抗结核病新药作用分子机制研究进展

结核菌耐药现象越来越严重,开发治疗结核病的新药非常紧迫。全球药物研发的一个明显趋势是整合分子生物学及功能基因组方法学,结核病治疗药物的研发也如此。本文综述结核病新药分子靶标的鉴定、分子作用机理与耐药机理以及几种前景较好抗结核新药的药物学特征,并重点概括其应用及研究的最新成果。这将有助于结核病新药研发。     

抗结核药物的临床应用及不良反应

结核病是由结核分枝杆菌引起的慢性传染病,可侵及许多脏器、以肺部受累形成肺结核最为常见。目前在全球范围内由于耐药结核菌的产生与扩展,结核菌与人体免疫缺陷病毒(HRV)的双重感染以及许多国家结核病控制规则不完善,使全球结核病菌呈明显上升趋势。抗结核化学药物治疗对控制结核病起决定性作用,合理化疗可使病灶内细菌消灭最终达到痊愈。但抗结核药物存在许多不良反应,可造成严重后果.甚至危及生命,因此正确对待抗结核药物的作用及不良反应,有利于提高药物疗效的临床治愈率。     

肺结核治疗有门道

一、抗结核药物的研究发展 由于对结核菌耐药是导致结核病化疗失败的主要原因,因此研究新药已成为控制结核病的当务之急,现陆续开发并应用于临床的主要药物有利福霉素类、氟喹诺酮类、氨基糖甙类、大环内酯类、β-内酰胺类等.     

肺结核短程化疗的疗效和副反应

结核病化疗的一个重大突破是短程化疗,是当前各国结核病防治工作中受到重视的课题。有人把短程化疗称为八十年代结核病化学疗法的一次大变革。现将短程化学治疗药物作用机理、疗效、副反应综合介绍如下. 短程化疗药物作用机理继异烟肼以后,高效药物利福平的出现为短程化疗创造了条件。七十年代以来,对抗结核药物的作用机理以及结核菌在人体内的代谢状态有了进一步的了解,如高效抗结核药物不仅能杀死正在繁殖的结核菌     

初复治肺结核耐药203例分析

结核病依旧是 2 1世纪严重危及人类健康的疾病 ,耐药结核病是 2 1世纪全球结核病控制面临的重大课题之一。结核分支杆菌耐药性问题已引起世界范围的广泛重视 ,并将其作为制定结核病防治对策的重要依据 ,为此现将我院近年来收治的有结核菌药敏测定的初复治患者耐药情况做一研究 ,为初复治患者制定化疗方案经验选药提供依据。1　资料与方法1.1　一般资料资料来源于 1992— 1997年间我院收治的初复治肺结核有结核菌药敏测定的 2 0 3例患者 ,报告其对异烟肼、利福平、乙胺丁醇、对氨基水杨酸钠、链霉素、卡那霉素六种抗结核药物的耐药情况 ,其中…     

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。     

氟喹诺酮类药物的抗结核作用

结核病化疗的出现使结核病治疗发生了划时代的改变。据估计［１］,目前全球约有２０亿人感染了结核分支杆菌,每年有８００万新患者出现,３００万人死于结核病,约５０００万人携带结核分支杆菌耐药菌株。结核菌耐药已成为当今结核病控制所面临的一大难题,迫切需要抗结核新药的出现。氟喹诺酮类药物抗结核分支杆菌的作用引入瞩目,成为新药开发研究中的一个主要方向,其中环丙沙星、氧氟沙星、左氧氟沙星、司帕沙星已用于临床结核治疗,现综述如下。ｌ　作用机制　　　　氟喹诺酮类药物主要作用于细菌的脱氧核糖核酸（ＤＮＡ）旋转酶（拓…     

基因芯片与液体快速培养技术诊断耐药结核病的对比研究

目的 对比研究基因芯片与液体快速培养技术诊断耐药结核病的效果。方法 1156例疑似肺结核及肺结核患者的同一痰样本,同时应用基因芯片技术(芯片组)与液体快速培养技术(快培组)进行结核菌耐药检测,对两组检测结果进行对比分析。结果 对两组实验检测结果进行对比分析,结核菌检出率:芯片组270例,阳性率为23.36%,快培组237例,阳性率为20.50%。结核菌耐药结果 :芯片组46例,耐药率为17.04%,快培组43例,耐药率为18.14%,比较差异无统计学意义(P>0.05)。芯片组与快培组同时检出结核菌阳性时,二者耐药符合率达80%。结论 基因芯片检测结合聚合酶链式反应(PCR)技术和反向杂交技术(RDB)诊断结核病及耐药结核病,具有简便、快速、灵敏、准确的特点,及时检出结核病及耐药结核病,指导临床针对性制定个性化抗结核方案,避免盲目制定抗结核方案而导致医源性耐药结核病的出现,真正有效控制结核病及耐药结核病。     

抗结核病化疗药物研究的新进展

结核病是由结核分枝杆菌感染引起的,是全球重大人类传染病之一。现有用于抗结核病的化疗药物,品种少、选择余地小、治疗疗程长且不良反应严重。多药耐药和广药耐药结核分枝杆菌的出现使全球抗结核的形势日益严峻,开发疗效好、不良反应小且不易耐药的新型抗结核药物迫在眉睫。近10年来,抗结核化疗新药研发取得了较明显进展。作者对近年来抗结核病化疗药物的研究进展作一综述。     

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。     

结核菌耐药的基因及治疗

近年来．随着化疗药物的广泛应用。耐药结核病,尤其是耐多药结核病（MDR-TB）对全球结核病控制造成严重威协。高耐药率和耐多药菌株以及广泛耐药结核病的不断扩散,正日益成为全球结核病控制中的一个重大问题。而我国多耐药结核病疫情属全世界22个高负担国家之一。     

Tb drug resistance: is it really a threat to Africa?

