921株结核分枝杆菌耐药性分析

目的:调查结核分枝杆菌的耐药情况,为临床合理用药提供依据。方法:对921例肺结核患者进行结核分枝杆菌培养和药敏试验。结果:单耐药的耐药率由高到低依次是链霉素(18.3%)、异烟肼(14.6%)、利福平(13.1%)、乙胺丁醇(5.3%),耐多药的耐药率为3.3%。19～39岁年龄段无论是单耐药率还是耐多药率都较高,而<18岁年龄段的耐药率最低。结论:结核分枝杆菌的耐药形势比较严峻。     

雾化吸入治疗耐多药肺结核

目的　探讨用雾化吸入治疗耐多药肺结核的治疗价值。方法　将 72例耐多药肺结核患者随机分为治疗组和对照组。治疗组强化期采用雾化吸入加化疗 ,对照组只加化疗。结果　强化期结束时 ,经雾化吸入治疗组症状明显改善者 90 .6% ,痰菌阴转率 87.5 % ,病灶显著吸收率 87.5 % ;明显高于单纯化疗组的 5 6.3 % ,5 0 .0 % ,3 7.5 % (P <0 .0 5 )。结论　用雾化吸入治疗耐多药肺结核疗效显著 ,且无并发症及明显毒付反应     

Molecular Characterization of Drug-Resistant Beijing Family Isolates of Mycobacterium Tuberculosis from Tianjin,China

Objective Tuberculosis remains a severe public health issue, and the Beijing family of mycobacterium tuberculosis （M. tuberculosis） is widespread in East Asia, especially in some areas in China, like Beijing and Tianjin. This study aimed at determining the mutation patterns of drug-resistant Beijing strains of M. tuberculosis isolated from Tianjin, China. Methods A total of 822 M. tuberculosis isolates were screened for drug resistance by an absolute concentration method and the genotype was identified by PCR. 169 drug-resistant isolates of the Beijing family were analyzed for the potential mutations in the rpoB, katG, inhA promoter region and in rpsL, rrs and embB genes, which are associated with resistance to rifampin （RFP）, isoniazid （INH）, streptomycin （SM） and ethambutol （EMB） respectively by PCR and DNA sequencing. Results Fifty-eight out of 63 RFP-resistant isolates were found to carry the mutations within the 81-bp RFP resistance determining region （RRDR） of the rpoB gene and the most frequent mutations occurred at codon 531 （44.4%）, 526 （28.6%）, and 516 （7.9%） respectively. 16 mutation pattems affecting 12 different codons around the RRDR of rpoB were found. Of 116 INH-resistant isolates, 56 （48.3%） had the mutation of katG 315 （AGC→ACC） （Ser→Thr）, 3 （2.6%） carried S315N （AGC→AAC） and 27 （16.0%） had the mutation of inhA-15A→T. 84 out of 122 SM-resistant isolates （68.9%） displayed mutations at the codons 43 or 88 with AAG→AGG （Lys→Arg） of the rpsL gene and 22 （18.0%） with the mutations at positions 513A→C, 516C→T or 905 A→G in the rrs gene. Of 34 EMB-resistant isolates, 6 had mutation with M306V （ATG→GTG）, 3 with M306I （ATG→ATT）, 1 with M306I （ATG→ATA）, 1 with D328Y （GAT→TAT）, 1 with V348L （GTC→CTC）, and 1 with G406S （GGC→AGC） in the embB gene. Conelusion These novel findings extended our understanding of resistance-related mutations in the Beijing strains of M. tuberculosis and may provide a scientific basis for development of new strategies for diagnosis and control of tuberculosis in China and other countries where Beijing strains are prevalent.     

四川和安徽两省结核耐药危险因素分析

目的 了解四川和安徽两省继发性耐药结核患者产生的主要社会行为危险因素,为预防耐药性结核病的发生提供依据.方法 选取四川和安徽两省结核病防治所就诊的结核患者1489例,四川875例,安徽省614例.其中继发耐药结核患者356例.采用问卷调查患者可能导致继发性耐药结核的主要社会行为危险因素,并对其危险因素进行logistic回归分析.结论 四川和安徽两省继发耐药结核产生的主要社会危险因素为患者治疗时间长、督导化疗不彻底、患者治疗中依从性差、药品供应不满意、流动人口、治疗过程中有中断和治疗过程中经常饮酒.其比值比及可信区间分别为10.279(6.842～17.663)、 9.880(6.743～16.672)、 4.683(1.935～9.523)、3.859(1.584～9.218)、5.030(2.683～10.891)、4.938(2.162～9.982)和2.338(1.084～7.116).结论 加强对继发性耐药的社会行为危险因素的预防干预,对减少耐药结核的产生具有重要的意义.     

