临床肺结核患者非结核分支杆菌分离及其分析

目的 探讨河南省临床肺结核患者非结核分支杆菌（NTM）分布、耐药情况及临床特点。方法 对2001年7月～2002年6月河南省结核病耐药监测中痰分支杆菌培养阳性的1581株菌株用TCH和PNB进行菌型初步鉴定;采用比例法对四种抗结核药物：INH,RFP,EMB和SM进行药敏试验,并对分离出NTM的21例患者临床资料进行分析。结果 临床肺结核患者痰NTM分离率为1．33％;耐药率为90．5％;耐多药率为76．2％;主要症状依次为咳嗽、咳痰,发热,咯血等;病灶多累及2个及以上肺野。结论 河南省NTM处于较低流行水平;由于特殊人群中HIV／AIDS的流行,对NTM感染和NTM病应予高度重视。     

非结核分支杆菌16例药敏特点分析

目的:分析我院2008-2010年非结核分支杆菌(NTM)的耐药情况.方法:对2008年3月～2010年3月无锡市传染病医院结核病实验室所做结核分支杆菌药敏试验的279例菌株用TCH和PNB进行菌型初步鉴定,采用绝对浓度法对12种抗结核药物:异烟肼、利福平、链霉素、乙胺丁醇、吡嗪酰胺、奥氟星、对氨基水杨酸、卷曲霉素、力克肺疾、利福喷丁、丁胺卡那和丙硫异烟胺进行药敏试验,并对分离出来的16株NTM的药敏结果进行分析.结果:279例菌株中NTM分离率为5.73%,有3例全耐药;16株NTM对吡嗪酰胺呈现全耐药;除对丁胺卡那的低浓度与高浓度耐药率差异有统计学意义外,对其他10种药物低、高浓度的耐药率差异无统计学意义.说明很多非结核分支杆菌对抗结核药物呈天然的抗药性.结论:我市非结核分支杆菌处于较低的流行水平,针对非结核分支杆菌的高耐药性.需要制定新的、更有效的治疗手段,对NTM感染和NTM病应予高度重视.     

西藏自治区非结核分枝杆菌耐药特点及临床特征初步分析

目的探讨西藏自治区非结核分枝杆菌(NTM)的耐药情况及临床特点。方法收集2008年3月至2010年7月西藏自治区疾病预防控制中心结核病实验室从患者痰标本分离培养的分枝杆菌培养物,用PNB/TCH鉴别培养基培养进行菌种鉴定,采用WHO推荐的比例法进行4种一线药物异烟肼(INH)、利福平(RFP)、乙胺丁醇(EMB)和链霉素(SM)的药敏试验,并结合临床资料分析NTM病例的临床特征。结果共收集到412株分枝杆菌培养物,经鉴定,非结核分枝杆菌18株,占4.4%。对INH、RFP、SM和EMB的耐药率分别为88.9%、77.8%、94.4%和22.2%。耐多药率为77.8%。总耐药率100%。临床主要症状为咳嗽、咳痰、发热、咯血等;肺部病变范围广,以中年患者多见。结论西藏自治区结核病病原同样存在NTM,NTM对INH、RFP和SM不敏感。NTM肺病的治疗方案有待规范。     

48例非结核分枝杆菌肺病的临床分析

资料与方法 1.一般资料:采用Bac T/ALERT快速分支杆菌检测系统BD960行初培养,再用0.5%对硝基苯甲酸(PNB)鉴别培养基培养及药敏试验,同时再做罗氏固体培养基进行菌种培养鉴定试验。我院结核一病区2011年1月-2015年1月间住院确诊的非结核分枝杆菌(NTM)肺病患者48例为病例组,对同期入院的肺结核患者按照随机抽取120例为对照组,病史最长的20年,     