In most of the world and particularly in Eastern Europe, China and India, drug resistance is increasingly seen as a major threat to tuberculosis (TB) control and even to public health and health security. What about in Africa? The conditions for creation of drug resistance exist in most, if not all, African countries, as a result of underinvestment in basic TB control, poor management of anti-TB drugs and virtual absence of infection control measures. The severity of drug resistance is increasing--following outbreaks all over the world of multi-drug resistant TB (MDR) in the 1990's, extensive drug resistant (XDR) TB has now been found in 37 countries, including South Africa. (MDR is, in essence, resistance to the most powerful first-line drugs, and XDR-TB is TB resistant to the most powerful second-line drugs as well.) Worse still, the impact of XDR-TB is magnified among those with HIV infection, giving rise to a remarkably high mortality, and exposing significant weaknesses in both HIV and TB control. In particular, the lack of laboratories capable of carrying out culture and drug susceptibility testing severely limits the capacity of countries even to detect the problem in Africa. This paper analyses the threat of TB drug resistance to health and to TB control in Africa, and puts forward measures to diminish this threat.     

抗结核药物靶点的研究进展

摘要：由结核分枝杆菌(Mycobacterium tuberculosis,Mtb)感染引起的结核病(TB)是世界上最致命的感染性疾病之一。因抗 结核药物的泛用与滥用,细菌耐药问题日渐凸显。近几十年仅有2种抗结核新药上市,由于药物使用中的副作用及其耐药菌株 的出现,急需开展针对Mtb新靶点的药物研究。本文围绕近几年全球最新报道的抗结核药物靶点及其相关化合物进行综述并加 以系统总结,以期在一定程度上为新型抗结核药物的研发提供参考。     

Emerging technologies for monitoring drug-resistant tuberculosis at the point-of-care

Infectious diseases are the leading cause of death worldwide. Among them, tuberculosis (TB) remains a major threat to public health, exacerbated by the emergence of multiple drug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (Mtb). MDR-Mtb strains are resistant to first-line anti-TB drugs such as isoniazid and rifampicin; whereas XDR-Mtb strains are resistant to additional drugs including at least to any fluoroquinolone and one of the second-line anti-TB injectable drugs such as kanamycin, capreomycin, or amikacin. Clinically, these strains have significantly impacted the management of TB in high-incidence developing countries, where systemic surveillance of TB drug resistance is lacking. For effective management of TB on-site, early detection of drug resistance is critical to initiate treatment, to reduce mortality, and to thwart drug-resistant TB transmission. In this review, we discuss the diagnostic challenges to detect drug-resistant TB at the point-of-care (POC). Moreover, we present the latest advances in nano/microscale technologies that can potentially detect TB drug resistance to improve on-site patient care.     

抗结核药物最新进展

结核病是病死率仅次于艾滋病的全球第二大感染性疾病。当前结核病的控制面临一系列挑战。世界卫生组织推荐的结核治疗方案疗程长,对敏感菌和耐药菌感染分别需6个月、20个月的持续治疗。现有抗结核一线化疗药仍为四十多年前所开发,品种有限,选择余地小。此外,多耐药结核病(MDR-TB)及广泛耐药结核病(XDR-TB)的流行,严重阻碍了结核病控制的进展。严峻的结核病防治形势急需抗结核新药的出现。近十年来,抗结核化疗新药研发在沉寂多年后取得了较明显进展。本文介绍了近年上市与处于临床及临床前研究阶段的抗结核新药。     

西安市结核病胸部肿瘤医院抗结核药使用情况与结核分枝杆菌耐药性分析

目的：分析结核分枝杆菌耐药性与抗结核药应用情况相关性,为临床合理使用抗结核药提供参考。方法：对2012年1—12月我院结核分枝杆菌耐药情况和抗结核药的用药频度（DDDs）、限定日费用（DDC）及排序比（B／A）进行统计、分析。结果：1165株结核分枝杆菌对4种一线抗结核药总体耐药率为29．3％（341／1165）,耐多药率为12．0％（140／1165）,单耐药率最高为链霉素（22．8％）、最低为乙胺丁醇（7．0％）;79株耐多药菌株对7种二线抗结核药单耐药率最高为利福喷汀（53．2％）,最低为阿米卡星（1．3％）;一线抗结核药使用较广泛,DDDs较高,二线抗结核药对患者的经济负担较重,DDC较高;静脉用利福平制剂及氟喹诺酮类制剂的用量较大。结论：结核分枝杆菌耐药率升高与抗结核药大量应用具有相关性,应加强药品敏感性监测,合理使用抗结核药。     

