耐多药结核病耐药原因及用药

耐多药结核病（MDR-TB）指患者至少对异烟肼（INHH）和利福平（RFPR）两种以上药物产生耐药的结核患者。MDR-TB往往发生在经标准短化方案和复活方案反复治疗失败的患者。MDR—TB大多见于复治结核病患者,其耐药品种及具体情况不尽相同,故治疗方案必须相对个性化。     

多药耐药结核病治愈一例

近年来,由于流动人口增加、结核病（TB）控制措施薄弱和HIV/AIDS的流行使耐药结核,特别是多药耐药（multidrug resistance,MDR）-TB日益增加,其流行与传播已引起全球医学界的高度关注。MDR-TB具有传染性强、复发率高、病死率高、治疗费用昂贵、临床治疗困难等特点,给TB的防治带来困难,同时也成为当今研究热点和难点。本文报道1例MDR-TB治愈病例。     

耐多药结核病的流行和预防措施

耐药结核病的产生和流行日趋成为严重的公共卫生问题,是当前结核病控制工作面临的一个严重挑战。全球结核病耐药患者中,耐多药结核病（MDR-TB）患者所占比例较大、疫情较为严重,几乎全球各国均已出现耐多药病例。MDR-TB具有治疗时间长、治疗费用高、治疗效果差、传染性强等特点,因此也被认为是影响结核病监控和治疗的难题12j。MDR．TB是耐药结核的一种特定形式,指结核菌对至少2种最强有力的抗结核药物异烟肼（isoniazid,INH,H）和利福平（rifampiein,RFP,R）具有耐药性时,产生MDR—TB。MDR-TB既可是原发性,又可是获得性耐药。     

结核分枝杆菌耐药检测及其临床意义

耐药结核病(TB)尤其是耐多药结核病(MDR-TB)、广泛耐药结核病(XDR-TB)的快速诊断和有效治疗是TB防控中亟需解决的难题。结核分枝杆菌(Mtb)耐药的主要机制是由于药物作用靶标或药物代谢酶编码基因突变所致。临床上常用的Mtb药物敏感性试验方法主要包括表型药敏方法和分子药敏方法,本文还简要地概述了通过药敏试验所揭示的一些值得临床医师关注的临床意义。     

耐药肺结核患者耐药分析

我国目前约有耐药肺结核患者54万人，其中耐多药肺结核（MDR—TB）患者约20万人。耐药结核病、特别是耐多药结核病的增多对全球结核病控制造成了严重威胁。加强耐药性结核病的研究已刻不容缓。为了解肺结核患者耐药相关情况，进行调查，现报告如下：     

靶向结核耐药机制的抗结核药物增效剂的研究进展（英文）

结核病(Tuberculosis, TB)是一个全球性的健康问题,由于耐多药结核病(multidrug-resistant tuberculosis, MDR-TB)菌株的出现,抗结核药物出现防治困难。针对耐药机制开发抗结核药物的增效剂可以减少耐药性的出现和缩短治疗时间。本文从靶向细胞壁、外排泵和β-内酰胺酶的增效剂与抗结核药物的联合应用进行综述,为后续开发活性更好、毒性更小的新型增效剂提供参考。     

90例多种耐药肺结核耐药原因分析

多种耐药结核病(MDR-TB)患者用异烟肼、利福平等常规化疗药效果差,临床治疗很困难,痰菌不易阴转,传染期长,病死率高,治疗开支大。本文就1994年1月至1997年12月期间人住我院的90例MDR—TB耐药原因进行分析。 材料与方法 1、资料来源:我院1994年1月至1997年12月共收治肺结核病人660例,其     

