我院2019～2020年非结核分枝杆菌感染及耐药性分析

目的 了解我院2019～2020年非结核分枝杆菌(Nontuberculous mycobacteria,NTM)感染及耐药情况。方法 采用NTM配套试剂,对我院2019～2020年送检的标本进行培养鉴定和药敏试验。结果 检出NTM 114株,主要包括胞内分枝杆菌、龟/脓肿分枝杆菌、堪萨斯分枝杆菌和鸟分枝杆菌;感染年龄集中在51～70岁;仅RIB、FOX、AMK、MOX和CLR耐药率低于30.0%。结论 NTM耐药程度严重,耐药谱差异大,对传统抗结核药物已基本失效,药敏试验对临床用药具有指导意义。     

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。     

《国外医药抗生素分册》第28卷1-6期（2007年）目次检索

药研动态极端环境微生物源活性物质的研究进展(综述)28(1):1喹诺酮诱发关节病的致病机理(编译)28(1):6解脲脲原体耐药机制研究进展(综述)28(1):10铜绿假单胞菌对β-内酰胺类抗生素的耐药机制和检测方法(综述)28(1):14微生物来源的受体拮抗剂研究进展(综述)28(1):19Ser/Thr蛋白激酶信号转导系统——抗结核药物筛选的新靶(综述)28(2):50抗结核分枝杆菌持留菌的药物研究进展(综述)28(2):56结核分枝杆菌中的复苏促进因子(综述)28(2):61分枝杆菌的多相分类鉴定(综述)28(2):64治疗结核新药和药物作用靶位(编译)28(2):70结核病的现行疗法和新药开…     

非结核分枝杆菌的耐药特点初步分析

目的分析本院2012年~2016年5年来非结核分枝杆菌(NTM)的感染趋势、分布及耐药情况。方法对2012年~2015年5年医院确定为NTM的菌种用传统的生化反应法进行菌种鉴定,对鉴定为NTM的菌株采用比例法进行链霉素(SM),异烟肼(INH),利福平(RFP)和乙胺丁醇(EMB)的药物敏感性试验。结果 5年间共收集到11298株分枝杆菌,其中分离出NTM331株,占2.93%。对INH、SM、RFP和EMB的耐药率分别为96.4%、90.6%、83.7%、77.3%。NTM临床症状酷似MTB引致的结核病,一线抗结核药物治疗疗效差甚至无效。结论虽然我院由NTM引起的肺病比例低于全国水平但NTM的高耐药率和逐年上升趋势应引起重视有待解决的是研制新药与更有效的治疗手段。     

45例非结核分枝杆菌肺病临床特征及耐药特点分析

目的分析我院近5年来非结核分枝杆菌(NTM)肺病临床特征及耐药特点。方法对2006年1月至2011年12月我院检验科分枝杆菌实验室分离、培养的分枝杆菌培养物进行菌种鉴定、耐药性统计及其每份标本相对应的临床资料分析总结。结果我院2006年至2011年NTM的平均分离率0.91%,远低于全国水平。NTM对异烟肼(INH)、对氨基水杨酸(PAS)耐药率最高,对阿米卡星(AMK)耐药率最低,同时耐INH、利福平(RFP)和至少耐1种药分别为62.22%和91.11%。结论 NTM肺病病程长,临床症状无特异性,耐药率高,需要及早行细菌学培养、菌株鉴定和药敏试验。     

靶点特异性抗结核分枝杆菌药物筛选模型的建立及应用

目的构建靶点特异性抗结核分枝杆菌药物筛选模型。方法通过诱变剂和诱变条件的考察,确定筛选新生霉素特异性超敏感菌株和超耐药菌株的最佳方案。利用野生株、超敏感菌株与超耐药菌株的活性差异,建立抗结核分枝杆菌药物筛选模型,并对175个化学合成拟抗结核分枝杆菌化合物进行初筛。结果通过UV-Li Cl、微波等诱变方法处理后,得到新生霉素特异性超敏感菌株和超耐药菌株,其MIC值分别为0.4和200 mg·L~(-1)。应用所构建的模型筛选获得一个阳性先导化合物CZQ-06+。结论成功构建了靶点特异性抗结核分枝杆菌药物筛选模型。     

