], ethambutol, or streptomycin); previously treated patients were those treated for > or =1 month. RESULTS: Of 1163 isolates, 475 (41%) were resistant to at least one first-line drug, and 263 (23%) were resistant to at least INH and RMP (MDR); this included 76/818 (9.3%) from new patients and 187/345 (54%) from previously treated patients. Of 52 MDR isolates randomly selected for extended testing at an international reference laboratory, 27 (51%, 95%CI 38-66) had resistance to pyrazinamide, 21 (40%, 95%CI 27-55) to kanamycin, and 9 (17%, 95%CI 8-30) to ofloxacin. CONCLUSIONS: The prevalence of MDR-TB in Lithuania is among the world's highest. Among MDR-TB isolates, aminoglycoside and fluoroquinolone resistance were common. To combat drug-resistant TB, Lithuania has implemented the WHO global TB control strategy (DOTS), and is developing an MDR-TB treatment program (DOTS-Plus).     

Pretomanid(PA-824)治疗耐多药结核病的应用建议

耐多药结核病治疗疗程长达18~24个月、药物不良反应重、患者治疗依从性差,部分患者因耐药谱广泛,不能选择二线抗结核药物组成有效的治疗方案,导致死亡率高。因此,耐多药结核病治疗新药的研究是全球结核病控制的重要问题,也是我国改变耐多药结核病防治现状亟待解决的问题。全球结核病药物研发联盟研发的pretomanid(PA-824)与贝达喹啉和利奈唑胺组成的BPaL方案,针对严重耐多药结核病的治疗,具有疗程短、全程口服、治疗依从性高、治愈率高等优势,为严重耐多药结核病患者的治疗带来了新的希望。该方案于2020年被世界卫生组织在全球推荐使用。目前,贝达喹啉和利奈唑胺两种药品已经在我国上市,并作为二线抗结核药物用于耐多药结核病治疗。因此,亟待PA-824能早日在我国获批使用,以挽救更多耐多药结核病患者的生命。为此,中国防痨协会联合中国疾病预防控制中心结核病预防控制中心组织全国结核病防治、临床和基础研究等领域的专家,经反复讨论撰写了《Pretomanid(PA-824)治疗耐多药结核病的应用建议》,以期为加快PA-824及BPaL方案在我国的注册使用提供参考。     

Drug resistance trends among previously treated tuberculosis patients in a national registry in Peru, 1994-2001.

SETTING: National mycobacteriology reference laboratory in Peru conducting routine testing of susceptibility to isoniazid, rifampin, ethambutol, pyrazinamide, and streptomycin, in Mycobacterium tuberculosis isolates from previously treated patients. OBJECTIVE: To determine the percentage of isolates resistant to each of five anti-tuberculosis agents and to ascertain in these data the presence of trends of clinical relevance. DESIGN: Retrospective study of a national registry of M. tuberculosis isolates from patients referred for drug susceptibility testing between 1994 and 2001. RESULTS: Among 14,736 isolates tested, 10,837 (73.5%, 95%CI 72.8-74.3) demonstrated anti-tuberculosis resistance, and 8455 (57.4%, 95%CI 56.6-58.2) demonstrated resistance to at least both isoniazid and rifampin, by convention defined as multidrug-resistant tuberculosis (MDR-TB). A significant increasing trend could be discerned for resistance to each of the drugs tested and in isolates classified as MDR-TB (P < 0.001 for trend). Additional clinically relevant trends were found in polyresistance and multidrug resistance percentages. CONCLUSIONS: Data from a national reference laboratory can be used to inform the design of retreatment regimens.     

黄石市结核病耐药性监测研究报告

目的　按照WHO IUATLD《结核病药物耐药性监测指南》结核病耐药监测技术系统 ,掌握黄石市初始和获得性耐药水平 ,评价结核病控制效果。方法 黄石市1999年新发现涂阳病例为本次研究对象。并对全部培养阳性菌株用比例法作H、R、E、S四种药物药敏试验。结果 共入选 2 10例 ,其中培养阳性 2 0 0例,培养阴性 8例 ,污染 2例。总耐药率 18.5 % ,初始耐药率 12 .5 % ,初始MDR -TB率 4 .4 % ;获得性耐药率 4 2 .5 %,获得性MDR TB率 2 0 .0 %。结论 黄石市结核病耐药流行状况处于国内外监测结果低水平。初步建立了WHO IUATLD结核病耐药性监测系统,获得了黄石市耐药水平资料 ,对评价现行结核病控制策略效果 ,改进防治措施具有重要的必要性和指导性。     