结核分枝杆菌的耐药机制与治疗进展

目前结核病仍是威胁人类健康重要杀手。据世界卫生组织估计,目前全球约有20亿人感染结核分枝杆菌(结核菌),其中约有5000万人感染耐药结核菌。导致结核病发病率升高的重要原因就是耐药结核杆菌尤其是耐多药结核杆菌(MDR-TB)的出现和传播。我国不仅是全球结核病的第二大重灾区,也是WHO确定耐多药结核病的高发地区。因此对结核菌耐药机制的研究具有非常重要的意义。结核菌耐药性的产生主要是药物作用靶基因突变所致。结核病控制的最好方法即是治疗,目前化学药物仍是治疗耐药结核病的主要武器。本文就结核分枝杆菌的耐药机制及最新治疗进展做一介绍。     

耐多药及广泛耐药结核病的临床治疗策略

耐多药结核病(MDR-TB)和广泛耐药结核病(XDR-TB)通常被认为具有很高的死亡率,但如药物选择得当,联合治疗方案设计合理,其中的许多病例是能够治愈的.本文依据现有抗TB药物的疗效、安全性和治疗费用等分组(5组)探讨了它们在这些难治性TB推荐方案(由4种或以上对结核杆菌分离株可能敏感的药物组成)中的选用原则.其中,...     

结核分枝杆菌耐药性快速检测方法研究进展

由结核分枝杆菌（TB）引起的结核病是当今全球流行最广泛、最普遍的传染病之一。自上个世纪80年代以来，本已被控制的结核病发病率呈现上升的趋势，其主要原因是流动人口的大量增加，耐多药结核病（MDR—TB）的流行及HIV感染、器官移植、免疫抑制剂使用导致免疫力低下患增多，其中MDR—TB是结核病回潮的最主要原因。由于MDR-TB对多种抗结核药物耐药而导致治疗十分困难，该病传播迅速，病死率高。为从根本上控制该病的流行，实验室工作应使用快速、有效的新技术代替传统实验方法，及时为临床提供诊断和治疗依据，早期发现病情并使用敏感的抗结核药物。因此，快速、准确的耐药性检测试验成为近年来研究的热点和难点。本就快速检测TB耐药性方法的研究进展综述如下。     

儿童耐多药结核病发生的相关影响因素及其预测模型的建立

目的 探究儿童耐多药结核病（MDR-TB）发生的相关影响因素及其预测模型的建立。方法 回顾性选取2010年3月1日至2022年2月28日昆明市第三人民医院结核病病儿,统计MDR-TB发生情况,比较MDR-TB病儿与非MDR-TB病儿临床资料,通过logistic多因素回归模型分析儿童MDR-TB发生的相关影响因素,采用R语言构建儿童MDR-TB发生的列线图预测模型,并进行一致性检验。结果 共纳入850例结核病病儿,其中初治MDR-TB病儿占5.65%,复治MDR-TB病儿占24.88%,总MDR-TB病儿占10.47%;logistic多因素回归模型分析显示,年龄、吸烟史、治疗情况、感染播散性、与结核病病人接触、合并人类免疫缺陷病毒（HIV）感染、合并乙型肝炎病毒（HBV）感染是儿童MDR-TB发生的独立危险因素,规范用药是独立保护因素（P<0.05）;根据影响因素构建儿童MDR-TB发生的列线图预测模型,通过Bootstrap自抽样法验证显示该预测模型预测值与实际观测值基本一致,一致性指数（C-index）为0.960,具有良好的区分度;预测模型ROC曲线的曲线下面积（AUC）...     

Drug-resistant tuberculosis: an insurmountable epidemic?

Drug-resistant tuberculosis has brought back the spectre of pre-antibiotic days. WHO surveillance data from 2007 showed multi-drug-resistant tuberculosis (MDR-TB)—tubercle bacillus resistant to both isoniazid and rifampicin accounting for 4.8% of all new and subsequent cases of tuberculosis. India and China—the two most populated countries of the world, house the maximum number of drug-resistant tuberculosis cases. In eastern European and central Asian countries, more than 6% of new TB cases are MDR-TB, whereas the number is <3% in the countries of the western world. Extensively drug-resistant tuberculosis (XDR-TB) has emerged with the prospect of tuberculosis becoming an incurable disease. A surveillance spreading over the six continents showed 10% of MDR-TB cases were also XDR-TB. The fact that tuberculosis is the most common opportunistic infection among HIV-infected patients in developing countries makes the challenge almost insurmountable. The mortality of HIV and MDR-TB co-infected patients is exceedingly high. The absence of guidelines for treatment of drug-resistant tuberculosis and of infrastructure for delivery of DOT program and rapid laboratory diagnostic facilities, including drug susceptibility testing for both first and second-line drugs, and lack of trained human resource in most of the developing world account for the emergence and perpetuation of this menacing problem. WHO along with partnership with Green Light Committee and individual national governments has started DOT plus program to control this global epidemic.     

