抗结核一线药物及结核分枝杆菌的耐药分子机制

近年来涌现出了耐多药结核病(Multidrug-resistanttuberculosis,MDR-TB)/广泛耐药结核病(Extensively drug-resistant tuberculosis,XDR-TB)。MDR-TB是指由耐异烟肼和利福平两种或以上抗结核药物的结核分枝杆菌引起的结核病。XDR-TB是指不...     

结核病表现的多态性及其对策

［摘要］概述结核病在慢性感染发病诊断治疗过程中的多种临床表现，及其应对策略，如菌阴结核病、菌阳肺结核、特殊类型的结核病、非结核分枝杆菌病和免疫力低下性结核病等。重点介绍严重耐药结核病（XDR TB）、耐多药结核病（MDR TB）的治疗，以及无变应性结核病等。     

结核分枝杆菌耐药性快速检测技术研究新进展

近年来,多耐药结核病仍是严重威胁人类健康的疾病,尤其是严重耐多药结核病(XDR)的出现,大有成为新的不治之症的可能。由于不规范的治疗是     

结核病患者耐多药的影响因素分析

<正>结核病是由结核杆菌感染导致的慢性传染病,可侵及多个脏器,每年导致数百万人患病,已成为世界传染病的第二大死亡原因~([1])。而在治疗结核病过程中出现的耐药结核病(DR-TB)甚至是耐多药结核病(MDR-TB)及广泛耐药结核病(XDR-TB),更是为结核病的彻底治愈造成了极大困难~([2])。多项研究认为,导致结核病患者产生耐多药的危险因素有很多,例如既往病史、不良生活习惯或人类免疫缺陷病毒(HIV)感染等[3],但是不同研究之间分歧比较大。因此,本研究旨在较综合地分析结核病患者耐多药的危险因素,从而为降低耐多药结核病发生率提供参考依据。1资料与方法     

耐多药和广泛耐药肺结核患者疗效分析

<正>耐药结核病尤其是耐多药结核病(MDR-TB)和广泛耐药结核病(XDR-TB)的流行与传播使全球结核病控制工作面临严峻的考验。近20年来,尽管国际国内的相关指南中提出了多种化学治疗方案,但仍然不能有效地治疗耐多药和广泛耐药结核病并控制其流行。2007—2010年的临床研究结果表明,现有治疗耐药结核病的化学治疗方案效果差,治愈率和治疗成功率分别约为35%和50%[1]。我院(太原市第四人民     

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。     

结核外科的一些特殊问题

我国结核病流行形势十分严峻,对人民群众健康的危害十分严重。近年来,我国结核病防治领域耐多药结核病(MDR-TB)和严重耐多药结核病(XDR-TB)日益突出。结核外科也面临新的挑战。参考相关文献并结合自身临床实践对结核外科工作中遇到的一些特殊问题进行总结。     

耐多药肺结核88例抗结核药物不良反应发生情况分析

<正>耐药结核病尤其是耐多药结核病(MDR-TB)和广泛耐药结核病(XDR-TB)的流行与传播使全球结核病控制工作面临严峻的考验。2007—2010年的临床研究结果表明,现有治疗耐药结核病的化学治疗方案效果差,治愈率和治疗成功率分别约为35%和50%[1]。而药物不良反应(ADR)是干扰结核病防治策略的重要因素之一[2,3]。耐多药结核病用药种类多,剂量大,疗程长,导致不良反应的可能性较一线抗结核药物更     

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,...     

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。     

Thioridazine cures extensively drug-resistant tuberculosis (XDR-TB) and the need for global trials is now!

Thioridazine (TDZ) has been shown to have in vitro activity against multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis, to promote the killing of intracellular MDR and XDR strains and to cure the mouse of antibiotic-susceptible and -resistant pulmonary tuberculosis (TB) infections. Recently, TDZ was used to cure 10 of 12 XDR-TB patients in Buenos Aires, Argentina. At the time of writing, it is being used for the therapy of non-antibiotic-responsive terminal XDR-TB patients in Mumbai, India, on the basis of compassionate therapy and although it is too early to determine a cure, the patients have improved appetite, weight gain, are afebrile and free of night sweats, and their radiological picture shows great improvement. Because XDR-TB is essentially a terminal disease in many areas of the world and no new effective agents have yet to yield successful clinical trials, global clinical trials for the therapy of XDR-TB are urgently required.     

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.     

