耐多药结核病的治疗现状

自上世纪中叶以来 ,随着化学治疗的不断完善 ,90 %以上的肺结核病人获得了治愈。然而 ,由于化学药物的广泛应用、HIV感染及治疗的不规范等 ,耐药结核病 ,尤其是耐多药结核病 (MDR TB)的出现 ,对全球结核病控制构成了严重的威胁。据WHO统计 ,目前 ,全球已有 5 0 0 0万人感染了耐     

含氯苯吩嗪方案治疗耐多药结核病的疗效及评价

耐多药结核病的出现和耐多药结核菌广泛传播是当前我国控制结核病的一大挑战.也是临床治疗的一个难点.[第一段]     

耐多药结核病的预防

耐多药结核病（MDR—TB）是指至少同时对异烟肼和利福平产生耐药的结核分枝杆菌引起的结核病。由于这类患者同时耐至少两种最有效的抗结核病药物，不仅治疗困难，还有可能不可治愈而持续传播耐多药结核菌，增加原发性MDR—TB发病的可能性，造成严重的流行病学和公共卫生隐患。WHO估计全球每年有30万MDR—TB新病例，而我国2000年耐多药率已达10．7％，其中初始耐多药率为7．6％，获得性耐多药率为17．1％。近年来一些省市报道的耐多药率还远远超过该水平，辽宁省和河南省已分别居于西太区9个耐药监测国家和地区的第1和第2位，被WHO称为两个MDR—TB的“热点省”，我国的耐多药结核病问题已经引起了我国和世界范围的关注。紧抓“初治”这个根本环节，采取多种积极措施，预防耐多药结核病的产生，已经成为控制结核病及耐药结核病在我国流行的迫切任务之一。     

耐多药结核病的若干问题

20世纪90年代由于结核病疫情在全球范围出现回升局面，耐药结核病的传播和耐药结核病在艾滋病（AIDS）病人中多次爆发流行．导致WHO发出“全球结核病紧急状态”的警告。至今，耐药、耐多药结核病（MDR-TB）已遍及世界的任何角落，成为严重威胁人类健康和生存的最危险因素之一。我国2000年第四次全国结核病流行病学调查报告显示初始耐药率为18．6％，在6种主要的抗结核药物中，有60％的初始耐药病人对2种以上的抗结核药物耐药，10．2％的病人对4种以上抗结核药物耐药。其中耐多药占7．6％；而获得性耐药率高达46．5％。耐多药占17．1％【1_。2000年全球平均原发耐多药为1．O％．获得性耐多药9．3％_2]，不难看出当前我国耐多药结核病的发生率已明显高于全球水平。由于缺乏抗结核新药，耐药、耐多药结核病难以治愈，为此，不可避免地将引发较高的死亡率和过重的医疗负担，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现实的障碍。如不积极地采取控制的措施，还将影响全球结核病控制战略的实施。因此，对耐多药结核病全方位的研究成为最受关注的课题。     

耐多药结核病的治疗

近十多年来 ,全球耐药结核病呈增长趋势 ,尤其是耐多药结核病 (ｍｕｌｔｉｄｒｕｇ ｒｅｓｉｓｔａｎｔｔｕｂｅｒｃｕｌｏｓｉｓＭＤＲ ＴＢ)的明显增多 ,给治疗带来了极大的困难。加速攻克ＭＤＲ ＴＢ的治疗难关 ,现已成为 2 1世纪结核病控制领域中的核心问题。ＭＤＲ ＴＢ的定义关于ＭＤＲ ＴＢ的定义 ,国际上存在广义和狭义两种观点 ,前者指对所有抗结核药物中两种或两种以上产生耐药的结核病 ,后者是指至少对异烟肼(ＩＮＨ ,Ｈ)和利福平 (ＲＦＰ ,Ｒ)两种或两种以上产生耐药的结核病[1] 。国内已统一采纳ＷＨＯ采用的ＭＤＲ -ＴＢ的狭…     

耐多药结核病的综合治疗

耐多药结核病(MDR-TB)指结核菌至少同时耐异烟肼(INH)和利福平(RFP)。全世界约有三分之二的结核病患处于发生MDR-TB的危险之中，一些国家MDR-TB呈增加趋势；我国MDR-TB的流行也相当严重。MDR-TB的治疗已成为结核病控制工作中亟待解决的问题。在化学药物治疗(简称化疗)的基础上同时配合免疫治疗、萎陷疗法(collapse therapy)、介入治疗或外科手术等综合性治疗手段，日渐为结核防治界所关注。     