四川地区346例耐药肺结核患者临床特征分析

目的了解四川地区346例耐多药(MDR-TB)和泛耐药(XDR-TB)肺结核患者的临床特征以及可能与耐药发生有关的因素。方法回顾分析成都市公共卫生临床医疗中心2016年1月~2017年6月收治的346例耐药肺结核患者以及2370例药物敏感肺结核患者的临床资料,通过比较分析二组的差异,探讨耐药肺结核患者的患病特点以及可能影响耐药发生的因素。结果耐药肺结核发病人群以男性为主,占70.52%(244/346),且各年龄组男性均多于女性;青壮年居多,占81.79%(283/346),老年和18岁以下患者占比分别为13.58%(47/346)和4.62%(16/346)。性别和年龄分布情况与药物敏感肺结核无明显差异。耐药患者中少数民族患者占比接近五分之一;初、复治病例分别占23.70%(82/346)和76.30%(264/346)。在86例使用过喹诺酮类药物的耐药患者中73.26%(63/86)的病例对此类药物耐药。主要临床症状与药物敏感肺结核患者无明显差异。耐药患者中并发肺组织外结核者占65.32%(226/346),与药物敏感肺结核组(72.57%,1720/2370)相比无明显差异。耐药患者胸部影像改变中,空洞、支气管扩张和肺叶毁损分别占75.72%(262/346),23.12%(80/346)和19.08%(66/346),均高于药物敏感肺结核组;病变累及范围分布与药物敏感肺结核组无差别。主要合并症中,合并HIV感染者18例,糖尿病53例,慢性肺部疾患者17例,与药物敏感组相比无明显差异。耐药结核分枝杆菌检出标本最常见者为痰液(82.08%,284/346)和支气管肺泡灌洗液(28.90%,100/346),其他多种组织均有检出。通过Xpert MTB/RIF检测方法,检出利福平突变阳性者82.56%(142/172);北京博奥晶芯分枝杆菌+耐药检测方法检出利福平耐药者90.65%(97/107)。结论耐药结核病在各年龄段人群均可发生,男性高于女性。主要表现与药物敏感肺结核患者无明显差异。复治患者是耐药结核病发病的高危人群,但初始耐药不少见。喹诺酮类药物的不规范使用可能与继发耐药有关。耐药患者肺外结核发生率与药物敏感肺结核患者无明显差异。其肺部影像改变较之药物敏感肺结核患者有更多的空洞、支气管扩张和肺叶毁损。快速分子生物学方法阳性率高,快捷有效。     

Rifampicin mono-resistant Mycobacterium tuberculosis in Bujumbura, Burundi: results of a drug resistance survey.

SETTING: Bujumbura, Burundi. OBJECTIVES: To determine resistance levels of Mycobacterium tuberculosis (TB) to the main anti-tuberculosis drugs after 11 years of a DOTS programme using a WHO-recommended partially intermittent 6-month rifampicin (RMP) first-line regimen and fixed-dose drug combinations (FDCs). DESIGN: Drug susceptibility testing of systematic samples of M. tuberculosis isolated from newly registered sputum smear-positive cases in the capital during a 15-month period (2002-2003). RESULTS: Of 496 strains from new cases, 16.1% showed resistance to any drug, 6.3% to isoniazid (INH), 2.0% to RMP (1.4% multidrug-resistant TB [MDR-TB]), 13.3% to streptomycin and 1.6% to ethambutol. Among 69 strains from previously treated cases, the prevalence of resistance was 30%, 19%, 15% (12% MDR-TB strains), 25% and 6%, respectively. CONCLUSION: Levels of drug resistance in Bujumbura are higher than average for Africa, despite long-term use of the DOTS strategy with FDCs and a ban on sales of TB drugs. Most worrying is the appearance of MDR-TB and RMP-resistant, INH-susceptible strains in new cases. Although a survey cannot prove that high HIV prevalence, elevated levels of resistance to some other drugs and irregular intake allowed acquisition of drug resistance, the effectiveness and safety of 6-month regimens with (partially) intermittent RMP throughout under such conditions should be investigated.