Cytokines as immunomodulators in tuberculosis therapy

The use of cytokines for therapeutic purposes is limited by their high cost and toxicity. Nevertheless, the emergence of extensively drug-resistant tuberculosis (XDR TB), for which chemotherapy is ineffective, has again made cytokine-based therapy attractive as one of the last available options. The results of clinical trials treating pulmonary tuberculosis with cytokines have not been encouraging, making it clear that therapeutic strategies utilizing a single cytokine are inadequate. To develop effective cytokine-based XDR TB therapies, more basic research will be needed to achieve a better understanding of how cytokines promote a successful immune response. We not only have to investigate cytokines already known to participate in tuberculosis, but also the role of other cytokines and chemokines that may enhance both the mycobacterial killing activity of effector cells and the restriction of bacterial intracellular multiplication. There are already several patents involving cytokines for therapeutic use, in the hope of stimulating the immune system in a variety of infectious diseases, including tuberculosis. The validity of these patents needs to be reassessed from a clinical standpoint, and new applications of patents concerning cytokines potentially useful in XDR TB treatment should be encouraged.     

Effective therapy with the neuroleptic thioridazine as an adjunct to second line of defence drugs, and the potential that thioridazine offers for new patents that cover a variety of "new uses"

New and active infections of tuberculosis continue to increase globally. Although antibiotic susceptible infections can be readily cured with isoniazide and rifampicin, infections resistant to these two antibiotics, named Multi-Drug Resistant TB (MDR TB), are problematic for therapy, extol high costs in terms of human suffering and finances, and when these MDR infections progress to Extensive Drug Resistant TB (XDR TB) status, they are not only difficult to treat, they produce high levels of mortality regardless of therapeutic modality employed. The neuroleptic thioridazine (TZ) has been shown to have wide spectrum in vitro and ex vivo activities against antibiotic susceptible, MDR and XDR strains, and has been successfully used for curing mice of active tuberculosis produced by antibiotic susceptible and MDR strains, and has cured 10 out of 12 XDR TB patients when used in combination with three antibiotics to which the XDR TB patients were non-responsive. Mycobacterium tuberculosis TZ has been recommended for "Compassionate Therapy" of MDR/XDR TB infections whose prognoses are significantly serious and anticipated to result in mortality. This review of TZ activity and its potential to cure MDR/XDR TB supports the contention that this neuroleptic offers patenting opportunities for "New Use". The motivation for patents therefore is expected to rapidly bring TZ to the forefront for therapy of MDR/XDR TB and therefore, the striving for new patents is expected to contribute to the prevention of new infections of antibiotic resistant tuberculosis.     

Promising therapy of XDR-TB/MDR-TB with thioridazine an inhibitor of bacterial efflux pumps

Global rates of pulmonary tuberculosis (TB) continue to increase. Moreover, resistance of the causative organism Mycobacterium tuberculosis to the two most effective anti-TB medications continue to rise. Now, multi-drug resistant TB (MDR-TB) has progressed to extensively drug resistant TB (XDR-TB) - a M. tuberculosis organism that is resistant to the most effective second line drugs available for the treatment of TB. This review provides detailed, significant evidence that supports the use of an old neuroleptic compound, thioridazine (TZ), for the management of MDR-TB and XDR-TB infections and which has been shown to inhibit efflux pumps of bacteria. The argument has been previously presented but no one seems to be listening - and the disease continues unabated when there is a very good probability that the suggested drug will prove to be effective. When the prognosis is poor, available therapy predictably ineffective and death is inevitable, compassionate therapy with TZ should be contemplated. The risks are small and the rewards great.     

山东省耐多药肺结核可疑者筛查情况分析

目的回顾性分析山东省全球基金耐多药肺结核防治项目中可疑者筛查情况,探索并完善耐多药肺结核患者的发现策略。方法在项目地区以耐多药肺结核患者的密切接触者、涂片阳性的慢性和复治失败、初治失败、复发、返回及治疗3个月末痰涂片仍阳性的初治涂阳患者等重点人群为主要筛查对象,进行结核菌培养和药敏试验,分析不同人群中耐多药及广泛耐药肺结核的筛出情况。结果开展培养的4318例涂片阳性的耐多药肺结核可疑者中,培养阳性3315例(82.5%);开展药敏试验的3296例可疑者中,422例(14.3%)被诊断为耐多药肺结核,16例(0.5%)被诊断为广泛耐药肺结核,其中复治失败患者中耐多药及广泛耐药肺结核检出率最高,为64.5%,初治失败患者中耐多药及广泛耐药肺结核检出率较高,为41.2%,新患者中耐多药及广泛耐药肺结核检出率较低,仅为6.6%。结论重点人群筛查是一种高效的耐多药肺结核患者的筛查策略,值得在山东省其他地市推广应用。     

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.