耐利福平作为筛选耐多药结核病指标的评估

目的探讨耐利福平作为耐多药结核病筛选指标的可行性。方法对结核分枝杆菌临床分离株采用美国BD公司BACTEC MGIT 960全自动快速分枝杆菌培养鉴定药敏仪进行药敏试验,并对数据进行分析。应用诊断性试验评价指标评价耐利福平作为耐多药结核病筛选指标的科学性。结果在621株结核分枝杆菌临床分离株中,177株对利福平菌耐药,其中172株至少同时对异烟肼耐药,结核分枝杆菌的耐多药率为27.7%。若以至少同时耐异烟肼和利福平作为诊断MDR-TB的参考标准,以耐利福平作为MDR-TB筛选指标的敏感性为100%、特异性为98.9%、准确度为99.2%、阳性预测值为97.2%、阴性预测值为100%、阳性似然比为34.4、阴性似然比为0。结论我市耐多药结核病发生率高;耐利福平可以作为耐多药结核病的初步筛选指标。     

耐多药结核病的治疗与预防

近十多年来 ,由于抗结核药物的不合理使用 ,耐多药结核病 (MDR- TB)增多 ,它是指至少同时对异烟肼和利福平耐药。多为获得性耐药 ,常见 INH、RFP复治方案治疗失败的病例 ,但有少数为原发性者。据 WHO估计全球有 5 0 0 0万人感染了耐药性结核菌 ,其中至少 2 / 3有可能发展成 MDR- TB的危险。 1994～ 1997年WHO/ IUATL D在 35个国家对抗结核药物耐药性监测的结果表明 ,有 1/ 3国家原发性耐多药结核病的发生率在 2 %以上(0 %～ 10 .8% ) ,获得性 MDR- TB发生率在 13% (0 %～ 5 4 % )。我国 2 0 0 0年全国结核病流行病学抽样调查…     

卷曲霉素与耐多药结核病治疗

1.耐多药结核病 (MDR- TB)的重要性WHO在总结世界各国实施 NTP的成功经验后指出 ,在实施 NTP的国家 ,复治病例虽有减少 ,仍占现患肺结核病的 10 %～ 2 0 % ;继发耐药率高达 2 0 % ;其中 MDR- TB在继发耐药中仍占 4 %～ 10 % ,因此 ,WHO首次提出 ,在实施 NTP已久 ,并取得成功经验的国家应将 MDR- TB的治疗提上日程。这一建议引起各国关注 ,我国的结核病专家也极为重视并展开讨论 ,耐多药结核病治疗研究课题组 1998年开始立题研究。提出的 MDR- TB治疗方案是 :3CDOTh Z/ x DOTh(临床肺科杂志 .2 0 0 1;3(3) :5 1)。当前耐多…     

哈尔滨市耐多药结核病流行病学调查

为了科学地掌握哈尔滨市的多耐药结核病 (MDR- TB)流行情况 ,特在全市流调中做了关于 MDR- TB的专项调查研究 ,现将其调查结果报告如下。资料来源和标准资料来源于 1997年 4～ 8月对全市 (七个区十二县 )采取分层整群等比例随机抽样方法 ,抽取 39个流调点进行调查。对所发现的活动性肺结核患者 ,均进行痰结核菌检查 ,菌阳患者一律做耐药性测定 ,并对耐药病例加以调查分析。方法步骤按《1990年全国结核病流行病学抽样调查细菌学检查细则》中所规定的 ,采取绝对浓度间接法 ,应用改良罗氏培养基测定 ,分离菌株 ,并做菌型鉴定 ,筛选出人型结…     