结核分枝杆菌(MTB)异质性耐药研究进展

 异质性耐药,是指在同一样本中同时存在耐药菌和敏感菌的现象,这体现了细菌群体从部分耐药向完全耐药转变的过程。研究异质性耐药对于认识耐药结核病的发展过程,以及评估治疗方案和指导临床用药具有重要的意义。本文对结核分枝杆菌(Mycobacterium tuberculosis,MTB)异质性耐药的产生及其对临床的影响进行了综述。     

左氧氟沙星联合卷曲霉素化疗方案治疗耐多药肺结核疗效分析

目的：分析左氧氟沙星联合卷曲霉素化疗方案治疗耐多药肺结核的临床疗效。方法整群选取2014年11月—2015年11月该院收治的89例耐多药肺结核患者为该次研究对象,随机分为两组,对照组44例和治疗组45例。两组患者均使用常规药物进行治疗,治疗组在常规药物基础上给予左氧氟沙星联合卷曲霉素进行治疗,对照组在常规药物基础上给予乙胺丁醇联合链霉素进行治疗。观察两组临床疗效。结果治疗后,对照组患者中痰菌为阴性23例（52.3%）,治疗组为37例（82.2%）,两组患者痰菌阴转率比较,差异有统计学意义（P<0.05）。结论左氧氟沙星联合卷曲霉素化疗方案治疗耐多药肺结核效果显著,提高了痰菌阴转率,病灶吸收情况较好,值得临床应用。     

利福布汀联合多种药物长效治疗耐多药肺结核的有效性分析

目的：分析利福布汀联合多种药物长效治疗耐多药肺结核的有效性。方法方便选取该院2013年7月—2014年7月收治的90例耐多药肺结核患者,随机分为两组,各45例。两组患者均给予丙硫异烟胺、乙胺丁醇、左氧氟沙星等药物进行基础治疗,研究组与对照组在此基础上分别采用利福布汀与利福喷丁治疗。比较两组病灶吸收率及不良反应发生率。结果研究组病灶吸收率与不良反应发生率分别为71.1%、22.2%,对照组分别为68.9%、20.0%,对比两组病灶吸收率与不良反应发生率差异无统计学意义(P>0.05)。结论给予耐多药肺结核患者利福布汀联合多种药物进行治疗,其疗效与利福喷丁基本一致,具有较好的长效治疗机制。     

1800株结核分枝杆菌对10种抗结核药物耐药分析

目的:了解住院结核患者常用10种抗结核药物的耐药趋势。方法:以南京市胸科医院2001年至2006年的培养阳性结核分枝杆菌为本次研究对象,用绝对浓度法做RFP、INH、SM、EMB、DP、OFLX、PAS、KM、TH1321和CPM10种药物的药敏试验。结果:共有耐药菌株1800例,总耐药率70%,耐多药率为54.9%。结论:结核分枝杆菌对多种药物的耐药性有差异。该院结核分枝杆菌对部分药物的耐药性流行水平有上升趋势,获得了该院耐药性水平资料,对临床用药具有重要的必要性和指导性。     

初治培阳肺结核患者起始耐药情况分析

目的了解肺结核患者结核分枝杆菌起始耐药情况,制定科学的防治对策。方法采用世界卫生组织制定的结核分枝杆菌耐药监测方案进行结核分枝杆菌耐药监测。使用绝对浓度法对山东省胸科医院住院的1184例培阳肺结核患者的耐药性进行测定。结果 1184例培阳肺结核患者中,全敏感834例(70.44%),耐药350例(29.56%)。其中起始耐药157例(44.86%),复治耐药193例(55.14%)。在起始耐药病例中,单耐药结核病(MonoDR-TB)53例(33.8%),其中耐链霉素的病例最多(38例,24.2%);多耐药结核病(PDR-TB)72例(45.9%);耐多药结核病(MDR-TB)20例(12.7%);广泛耐药结核病(XDR-TB)12例(7.6%);无全耐药结核病(TDR-TB)患者。结论山东省胸科医院住院肺结核患者结核分枝杆菌起始耐药现状十分严重。实现抗结核防治方案的统一管理、全程督导化疗势在必行。     