论临床结核病耐药性变化趋势的动态监测分析与研究

目的对临床结核病耐药性的变化趋势的动态监测的方法进行探讨。方法选择2008年至2011年经确诊的2000例肺结核患者作为研究对象,对其耐药菌株进行治疗前与治疗后的动态监测,并对药敏结果进行统计与分析,最终确定治疗前后耐药菌谱的变化情况。结果本组2000例肺结核患者的耐药均值在治疗前与治疗后对抗结核药物的耐单药例数是有一定差异的,以乙胺丁醇（Ethambutol,EMB）药物的耐药例数发生了较为明显的变化,耐药性显著增加,前后对比呈显著的统计学差异（P〈0．01）;对丁胺卡那霉素（Amikacin,AMK）、卷曲霉素（Capreomycin,CPM）以及对氨基水杨酸（Sodium Aminosalicylate,PAS）三种药物的初始耐药率及复敏率较高。结论对耐多药肺结核患者的耐药菌株进行动态监测,可以准确获取耐药菌株耐药性信息,具有重要的临床意义与价值;同时对目前使用EMB等药物治疗的方案提出警示与质疑,尽快地开发新一代的毒性低、效率高的抗结核药物是目前解决抗结核治疗困境的一个当务之急。     

Resistant TB: Newer Drugs and Community Approach

Drug resistance in tuberculosis (TB) is a serious problem compromising both the treatment and control programs. Poor usage of the available anti TB drugs has led to progressive drug resistance-multi drug resistance (MDR), extensively drug-resistance (XDR) and even total drug resistance (TDR). While drug sensitive TB is completely curable, MDR-TB is difficult to treat, XDR and TDR are often fatal. Non availability of new drugs to treat drug resistant cases further complicates the problem. The Global Alliance for Tuberculosis Drug Developments, a non-profit organization with the World Health Organization (WHO) as a partner was formed in February 2000 for the development of new drugs. In the last decade this venture has resulted in several promising new antituberculosis drugs like TMC207 (diaryquinoline), PA-824 (nitroimidazo-oxazine), OPC-67683 (nitroimidazo-oxazole) and SQ 109 (diamine compound). Drug resistance in TB is a man made problem. Therefore, while global efforts towards new drug development must continue it is equally important to have a well defined community approach to prevent the emergence of drug resistance to the existing and newer drugs. The present review article discusses some recent drug patents for the treatment of tuberculosis and the appropriate community approach to prevent and treat drug resistant TB.     

Drug-resistant and multidrug-resistant tubercle bacilli

Drug resistant (DR) and multidrug resistant (MDR) tuberculosis (TB) is a consequence of human activity and did not exist before chemotherapeutic drugs were introduced. Monotherapy with various drugs in sequence or other inadequate drug regimens have strongly contributed to the creation of MDR-TB. Such TB strains are mainly prevalent in regions with weak national TB programmes or poor socio-economic environments. Strains may also spread in some communities such as poorly administered prisons. From these and other sources, MDR-TB may spread in the population from which travellers might transfer strains between countries and continents. Therefore an effective surveillance of the resistance pattern of TB bacilli is a demanding task in all countries. In this review some aspects of epidemiology, diagnosis and mechanisms of DR in TB are discussed. MDR-TB is an important international problem of increasing significance for the whole global community.     

Recent advances in new structural classes of anti-tuberculosis agents

Tuberculosis (TB) is one of the most devastating diseases primarily due to several decades of neglect, and presents a global health threat of escalating proportions. TB is the second leading infectious cause of mortality today behind only HIV/AIDS. The impetus for developing new structural classes of anti-tuberculosis drugs comes from the emergence of multi-drug resistant (MDR) strains to commonly used drugs, substantially longer durations of therapy that are needed as a result of resistance, and the resurgence of disease in immuno-compromised patients. Recent years have witnessed emergence of many new structural classes of anti-TB agents, which have exhibited promising activities against drug-sensitive and drug-resistant strains of the causative organism Mycobacterium tuberculosis. These analogs ideally should decrease the overall duration of therapy with improved efficacy, and exhibit mechanisms of action different from those of existing drugs to counter the resistant strains of M. tuberculosis. This review provides a comprehensive literature compilation on advances in the new structural classes of anti-TB analogs reported during the past five years. Our discussion and observations are concentrated on chemotherapeutic potential of alphabetically listed twenty-seven new structural classes of anti-tuberculosis agents that include:- acetamides, 5-arylidene-2-thiohydantoins, benzoxazoles and benzothiazoles, benzoic acid hydrazones, benzoxazines, carbohydrates, chalcones, coumarins, deazapteridines, imidazoles, indoloquinazolinones, isothiosemicarbazones, mycobactins, 1,8-naphthyridines, phenazines, purines, pyridines, N-pyridinylsalicylamides, pyrimidines and thymidines, pyrroles, quinolines, quinoxalines, terpenes, thiadiazine thiones, thiolactomycines, toludines, and triazoles.