Newer diagnostics for tuberculosis and multi-drug resistant tuberculosis

PURPOSE OF REVIEW: This article will review some of the recent developments for the rapid diagnosis and detection of drug resistance in tuberculosis. RECENT FINDINGS: Tuberculosis remains one of the major causes of death from a single infectious agent worldwide. Of great concern for tuberculosis control is the emergence of drug resistance since there is no cure for some multidrug-resistant strains of M. tuberculosis, and there is concern that they may spread around the world, stressing the need for additional control measures such as new diagnostics and better drugs for treatment. Recent advances in molecular biology and a better understanding of the molecular basis of drug resistance have provided new tools for rapid tuberculosis diagnosis. Other non-conventional diagnostic approaches have also been proposed. Nucleic acid amplification techniques, both commercial and in-house, and non-molecular methods are being evaluated. The overall accuracy of most of these tests is promising and some of them can be easily implemented in clinical mycobacteriology laboratories. SUMMARY: New genotypic and phenotypic methods for rapid diagnosis and detection of drug resistance have been developed and tested both in M. tuberculosis strains as well as in clinical samples. Further controlled evaluations are necessary in high-endemic countries for their eventual implementation in the routine diagnostic systems.     

经纤支镜灌注治疗耐多药肺结核

目的 探讨经纤支镜灌注治疗耐多药肺结核的治疗价值。方法 将26例耐多药肺结核病患随机分为治疗组和对照组。治疗组强化期采用纤支镜灌注治疗加全身化疗，对照组只进行全身化疗。结果 强化期结束时，经纤支镜灌注治疗组症状明显改善92.86%，痰菌阴转率85.71%，病灶显吸收率78.58%，明显高于单纯化疗组58.33％、50％、33.33%（P＜0.01-0.05）。结论 经纤支镜灌注治疗耐多药肺结核疗效显，且无并发症及明显副反应，值得进一步推广使用。     

耐多药结核病患者管理模式的系统综述

目的 系统回顾国际上不同国家和地区耐多药结核病患者的管理模式,探讨适合我国的患者管理模式。 方法 全面搜索了PubMed、ProQuest、中国医院知识仓库（CHKD）和万方数据资源系统等数据库中发表于2000-2010年的文章,以及相关出版物、会议资料汇编等材料。共检索到文献1151篇,排除观点性文章、信件、新闻、社论、评论、文献目录、会议摘要等,对符合条件的14篇文献和3个出版物进行分析。 结果 目前各国采取的耐多药结核病患者管理模式主要有4种：以住院治疗为基础的管理模式,主要在美国、法国等经济发达国家实施,要求患者接受住院治疗（共3篇文献）;以门诊治疗为基础的管理模式,要求患者定期到门诊进行检查和领取药品（1篇文献）;以住院和门诊治疗相结合的管理模式,规定患者强化期或细菌学检查阴转前在医院接受治疗,尔后在门诊继续接受治疗（共4篇文献）;以社区关怀为基础的管理,为中低收入国家采取的主要方法,是以门诊治疗为基础管理模式的升级,更为强调结核病防治规划的覆盖（共6篇文献）。 结论 耐多药结核病患者管理模式的选择与当地的疫情、经济、结核病防治规划和医疗卫生体系的覆盖程度相关,我国应进一步完善住院治疗和社区关怀相结合的患者管理模式。     

基于文献分析的耐多药肺结核影像学研究进展

耐药结核病是由耐药结核分枝杆菌所引起的呼吸道传染病,严重威胁着人类健康,尤其是耐多药结核病(multidrug-resistant tuberculosis,MDR-TB)治疗效果差,因此,及时发现耐多药结核病可以使患者得到更好的管理和治疗.本文根据已发表的文献资料,于2019年10月搜索PubMed数据库,搜索关键字...     

耐多药结核病的分子机制研究进展

耐药结核病尤其耐多药结核病的发生和流行是当前结核病疫情回升的主要原因之一,成为结核病控制的重要障碍.本文从耐多药结核病的发展现状出发,归纳了各种耐单药结核病、耐多药结核病已有的分子机制研究,从耐多药结核病发病治疗现状、分子生物学、耐多药检测技术角度指出了目前国内外耐多药结核病已有的分子机制研究成果,在此基础上对耐多药结核病发病的分子机制规律的研究前景予以了展望.     

耐多药结核病的分子机制研究进展

耐药结核病尤其耐多药结核病的发生和流行是当前结核病疫情回升的主要原因之一,成为结核病控制的重要障碍.本文从耐多药结核病的发展现状出发,归纳了各种耐单药结核病、耐多药结核病已有的分子机制研究,从耐多药结核病发病治疗现状、分子生物学、耐多药检测技术角度指出了目前国内外耐多药结核病已有的分子机制研究成果,在此基础上对耐多药结核病发病的分子机制规律的研究前景予以了展望.     