尿道偶然分枝杆菌的感染和耐药分析1例报道并文献复习

<正>非结核分枝杆菌(NTM)是指排除结核分枝杆菌复合群和麻风分枝杆菌以外的其他分枝杆菌。NTM广泛存在于自然界^[1]。仅部分NTM对人体致病，故为条件致病菌^[2]。随着NTM检测手段的更新和投入，NTM的检出率也随着增加，由于受环境和地域等诸多因素的影响，不同地区NTM的发病率也呈现出很大的差异性。本文主要探讨1例尿道感染偶然分枝杆菌的检出、鉴定、药敏及相关治疗情况。1病例资料患者男，12岁，学生，因血尿和尿道感染而就诊。     

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。     

获得性免疫缺陷综合征合并分枝杆菌感染患者的免疫学特征与耐药性分析

目的：分析获得性免疫缺陷综合征(acquired immunodeficiency syndrome,AIDS)患者合并结核分枝杆菌(Mycobacterium tuberculosis,MTB)或非结核分枝杆菌(non-tuberculous mycobacteria,NTM)感染的免疫学特征及其对常用抗结核药物的耐药特点,为临床AIDS患者并发MTB或NTM感染的诊断和治疗提供参考。方法：选取2017年1月—2022年12月苏州市第五人民医院收治的44例AIDS合并MTB感染患者(设为AIDS/MTB感染组)和44例AIDS合并NTM感染患者(设为AIDS/NTB感染组)作为研究对象,采集患者的年龄、性别、免疫学检查结果,以及MTB和NTB对常用抗结核药物的药敏试验结果等信息,分析AIDS患者合并MTB或NTM感染的免疫学特征与耐药特点。结果：AIDS/MTB感染组和AIDS/NTB感染组患者的性别均以男性为主(93.18%vs97.73%),而年龄上均主要集中在30～<50岁(56.82%vs 59.09%),但2组患者在性别和年龄上的分布情况经比较其差异无统计学意义(P&...     

非结核分枝杆菌病的治疗研究进展

非结核分枝杆菌病系由结核分枝杆菌复合群和麻风分枝杆菌以外的分枝杆菌(Non-tuberculous mycobacteria,NTM) 引起的疾病。NTM除引起肺部病变外,尚可引起其他部位病变,常见的是淋巴结炎、皮肤软组织感染和骨骼系统病变,对严重的细胞免疫抑制者还可引起血源性播散。由于多数传统抗结核药物对大多数NTM很少或没有活性,所以NTM病治疗困难,预后不佳。近十余年来对NTM病的研究已取得很大进展,药物研究亦在迅速进展中。在原有抗结核药物的基础上,又出现了一些抗结核新药,其中一些对NTM病有效。尤其近年研究的疏水衍生物,显示了更大的抗NTM活性。     

抗分枝杆菌植物天然产物研究进展

由分枝杆菌引起的感染是人类健康的巨大威胁。目前,多种结核分枝杆菌和非结核分枝杆菌对临床抗分枝杆菌药物具有较高的耐药性。中药治疗分枝杆菌感染具有悠久历史。例如,中药材狼毒已应用于抗结核分枝杆菌的治疗。非中药来源的植物中,也蕴含丰富的抗分枝杆菌成分。这些植物来源的天然产物具有较好的结构多样性,是开发抗分枝杆菌药物的潜在来源。本文综述了近年来在中药和其他非中药来源植物中发现的,具有良好抗分枝杆菌活性的化合物或提取物,并介绍了它们的作用机制。这些活性植物天然产物为新抗分枝杆菌药物的发现提供了化合物库。同时,这些植物天然产物结构与现有抗分枝杆菌药物具有显著的差别,研究其作用机制,也可发现新的抗分枝杆菌靶标。     