Targeting the human macrophage with combinations of drugs and inhibitors of Ca2+ and K+ transport to enhance the killing of intracellular multi-drug resistant Mycobacterium tuberculosis (MDR-TB)--a novel, patentable approach to limit the emergence of XDR-TB

The emergence of resistance in tuberculosis has become a serious problem for the control of this disease. For that reason, new therapeutic strategies that can be implemented in the clinical setting are urgently needed. The design of new compounds active against mycobacteria must take into account that tuberculosis is mainly an intracellular infection of the alveolar macrophage and therefore must maintain activity within the host cells. An alternative therapeutic approach will be described in this review, focusing on the activation of the phagocytic cell and the subsequent killing of the internalized bacteria. This approach explores the combined use of antibiotics and phenothiazines, or Ca(2+) and K(+) flux inhibitors, in the infected macrophage. Targeting the infected macrophage and not the internalized bacteria could overcome the problem of bacterial multi-drug resistance. This will potentially eliminate the appearance of new multi-drug resistant tuberculosis (MDR-TB) cases and subsequently prevent the emergence of extensively-drug resistant tuberculosis (XDR-TB). Patents resulting from this novel and innovative approach could be extremely valuable if they can be implemented in the clinical setting. Other patents will also be discussed such as the treatment of TB using immunomodulator compounds (for example: betaglycans).     

Treatment of multidrug-resistant and extensively drug-resistant tuberculosis: current status and future prospects

Drug resistance in Mycobacterium tuberculosis arises from the man-made selection of mutants that result from spontaneous chromosomal alterations. Preventing the development of drug-resistant TB through a good control program based on directly observed treatment, short-course, is of paramount importance. Established multidrug-resistant (MDR)-TB requires alternative specific chemotherapy, comprising drugs with higher cost and greater toxicity delivered on a programmatic basis. The development of new anti-TB drugs would help to prevent and treat MDR-TB. Notably, moxifloxacin and gatifloxacin are being tested for shortening treatment in Phase III trials, while three novel compounds, TMC-207, OPC-67683 and PA-824 are in Phase II studies for both drug-susceptible and drug-resistant disease. The roles of surgery and immunotherapy in the management of MDR-TB require further evaluation. The recent emergence of extensively drug-resistant TB poses a serious challenge to the global control of TB. In order to combat extensively drug-resistant TB, strengthening of directly observed treatment, short-course and drug-resistance programs, alongside other strategies, including the development of newer diagnostics and drugs, is mandatory.     

肺结核患者的MDR-TB知识知晓率调查

目的了解肺结核患者的MDR-TB知识知晓率情况,为有针对性开展健康教育工作提供参考。方法对肺科门诊跟踪治疗管理的肺结核患者进行询问式问卷调查。结果共调查159例肺结核患者,小学及以下学历占67.2%,"什么是MDR-TB"的知晓率为55.9%,"慢性排菌者/初治失败者/复发患者/密切接触MDR-TB患者的涂阳肺结核患者应怀疑得了MDR-TB"的知晓率为13.8%,"产生MDR-TB的原因"的知晓率为26.4%,"如何治疗MDR-TB"的知晓率为15.1%,"MDR-TB能治好吗"的知晓率为30.2%,"如何预防MDR-TB"的知晓率为23.9%。结论肺结核患者的MDR-TB知识知晓率低,应加强MDR-TB的宣传教育。     