心理护理干预在耐多药结核病患者中的效果探讨

目的：探讨心理护理干预在耐多药结核病患者中的效果。方法将2001年1月—2014年10月期间,该院收治的耐多药肺结核患者120例作为研究对象,采用对照研究,将患者随机分为对照组（60例）和心理护理干预组（60例）,对照组采用一般的护理方法,心理护理干预组则在一般护理的基础上,实施心理护理干预,包括：①用尊重建立良好护患关系。②情绪干预。③认知干预。④行为干预。⑤社会及家庭支持干预。比较两组患者的治疗效果、满意度以及住院期间焦虑状况,探讨个性化护理干预方法的临床应用价值。结果心理护理干预组的显吸率、吸收率以及病灶吸收总有效率明显高于对照组,差别有统计学意义（P<0.05）;心理护理干预组的满意度明显高于对照组,差异有统计学意义（P<0.05）;心理护理干预组患者的焦虑状况明显优于对照组,差异有统计学意义（P<0.05）。结论实施心理护理干预有助于改善患者病情,提高护理满意度,减轻患者焦虑状况,值得进一步推广应用。     

利血平对耐药结核分枝杆菌临床株的作用

目的 观察泵抑制剂(利血平)对耐药结核分枝杆菌临床分离株的作用.方法 应用3组BacT.ALERT3D培养仪系统的培养基,分别命名为A、B、C组培养基.3组培养基均接种42株耐药结核分枝杆菌临床分离株,其中A、B组同时加入利福平1 μg/mL;环丙沙星2 μg/mL.;利福平1 μg/mL和环丙沙星2 μg/mL;A、C组同时加入利血平20 mg/L;C组未加入任何抗结核药物.结果 在A组培养基中,耐利福平1μg/mL的14株菌株中有2株恢复对利福平的敏感性,12株仍然耐药;耐环丙沙星2μg/mL的6株菌株和耐利福平1μg/mL及环丙沙星2μg/mL的22株菌株全部恢复药物敏感性.在B组培养基中,42株耐药结核分枝杆菌临床分离株,药物耐药性无变化.在C组培养基中,42株耐药结核分枝杆菌临床分离株明显生长,说明利血平对所研究菌株无抑制作用.A组与B组培养基细菌的药物敏感性差异有统计学意义(P＜0.01).结论 结核分枝杆菌存在耐药机制之一的外排系统;泵抑制剂之一利血平对耐药的结核分枝杆菌临床分离株有抑制其外排作用,使结核分枝杆菌恢复敏感性.     

结核分枝杆菌耐药性分析

目的:回顾性分析结核分枝杆菌耐药状况。方法:分析分离培养出并使用噻吩-2羧基肼(TCH)和对硝基苯甲酸(PNB)进行分型确认的127株结核分枝杆菌药物敏感试验结果,包括异烟肼(H)、利福平(R)、链霉素(S)、乙胺丁醇(E)、吡嗪酰胺(Z)、力克肺疾(D)、氧氟沙星(O)、丙硫乙烟胺(TH)、卷曲霉素(C)、对氨基水杨酸钠(P)、丁胺卡那(AK)。11种药物采用绝对浓度法进行药物敏感性检测。结果:127株结核分枝杆菌中,R耐药率最高,高浓度药物耐药达74%、C耐药率最低,高浓度药物耐药率为3.9%;HR联合耐药率为67.7%,HRS联合耐药率为52%,CThZ联合耐药率为9.4%,同时对7种药物耐药的耐药率为39.4%,同时对11种药物的耐药率为11%。结论:结核分枝杆菌耐药情况已很严重,需要更严格的执行结核病预防和治疗。     

耐多药肺结核的肺切除术

为探讨肺切除术治疗耐多药肺结核的重要性,对３８ 例耐多药肺结核实施不同术式肺切除术,并进行抗结核治疗。所有病例痰菌均转阴,无支气管胸膜瘘、脓胸等并发症。结果表明肺切除术是治疗耐多药肺结核的重要方法。     

Prevalence and outcome of isoniazid-monoresistant tuberculosis at a university hospital in Saudi Arabia