40例非结核分支杆菌肺病的临床分析

目的了解非结核分支杆菌(NTM)肺病对一线抗痨药物的耐药情况,探讨NTM肺病反复发作的原因。方法在本研究所2003-2008年间876例分支杆菌培养阳性的病例中,经鉴定确诊为NTM肺病的资料完整的40例病例进行回顾性分析。结果40例患者中多数对一线抗痨药物(异胭肼,利福平,链霉素)耐药,而对乙胺丁醇的敏感性较好:40例患者中既往"肺结核"病史较长,平均6年,最长达15年:平均治疗次数1.86次,最长达6次。结论对于分支杆菌培养阳性的患者应及早做菌种鉴定,一经确诊应做多种药物的敏感试验,选择最佳联合治疗方案,并坚持全程化疗。     

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.     

靶向共价键药物的研究进展

药物与靶标的结合是启动药理作用的本源,共价键药物是以共享电子的方式来实现与靶标的结合,其中大多为抗感染、抗肿瘤以及心脑血管、神经系统和代谢类药物。简介共价键药物与非共价键药物的区别以及既往的重磅级共价键药物与靶标的结合特点,分类综述靶向共价键药物的理性设计及与靶标的结合反应。     

Case report: cutaneous nontuberculous mycobacterial abscesses associated with insulin injections

Nontuberculous mycobacterial (NTM) infections are on the rise and often cause skin diseases that are misdiagnosed. The authors present three cases of atypical mycobacterial infections in insulin-dependent diabetics occurring in sites of subcutaneous insulin injections. One of the patients was vitamin D deficient at the time of infection with NTM. The history and clinical presentation of the cases are presented; pathogenesis and treatment are discussed in conjunction with the correlation of mycobacterial disease susceptibility with vitamin D deficiency.     

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。     

New therapeutic approaches targeted at the late stages of the HIV-1 replication cycle

Owing to the serious clinical consequences associated with acquisition of resistance to current antiretroviral drugs, discovery of new drug targets and development of novel anti-HIV-1 therapeutic agents have become a high research priority. The late stages of HIV-1 replication involve the processes of assembly, budding and maturation, and comprise several new potential therapeutic targets which have not (yet) been targeted by any of the antiretroviral drugs approved at present. The structural protein Gag plays a central role in these stages through its different regions and mature Gag proteins working in concert. In this article, we highlight a number of steps in the late stages of HIV-1 replication that represent promising targets for drug discovery. Recent progress in development of related inhibitors targeting at CA, zinc fingers of NC, p6-Tsg101 interaction, lipid rafts of plasma membrane, proteolytic cleavage sites in Gag and gp160 processing is also reviewed.     

Molecular approaches to target discovery:--evaluating targets for anti-tuberculosis drug discovery programmes

Selection of appropriate targets for launching antituberculosis drug discovery programmes is challenging. This challenge is magnified by the limited repertoire of 'validated targets' and the paucity of clinically successful drugs. However, continued understanding of the biology of the microbe and its interaction with the host has enabled detailed evaluation of several interesting pathways and novel targets. The value of a target that is suitable for antituberculosis drug discovery needs to be defined not only in the context of its 'essentiality' for survival in vitro but also against a variety of properties relevant to activities in the drug discovery process, e.g.; selectivity, vulnerability, suitability for structural studies, ability to monitor inhibition in whole cells etc. It is also rarely feasible to obtain all the relevant information on the target prior to the launch of a discovery programme. Thus, there is a continuous confidence-building exercise on the validity of a target. Several novel approaches have enabled exploitation of the mycobacterial genome and prioritisation of putative targets; the concept of 'sterilisation' is now being evaluated not only through the availability of structurally diverse probe compounds but also by the ability to characterise metabolic pathways in vivo. The impact of the current knowledge base on the different facets of 'target validation' relevant to antituberculosis drug discovery is discussed in this article with emphasis on developing appropriate matrix systems to prioritise them. The article also discusses the influence of lead generation approaches with specific reference to antibacterial drug discovery.