还原型谷胱甘肽治疗耐多药结核病肝功损害的疗效观察

目的应用还原型谷胱甘肽治疗耐多药结核病肝功损害,并进行临床观察。方法静脉滴注还原型谷胱甘肽治疗耐多药结核病肝功损害36例(其中共选取病例72例,随机分成两组)与甘草酸二胺36例对照比较。结果还原型谷胱甘肽组患者肝功能指标改善明显优于对照组,两组比较差异有统计学意义(P<0.05)。结论还原型谷胱甘肽在治疗耐多药结核病肝功损害中对恢复肝功能指标疗效确切,安全性良好,可作为耐多药结核病肝功损害的一种有效药物。     

结核病免疫治疗进展

结核病是由结核分枝杆菌引起的一种慢性传染病。近年来,由于人类免疫缺陷病毒(HIV)感染的增加以及结核杆菌多重耐药菌株的出现,结核病的临床治疗面临新的挑战。免疫治疗通过改善细胞免疫功能而提高结核病的治疗效果,尤其是在免疫功能低下及耐多药结核的患者中显得尤为重要。本文综述了结核病免疫治疗近几年的研究进展。     

Opportunities and challenges of using five-membered ring compounds as promising antitubercular agents

Tuberculosis (TB), a chronic infectious disease, is one of the greatest risks to human beings and 10 million people were diagnosed with TB and 1.6 million died from this disease in 2017. In addition, with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the TB situation has become even worse, which has aggravated the mortality and spread of this disease. To overcome this problem, research into novel antituberculosis agents with enhanced activities against MDR-TB, reduced toxicity, and shortened duration of therapy is of great importance. Fortunately, many novel potential anti-TB drug candidates with five-membered rings, which are most likely to be effective against sensitive and resistant strains, have recently entered clinical trials. Different five-membered rings such as furans, pyranoses, thiazoles, pyrazolines, imidazoles, oxazolidinone, thiazolidins, isoxazoles, triazoles, oxadiazoles, thiadiazoles, and tetrazoles have been designed, prepared, and evaluated for their antimycobacterial activity against Mycobacterium tuberculosis. In this article, we highlight the recent advances made in the discovery of novel five-membered ring compounds and focus on their antitubercular activities, toxicity, structure–activity relationships, and mechanisms of action.     

抗痨凝胶介入治疗耐多药肺结核空洞的疗效分析

目的探讨经纤维支气管镜进行结核空洞注药治疗耐多药肺结核的临床疗效。方法在X线透视下经纤维支气管镜导管介入空洞注入抗痨凝胶,加全身化学治疗（化疗）治疗耐多药肺结核患者89例（治疗组）,并与单纯化疗的91例患者（对照组）进行对照研究。结果治疗组痰菌转阴率在治疗3个月、6个月、18个月后分别为62．92％、76．40％、88．76％,显著高于对照组的26．37％、42．86％及56．04％（两两比较,均P〈0．01）。治疗18个月后,治疗组病灶显效率（显著吸收率＋吸收率）为93．26％,空洞闭合率为41．57％,显著高于对照组的63．74％及15．38％（两两比较,均P〈0．01）。结论全身化疗加经纤维支气管镜导管介入空洞内局部注药治疗耐多药肺结核,疗效显著优于单纯全身化疗。     

肺炎克雷伯菌耐碳青霉烯类抗菌药的研究进展

肺炎克雷伯菌是一种常见的机会性致病菌,为医院内感染的重要病原菌之一。近年来,肺炎克雷伯菌的感染率及耐药率呈上升趋势,碳青霉烯类抗菌药是治疗该菌最有效的抗菌药物,但随着使用的增加,其耐药性也不断增加。本文就肺炎克雷伯菌对碳青霉烯类抗生素耐药的主要机制：产生碳青霉烯酶、青霉素结合蛋白对碳青霉烯类亲和力的下降、高产AmpC酶或ESBLs合并外膜蛋白缺失、生物被膜、主动外排系统等方面的研究进展作一综述。