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。     

抗结核药物的临床合理应用

<正>结核病是一个严重的公共卫生问题。目前结核病全球性疫情回升,其中耐多药结核病(MDR-TB)和广泛耐药结核病(XDR-TB)尤其引人瞩目。2008年中国报告的肺结核的发病数和死亡数均居法定甲乙类传染病的第2位,2000年中国流行病抽样调查表明,结核分枝杆菌总耐药率为27.8%,可见中国结核病疫情和耐药趋势不容乐观。     

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     

临床结核病耐药性变化趋势的动态监测观察

目的分析研究临床结核病耐药变化趋势,为结核病诊治提供科学的用药依据。方法收集结核病患者结核分枝杆菌1080株,采用比例法对4种不同的抗结核药物进行耐药性试验分析。结果在1080株菌株中,有354株菌株耐药,总耐药率为32.7%。其中183株为耐多药结核病(MDR-TB),耐多药率为16.9%,48株为广泛耐药结核病XDR-TB,广泛耐药率为4.44%。结核病患者趋向于抗结核药品中,耐药率最高的为链霉素(SM),其次是异烟肼(INH)、利福平(RFP)、乙胺丁醇(EMB)。结论 MDR-TB耐药率有明显上升趋势,应采取有效的措施予以控制,同时加强耐要性的动态监测与研究有着重要意义。     

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。     

含胸腺肽肠溶胶囊方案治疗耐多药肺结核疗效分析

<正>根据2010年全国第5次结核病流行病学抽样调查报告,我国结核病的流行特点有低递降率、高耐药率[1]。耐多药结核病(multidrug-resistant tuberculosis,MDR-TB)是指至少同时耐异烟肼、利福平2种及以上药物,MDR-TB已成为一个严重的公共卫生问题,成为结核病控制规划的重大障碍[2]。     

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     

抗结核药物的研究新进展

结核病是一种严重危害人们身体健康的慢性传染性疾病,是目前全球重大的公共卫生问题和社会问题之一.研究显示,全世界约1/3的人口感染结核菌,每年约200万人因结核病而死亡[1].2009年全国结核病发病率为98/10万,结核病发病人数达130万[2].近年来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)的流行与传播使本已严峻的全球结核病防治形势变得更为复杂与紧迫.本研究就近年来发现的具有抗结核应用前景的药物研究情况综述如下.     

Problems of multidrug- and extensively drug-resistant TB

Worldwide, it is thought that in 2010 around 9 million people developed tuberculosis (TB) and around 1.5 million people died from the disease. Standard therapy (6 months of rifampicin and isoniazid, plus pyrazinamide and ethambutol for the first 2 months) is recommended for newly diagnosed active respiratory TB and is effective if taken correctly. However, its effectiveness can be compromised by a number of factors including poor adherence (e.g. because of the long duration of treatment, occurrence of unwanted effects) or inadequate drug levels for other reasons (e.g. drug-drug interactions, poor quality medicines). These factors also contribute to the development of resistance to one or more of the drugs. Multidrug resistant TB (MDR-TB) is defined as TB with resistance to both rifampicin and isoniazid. Patients with MDR-TB are treated with a combination of first-line and second-line drugs based on the results of drug susceptibility testing. The treatment is longer, less effective, less tolerable, and more expensive than standard therapy, and involves the use of injectable drugs. Extensively drug-resistant TB (XDR-TB; defined as TB with resistance to rifampicin and isoniazid, and to at least one fluoroquinolone and one second-line injectable agent such as amikacin or capreomycin) is now emerging. Here we highlight patient groups at increased risk of MDR- and XDR-TB, and discuss how to investigate, manage and treat them.     

Drug-resistant tuberculosis in the WHO European Region: An analysis of surveillance data

To review the latest information about levels of anti-tuberculosis (TB) drug resistance in the European Region of the World Health Organization (WHO) and time-trends in multidrug-resistant TB (resistance to isoniazid and rifampicin; MDR-TB) over the past fifteen years.We analysed data on drug resistance among new and previously treated TB cases reported from 1997 to 2012. Data are collected in surveys of representative samples of TB patients or from surveillance systems based on diagnostic drug susceptibility testing.A total of 15.7% (95% confidence limits (CI): 9.5–21.9) of new and 45.3% (95%CI: 39.2–51.5) of previously treated TB cases are estimated to have MDR-TB in the Region. Extensively drug-resistant TB (MDR-TB and resistance to fluoroquinolones and second-line injectables; XDR-TB) had been reported by 38 of the 53 countries of the region (72%). The proportion of MDR-TB cases with XDR-TB is 11.4% (95%CI: 8.6–14.2). Between 1997 and 2012, population rates of MDR-TB declined in Estonia, Latvia and Germany and increased in the United Kingdom, Sweden and Tomsk Oblasts of the Russian Federation.Surveillance of drug resistance has been strengthened in the WHO European Region, which has the highest proportions of MDR-TB and XDR-TB ever reported globally. More complete data are needed particularly from the Russian Federation.     