Management of multi-drug resistant tuberculosis: practitioner's view point

Multi-Drug Resistant Tuberculosis (MDR-TB) is a growing hazard to human health world wide and threat to control of tuberculosis. Current estimates report the prevalence of primary and acquired MDR-TB in India as 3.4% and 25% respectively. MDR-TB is suspected if sputum is persistently +ve for AFB along with clinical and radiological deterioration after multiple courses of irregular or regular treatment including 4 months of WHO retreatmant regimens under direct observation . Diagnosis is confirmed by drug susceptibility testing from reliable and reputed laboratories under constant quality control. Reports of susceptibility should not be accepted uncritically. Treatment of MDR-TB should be at a specialized centre with standard microbiology laboratory facilities. Though treatment guidelines including standardized, empirical and individualized approaches have been laid down by the WHO but therapy should be tailored to the needs of the particular patient. Treatment of MDR-TB is difficult, complicated, much costlier, challenging and needs experience and skills. All measures should be taken to persuade and encourage patients not to stop treatment despite all its discomforts to prevent morbidity, mortality and transmission of MDR-TB. Current proposal of DOTS Plus by WHO highlights the comprehensive management strategy to control MDR-TB. MDR-TB is a man-made problem and its emergence can be prevented by prompt diagnosis and effective treatment of all TB cases. Adoption of directly observed treatment short course (DOTS) to prevent the resistant/multi-drug resistant strains and careful introduction of second line drugs to treat patients with MDR-TB are the top priorities for the proper control of MDR-TB.     

耐多药结核病的分子机制研究进展

耐药结核病尤其耐多药结核病的发生和流行是当前结核病疫情回升的主要原因之一,成为结核病控制的重要障碍.本文从耐多药结核病的发展现状出发,归纳了各种耐单药结核病、耐多药结核病已有的分子机制研究,从耐多药结核病发病治疗现状、分子生物学、耐多药检测技术角度指出了目前国内外耐多药结核病已有的分子机制研究成果,在此基础上对耐多药结核病发病的分子机制规律的研究前景予以了展望.     

Immunotherapy for MDR-TB (multi-drug resistant tuberculosis)--its feasibility]

MDR-TB is known to be man-made-disease. Inappropriate treatment of tuberculosis is responsible for the development of MDR-TB. MDR-TB is often accompanied with the immunosuppression of the host. Given that we are unable to develop another potent anti-TB drug in near future, immunotherapy directed at combating immunosuppression and enhancing the host's own immune response is an attractive approach to supplement conventional chemotherapy for MDR-TB. Patients with AIDS and patients with abnormalities of macrophage function have frequent problems with TB. This is suggesting that the host defenses involved in protection against mycobacteria include T-cell and monocyte/macrophage functions. That is cell-mediated immunity. Diverse cytokines are known to play an important role in anti-TB cell-mediated immunity, including IL-2, IL-12, IL-18 and IFN-gamma. Various animal experiments are indicating that administration of these cytokine (s) did recover the suppressed immunity and rescued the host from death by tuberculous infection. However, we have to keep it in mind that the results obtained from animal model of mycobacterial infection on the study of pathogenesis and immune responses in TB is not always applicable to the understanding of human TB. Clinical trial of inhalation therapy with IFN-gamma showed some improvement for drug-resistant TB. Cytokine treatment, however, often gave some deleterious side effects such as high fever, malaise, general edema and even the death of the host. Clinical trials with M. vaccae have been extensively conducted by UK group. The mechanisms underlying its possible therapeutic action remain to be clarified, but when administered at an appropriate dose, it has been shown to elicit a strong Th1 immune response. From the practical view point of immunotherapy for TB, surrogate markers of disease eradication and protective immunity are urgently required. Such markers would facilitate clinical trials by providing early evidence that test compounds or vaccines are effective. Even during the era when no potent chemotherapeutic agents were available, one third of the patients with TB survived the disease and enjoyed the entire lives. Then the question is what determines the alternative: survival or death following development of drug resistant TB. Is it host immune responsiveness or virulence of the microbe, or both? Clearly much more work seems required before we are able to find some definite means to conquer MDR-TB in human.