肺科患者痰标本分离非结核分枝杆菌47株分析

目的探讨临床肺疾病患者非结核分枝杆菌（NTM）分布，耐药情况及临床特点。方法对1959例患者的痰标本进行分枝杆菌培养。对培养阳性的910份标本中的860份进行药敏实验与菌型初步鉴定，并对分离出的47株NTM与相对应的44例临床资料进行对比分析。结果NTM检出率5．5％，总耐药率93．6％，单耐药率平均48％，RH两联耐药率37％，含RH多联耐药率28％。临床症状多为咳嗽，咳痰，发热，部分病例咯血及慢性病症，治疗效果不明显。结论NTM感染及引发的疾病必须引起医学检验与临床的重视，连续痰鉴定为NTM者为NTM肺病高度可疑者，实验室有必要进一步开展NTM的菌种鉴定技术。诊断耐多药肺结核，必须除外NTM肺病。     

非结核分支杆菌病并发艾滋病的药物治疗

非结核分支杆菌(NTM)病是艾滋病患者全身细菌感染常见的原因,NTM病并发艾滋病的治疗已被学者们关注.介绍NTM病并发艾滋病的治疗原则、治疗药物及药物间的相互作用,并推荐几种常见NTM病的治疗方案.     

非结核分支杆菌病药物治疗进展

非结核分支杆菌亦称非典型分支杆菌，指结核杆菌以外(不包括麻风杆菌)的分支杆菌，由该菌感染所致疾病叫非结核分支杆菌病(NTM)。长期以来国际一致认为结核病与NTM比较，肺结核发病率逐年下降，NTM发病逐年上升。自1986年以后WHO宣布结核病呈上升趋势，而这一时期少有NTM报告。由于近年艾滋病(AIDS)在全球范围流行，结核和NTM与AIDS有共染性，并相互促进病理发展，据报道AIDS患者中NTM合并感染多达30％。     

一线抗痨药物均耐药结核菌体外组合药物作用效果研究

目的对临床主要一线抗痨药异烟肼（isoniazidum，H）、利福平（rifampin，R）、链霉素（streptomycin，S）和乙胺丁醇（ethambatal，E）均耐药结核菌株进行体外组合药物作用效果研究，拟探讨结核病主要一线药物均耐药再联合用药时，化疗是否有效的临床耐多药结核病治疗问题。方法采用BacT／ALERT3D分支杆菌培养系统对10株常规L-J法药敏至少对H、R、S和E（或同时对R）依赖的结核菌株及H37Rv标准敏感菌株，以MIC和平均血药峰浓度分别进行H、R、S及E单一药物和H＋E＋S及H＋S＋E＋R组合药物药敏平行实验；将3D培养42d结果为阴性的实验瓶混悬液再平行转种于L-J管继续培养，以确定药物作用的效果（观察细菌是否真正被药物杀死）。结果单一药物3D法与L-J法的药敏结果基本一致。3D法单一药物均耐药菌株组合药物MIC和平均血药峰浓度实验结果显示不同程度报告阳性时间延长趋势。3D法单一药物耐药，组合药物未报告阳性的实验瓶，转种于L-J管继续培养均报告阳性。病例追踪10株分离株均为一线正规化疗失败的复治肺结核患者。结论小样本菌株实验研究结果提示：体外3D法H、R、S及E单一药物均耐药的临床结核菌株，组合药物（MIC和平均血药峰浓度）对其细菌可有不同程度的相对抑制作用，但没有最终协同杀灭细菌，其实验结果与患者临床疗效相符合。     

非结核分枝杆菌耐药性分析

非结核分支杆菌病系由结核分支杆菌和麻风分支杆菌以外非结核分支杆菌(nontuberculosis mycobacteria,NTM)引起的疾病。非结核分支杆菌原称为非典型分枝杆菌(atypical mycobacteria),其特性有别于结核分枝杆菌,如对酸、碱比较敏感;对常用的抗结核菌药物较耐受;生长温度不如结核分枝杆菌严格;多存在于环境中;为条件致病菌。可因引起结核样病变而     

64例非结核分枝杆菌对二线抗痨药的耐药性分析

目的:观察分析非结核分枝杆菌的耐药情况。方法:收集2012年10月~2013年4月陕西省结核病院痰Bactec 960培养阳性,菌型鉴定为非结核分枝杆菌的菌株对二线抗结核药耐药性情况。结果:非结核分枝杆菌64例占痰培养阳性914例的7.0%。耐药菌62株,总体耐药率96.8%。耐药次序为对氨基水杨酸、卷曲霉素、阿米卡星、莫西沙星、左氧氟沙星、丙硫异烟胺。耐6种药4株(6.25%),耐5种药8株(12.5%),耐4种药23株(35.9%),耐3种药22株(34.3%)。结论:NTM耐药率高,应对可疑NTM肺病及早做菌型鉴定及药物敏感性测定,根据药敏制定合理的治疗方案,研究抗NTM新药是目前的迫切需要。     

Drug-resistant tuberculosis: what are the treatment options?