Objectives:To determine the prevalence and outcome in patients with isoniazid-monoresistant Mycobacterium tuberculosis complex and compare them to those in patients with non-isoniazid-monoresistant Mycobacterium tuberculosis.Methods:This cross-sectional analytical study was conducted at King Khalid University Hospital, Riyadh, Saudi Arabia. The data were retrospectively collected from the electronic medical records of patients who tested positive for Mycobacterium tuberculosis between May 2015 and April 2019.Results:We identified 105 patients infected with Mycobacterium tuberculosis. The prevalence proportion of isoniazid-monoresistant tuberculosis was 8.6% (n=9). Five patients with isoniazid-monoresistant tuberculosis (55.6%) were successfully treated, while one patient died. In the nonresistant population, 51 (53.1%) patients were successfully treated. However, 12 (12.5%) patients with no isoniazid resistance had an unsuccessful treatment outcome. The resistant group had a longer treatment duration with a mean of 12 months compared to the non-isoniazid-resistant group, with a mean treatment duration of 9.5 months. Twenty-eight patients (26.7%) had adverse events, with the majority of them being in the non-isoniazid-resistant group.Conclusion:Isoniazid monoresistance is the most common form of drug resistance found in our population. Our study has not shown any significance in the outcome of isoniazid-resistant cases compared to non-isoniazid-resistant cases. This may be due to the low number of isoniazid-monoresistant cases in our population.     

Resistance to Antituberculosis Drugs in Pulmonary Tuberculosis

Background

Incidence of drug resistance and pattern of susceptibility to antitubercular drugs in pulmonary tuberculosis amongst soldiers and their families was studied for four years at a military hospital in northwest India.

Methods

Identification and susceptibility tests were carried out as per procedures laid out in laboratory manual of Tuberculosis Research Centre (TRC), Chennai.

Results

Of the 172 strains of Mycobacterium tuberculosis (MTB) isolated from sputum samples, 150 (87.21%) were sensitive and 22 (12.79%) showed resistance to one or more antitubercular drugs. Acquired drug resistance was observed in 7 (31.82%) and primary drug resistance in 15 (68.18%) cases. Among 22 drug resistant cases, who were on short course chemotherapy (SCC), resistance to single drug was observed in 12 (54.54%), two drugs in 7 (31.82%) and to three or more drugs in 3 (13.64%) isolates. Fourteen (18.14%) strains were resistant to Streptomycin, 8 (4.65%) to Rifampicin, 11 (6.40%) to Isoniazid, 1 (0.58%) to Pyrazinamide and 2 (1.16%) to Ethambutol. Multidrug resistance was observed in 5 (2.91%) cases, of which resistance to Isoniazid and Rifampicin was present in 2 (1.16%) and their combination with other drugs in other 3 (1.74%) isolates.

Conclusions

Drug susceptibility pattern to antitubercular drugs is discussed and compared with studies from other centres.Key Words: Drug resistance, Antitubercular drugs, Mycobacterium tuberculosis     

Molecular characteristics of rifampin and isoniazid resistant Mycobacterium tuberculosis strains from Beijing, China

Background China is one of the high burden countries of Mycobacterium tuberculosis （TB） infection globally, with high incidence and mortality. We studied the molecular characteristics of rifampin （RIF） and isoniazid （INH） resistant Mycobacterium tuberculosis strains from Beijing, China, in order to find out the genetic marker for rapid detection of specific drug resistance. Methods Forty pansusceptible and 81 resistant strains of Mycobacterium tuberculosis isolated from Beijing, China during 2002-2005 were analyzed. The modified rifampin oligonucleotide （RIFO） assay based on reverse line blot hybridization was used to detect mutations in the 81 bp hot-spot region of rpoB gene, which is associated with RIF resistance. The INH resistance associated genes, regulatory region mab-inhA （-15C/T） and structural gene katG S315T were detected by reverse line blot hybridization and PCR-restriction fragment length polymorphism （RFLP） method respectively. All the strains were typed by spoligotying and the Beijing genotype was further subdivided by NTF locus analysis. The distribution of drug resistance associated mutations in the above genes was compared in these groups. Results Sixty-five （91.5%） of 71 RIF resistant and 52 （92.9%） of 56 multidrug-resistant （MDR, i.e. resistant to at least RIF and INH） strains were found to harbor mutations in the rpoB hot-spot region. No mutation was detected in RIF sensitive strains. The specificity and sensitivity of the modified RIFO assay were 100% and 91.5%, respectively, katG315 AGC〉ACC and inhA-15C〉T mutations were found in 40 （60.6%） and 10 （15.2%） of 66 INH resistant strains, respectively; 7.6% of INH-resistant strains had mutations in both of these genes. Therefore, a combined use of both katG315 and inhA-15 identified 68.2% of INH-resistant strains. The Beijing genotype accounted for 91.7% of total strains and was further subdivided into ＂modern＂ （76.6%） and ＂ancestral＂ （23.4%） group. There is no significant difference between ＂ancestral＂ and ＂modern＂ group in prevalance of drug resistance-associated gene mutations. Conclusions The hot-spot region of rpoB gene can be used as genetic marker for detection of RIF resistant strains; a combined use of both katG315 and inhA-15 can improve the detection rate of I NH resistant strains; the Beijing genotype is prevalent in Beijing, China; the modified RIFO assay can be a practical tool for rapid detection of RIF resistant and MDR isolates in the routine diagnostic work.     