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.     

Drug-resistant tuberculosis in Ethiopia: problem scenarios and recommendation

Tuberculosis (TB) is a major public health problem in Ethiopia. This review is prepared to indicate possible future challenges related to tuberculosis control and it includes previous reports of drug-resistant surveys in Ethiopia. Drug-resistant TB, both initial and acquired, was reported from different regions of the country. In studies from 1984 to 2001, the initial resistance to isoniazid ranges from 2% to 21% and initial resistance to streptomycin ranges from 2 to 20%. Multidrug-resistance (MDR) TB defined as resistance to at least isoniazid and rifampicin was also reported in about 1.2% of new cases and 12% of re-treatment cases. In all studies which included ethambutol susceptibility test, ethambutol resistance is either nil or very low (below 0.5%). All MDR isolates were susceptible to ethambutol. Treatment and re-treatment regimens recommended by the National TB/Leprosy Control Program could be effective on all cases other than those with MDR-TB. MDR-TB is difficult to cure. Therefore, special emphasis should be given to control the spread of MDR-TB. Lack of control efforts may lead to the increased resistance to both first- and second-line drugs. A well supported and controlled special treatment unit, which uses both first-line and second-line drugs is required for a proper management of these cases and for effective control of the spread of MDR-TB. A uniform susceptibility to ethambutol can be taken as an advantage to develop standard low-cost re-treatment regimen for MDR-TB patients.     

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.     

Overview of anti-tuberculosis (TB) drugs and their resistance mechanisms

One-third of the world's population is infected with Mycobacterium (M.) tuberculosis. Tuberculosis continues to be the most common infectious cause of death and still has a serious impact, medically, socially and financially. Multidrug-resistant tuberculosis (MDR-TB), caused by tubercle bacilli that are resistant to at least isoniazid and rifampin, is among the most worrisome elements of the pandemic of antibiotic resistance because TB patients for whom treatment has failed have a high risk of death. Drugs used to treat tuberculosis are classified into first-line and second-line agents. First-line essential anti-tuberculosis agents are the most effective, and are a necessary component of any short-course therapeutic regimen. The drugs in this category are isoniazid, rifampin, ethambutol, pyrazinamide and streptomycin. Second-line anti-tuberculosis drugs are clinically much less effective than first-line agents and elicit severe reactions much more frequently. These drugs include para-aminosalicylic acid (PAS), ethionamide, cycloserine, amikacin and capreomycin. New drugs, which are yet to be assigned to the above categories, include rifapentine, levofloxacin, gatifloxacin and moxifloxacin. Recently there has been much development in the molecular pharmacology of anti-tuberculosis drugs. This review summarizes information for isoniazid, rifampicin, ethambutol, pyrazinamide, and fluoroquinolones, and describes their resistance mechanisms.     

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.     

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。     

Pharmacophore combination as a useful strategy to discover new antitubercular agents

The present study is aimed at combining two well-known pharmacophores (pyrazoline and benzoxazole nucleus) to design and synthesize a series of substituted pyrazoline-based benzoxazole derivatives. In vitro antitubercular evaluation against Mycobacterium tuberculosis H37Rv, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains showed that most of the target compounds displayed potent activity (MIC ~1.25–25 μg/mL) where few compounds were found to be better than isoniazid against MDR-TB (MIC = 3.25 μg/mL) and XDR-TB (MIC = 12.5 μg/mL). Cytotoxicity assay of these active compounds in VERO cell lines displayed good selectivity index. In order to gain insights into the plausible binding motifs, the target compounds were docked into enoyl-acyl carrier protein reductase, a molecular target of isoniazid. All the docked compounds occupied the same hydrophobic binding pocket and interacted mostly by dispersion interactions. Contribution of the three pharmacophoric fragments (pyrazoline, benzoxazole and aryl ring) toward protein–ligand binding was evaluated at semi empirical quantum mechanics level. The interaction energies suggested that most of the binding was governed by the benzoxaxole moiety followed by pyrazoline and aryl rings.