Drug-resistant tuberculosis (DR-TB) is an emerging global health threat as treatment involves complex multiple drug regimens, which are longer and more toxic than standard therapy and yet have worse outcomes. In the presence of resistance to one or more first-line drugs, an alternative regimen should be designed. A major problem is the almost complete lack of published evidence regarding the optimal drug combinations and duration of treatment for the different types of DR-TB. Current principles, some of which are based on expert opinion, are that at least three new anti-TB agents should be added to a failing regimen and four agents when multidrug resistance is suspected. All first-line oral anti-TB agents to which the Mycobacterium tuberculosis strains are susceptible should be used, plus one fluoroquinolone. In addition, one injectable anti-TB agent and one or more second-line oral anti-TB agents should be added to the regimen until the target number of drugs is reached. The duration of treatment depends on the type of drug resistance, the type and number of drugs used in the regimen, and the extent of the disease. All forms of DR-TB should receive daily, not intermittent, therapy and all doses should be directly observed. Because of the high rate of adverse drug effects, careful monitoring and appropriate management of these adverse reactions are important to achieve successful treatment. Supportive measures, such as adequate nutrition along with emotional and social supports, are an important part of the treatment. Careful consideration is required when dealing with pregnant or lactating women and HIV co-infected patients, as well as in treatment of extrapulmonary DR-TB.     

Emerging therapeutic targets in tuberculosis: post-genomic era

Every minute, somewhere in the world four people die from tuberculosis (TB), yet it has been nearly 40 years since a novel drug was introduced to treat this disease. The ever increasing number of TB cases together with the advent of multi-drug resistant (MDR) TB, has stimulated the search for novel anti-TB agents. An array of novel drug targets is provided by the mycobacterial cell wall, whose integrity is essential for bacterial viability. Over the years researchers have identified potential drug targets that are associated with the synthesis of various cell wall constituents. This classic approach, together with the unravelling of the Mycobacterium tuberculosis genome sequence, has placed TB drug research in an unprecedented position. An entire new set of genetic and bioinformatic tools for probing potential drug targets is now available. As therapies using first-line drugs like isoniazid (INH) or rifampin in combination with second-line drugs, like ethambutol (EMB) still continues, a number of substituted fluoroquinolones are being considered as the new generation of anti-TB drugs for their favourable pharmacokinetic profile and excellent oral bioavailability. In this review, the future of anti-TB drugs is discussed with reflection on the structure and biosynthesis of cell wall constituents that are potential drug targets. The importance and relevance of the M. tuberculosis genome sequence for the development of novel anti-TB drugs, have also been underscored.     

Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria

Nontuberculous mycobacteria (NTM) are increasingly recognized as causative agents of opportunistic infections in humans. For most NTM infections the therapy of choice is drug treatment, but treatment regimens differ by species, in particular between slow (e.g. Mycobacterium avium complex, Mycobacterium kansasii) and rapid growers (e.g. Mycobacterium abscessus, Mycobacterium fortuitum). In general, drug treatment is long, costly, and often associated with drug-related toxicities; outcome of drug treatment is poor and is likely related to the high levels of natural antibiotic resistance in NTM. The role of drug susceptibility testing (DST) in the choice of agents for antimicrobial treatment of NTM disease, mainly that by slow growers, remains subject of debate. There are important discrepancies between drug susceptibility measured in vitro and the activity of the drug observed in vivo. In part, these discrepancies derive from laboratory technical issues. There is still no consensus on a standardized method. With the increasing clinical importance of NTM disease, DST of NTM is again in the spotlight. This review provides a comprehensive overview of the mechanisms of drug resistance in NTM, phenotypic methods for testing susceptibility in past and current use for DST of NTM, as well as molecular approaches to assess drug resistance.     