苏北农村结核分枝杆菌临床分离株耐药特征分析

目的分析苏北农村结核分枝杆菌临床分离株的耐药现状和特点,为结核病防制提供依据。方法应用间接比例法药敏试验测定苏北两县2001年结核病人的初始分离株对异胭肼(INH)、利福平(RIF)、乙胺丁醇(EMB)和链霉素(STR)的敏感性。结果152株临床分离株的总耐药率为32.9%,初始耐药率和获得性耐药率分别为28.6%和48.5%;耐多药率为17.1%,初始和获得性耐多药率分别为16.0%和21.2%。同时耐INH和STR是最常见的耐两药或多药类型,其次是耐INH和RIF。四种抗结核药物的耐药率依次为INH(26.3%)、STR(24.3%)、RIF(18.4%)、EMB(10.5%)。RIF耐药株中,92.9%的同时耐INH。结论当地农村结核病耐药水平较高,耐药性的发生趋向于对多种药物同时耐药,RIF耐药可作为耐多药的标志。     

巴豆油抗多重耐药结核分枝杆菌作用实验研究

目的：观察巴豆油体外对耐药结核杆菌的生长抑制作用。方法：在用分离培养的耐利福平(RFP)、雷米封(INH)二重耐药菌株，分别接种于含有不同浓度巴豆油以及含INH、RFP的豆漫液结核分枝杆菌对照培养基，观察各组结核分枝杆菌的生长情况。结果：在含INH、RFP的对照组培养基上，菌落生长正常，高浓度巴豆油组(1：10～1：160)对结核菌生长有抑制作用，到培养终止期(第40d)仍无细菌生长。将低浓度巴豆油组(1：1280)缓慢生长的菌落反复接种到1：80～1：1280的巴豆油培养基，接种5代后未发现耐巴豆油菌株。结论：1：160以上浓度的巴豆油培养基有体外抗耐药结核菌的作用，并且没有诱导耐药菌株的产生。     

PCR-SSCP检测耐多药结核菌基因与细菌培养结果对比分析

目的应用PCR-SSCP检测常规及BACTEC培养耐INH、RFP、SM的耐多药结核分枝杆菌临床分离株KatG、rpoB、rpsL基因突变,分析其敏感性和特异性,评价其在检测结核分枝杆菌耐药性方面的价值和临床实用性。方法22株常规培养和8株BACTEC培养检出的高浓度及低浓度耐INH、RFP、SM耐多药结核分枝杆菌分离株,分别用PCR-SSCP检测KatG、rpoB、rpsL基因,观察其电泳条带,并与结核菌标准株H37RV对比。结果22株常规培养耐INH、RFP、SM的耐多药结核分枝杆菌分离株中,KatG、rpoB、rpsLPCR扩增产物,用SSCP分别检出KatG基因16株(72.7%)、rpoB基因19株(86.4%)和rpsL基因14株(63.6%)。8株BACTEC培养耐INH、RFP、SM的耐多药结核分枝杆菌分离株中分别检出KatG基因5株(62.5%),rpoB基因6株(75%)、rpsL基因5株(62.5%)。综合两者KatG、rpoB和rpsL基因检出率分别为70.0%(21/30)、83.3%(25/30)和63.3%(19/30)。高浓度耐药与低浓度耐药分离株中的检出率有显著差异(P<0.05),常规培养与BACTEC培养分离株中的检出率无显著差异(P>0.05),与结核菌标准株H37RV电泳条带对比,特异性为100%,敏感性97%。结论PCR-SSCP敏感、特异,可快速检测结核分枝杆菌的KatG、rpoB和rpsL基因,可用于耐多药结核分枝杆菌的临床检测。     

住院肺结核病人耐药状况与疗效分析

目的　了解结核病医院中住院病人的耐药及多耐药结核病 ( MDR-TB)流行情况、特点及影响因素。方法　用临床流行病学方法进行统计和分析。结果　耐药率为 3 0 .71 % ,MDR-TB发病率为1 1 .68% ,初始 MDR-TB为 2 .55% ,继发 MDR-TB为 9.1 3 % ,MDR-TB死亡率为 9.4 8%。结论　耐药及MDR-TB发病率逐年增加 ,高死亡率。