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.     

某区322株结核杆菌的耐药性分析

目的了解惠州市结核病防治院322株痰培养阳性结核杆菌的耐药情况,为临床合理用药提供理论依据。方法以我院322株痰培养阳性的结核杆菌为研究对象,用比例法进行一线结核用药的药敏实验。结果 322株结核分枝杆菌对4种抗结核药物全部耐药者36例,占10.84%;以耐链霉素为最高,占35.8%。结论惠州市结核病耐药情况仍然十分严峻,应加强结核病临床治疗的管理,制定合理化疗方案,防止耐药菌传播。     

利福霉素类药物治疗结核病的临床应用研究进展

结核病是由结核分枝杆菌复合群引起的传染性疾病，是全球主要的流行病种之一。利福平是当前最主要的一线抗结核药物，因其长期应用和不规范治疗，利福平耐药逐渐增加，利福喷丁、利福布汀等利福霉素类衍生物在抗结核治疗方面起到了重要作用。基于利福霉素类药物的药理及药动学特性，对该类药物在结核病治疗中进行最优用药选择分析，并对该类药物与其他抗结核药物联用进行综述，旨在为利福霉素类抗结核药物的临床用药提供文献依据。     

Increased rifampicin resistance in blood isolates of meticillin-resistant Staphylococcus aureus (MRSA) amongst patients exposed to rifampicin-containing antituberculous treatment

The aim of this study was to determine the rifampicin (RIF) resistance rate of meticillin-resistant Staphylococcus aureus (MRSA) amongst patients with MRSA bacteraemia who have or have not been exposed to RIF-containing antituberculous (anti-TB) treatment. From 2000 to 2008, patients with MRSA bacteraemia and previous exposure to RIF-containing anti-TB therapy were selected. Patients matched for sex, age and time of culture of MRSA bacteraemia but without exposure to anti-TB therapy were selected as a control group. A total of 139 patients, comprising 49 with RIF exposure and 90 without RIF exposure, were analysed. The RIF resistance rate was higher in patients with previous RIF exposure (61.2% vs. 20.0%; P<0.001). The minimum inhibitory concentration of RIF that inhibited 50% of MRSA isolates (MIC(50)) for the study group was also higher (128 mg/L vs. 0.015 mg/L; P<0.001). The mortality rate was higher in the study group (59.2% vs. 41.1%; P=0.041). MRSA isolates recovered from patients with current usage of a RIF-containing anti-TB regimen were more likely to be resistant to RIF (87.5% vs. 36%; P=0.001), with higher MIC(50) values (256 mg/L vs. 1mg/L; P=0.002), and resulted in a higher mortality rate than isolates from patients with remote usage of an anti-TB regimen (79.2% vs. 40%; P=0.005). Multivariate analysis showed that current anti-TB drug usage was the only risk factor for RIF resistance [odds ratio (OR)=7.457, 95% confidence interval (CI) 1.581-35.167] and mortality (OR=7.201, 95% CI 1.583-32.766). Given the high rate of RIF resistance in patients with prior anti-TB treatment, RIF susceptibility testing should be performed before considering combination treatment of RIF in MRSA infection.     

Challenges Facing Antitubercular Therapy: New Drugs and Delivery Systems

Tuberculosis (TB) has again emerged as a challenging disease, victimizing a large section of the world population. Long duration of therapy, drug resistance, side effects associated with large doses of number of drugs, and economic reasons have resulted in poor patient compliance and in ineffective anti-TB therapy. In addition, drug-resistant strains of tubercle bacilli have further compounded the problem. In this article challenges facing present therapy, the mode of tuberculosis infection, challenges facing fixed-dose combination (FDC) formulation, new anti-TB molecules from the modification of existing anti-TB drugs for better activity, new molecules acting on the novel targets for reducing bacterial pathogenicity, antibiotics and nonantibiotics exhibiting anti-TB activity, and new drug delivery systems are discussed.