菌阴肺结核患者痰标本中结核分枝杆菌rpoB耐药基因突变的检测

目的应用套式PCR-DNA测序方法直接检测菌阴肺结核患者痰标本中结核分枝杆菌相关的rpoB基因突变,以期建立一种判定菌阴肺结核患者是否对利福平有无耐药性的方法。方法采用套式PCR-DNA测序方法直接检测112例活动性肺结核患者和20例非结核性肺部疾病患者痰标本中结核分枝杆菌rpoB基因突变情况。同份痰标本同时做涂片抗酸染色、罗氏培养。结果112例活动性肺结核患者痰标本39例为菌阴(涂阴培阴),39例菌阴痰中套式PCR扩增18例呈阳性,产物DNA测序2例有rpoB基因突变,位点为第526发生了CAC→GAC突变和第531发生了TCG→TTG突变。20例非结核性肺部疾病患者标本套式PCR扩增均为阴性,特异性100%。结论套式PCR-DNA测序可望为直接检测菌阴肺结核患者临床痰标本中结核分枝杆菌耐利福平的准确、特异、快速的方法。     

探针熔解曲线法快速检测结核分枝杆菌利福平、异烟肼、乙胺丁醇及链霉素耐药突变

目的评价探针熔解曲线法检测结核分枝杆菌利福平(RIF)、异烟肼(INH)、乙胺丁醇(EMB)及链霉素(SM)耐药突变的方法学应用价值。方法用PCR探针熔解曲线法检测110株结核分枝杆菌临床分离株RIF、INH、EMB及SM耐药突变情况,以传统的比例法药物敏感性试验检测结果为标准,评价探针熔解曲线法的敏感性、特异性和一致率,并应用测序方法分析结果不一致菌株的耐药突变位点。结果以比例法检测结果为标准,熔解曲线法检测RIF耐药的敏感性为98.51%,特异性为95.35%,诊断符合率为97.27%;检测INH耐药的敏感性为94.12%,特异性为95.24%,诊断符合率为94.55%;检测EMB耐药的敏感性为88.64%(39/44),特异性为75.76%(50/66),诊断符合率为80.91%(89/110);检测SM耐药的敏感性为82.98%,特异性为80.95%,诊断符合率为81.82%。两种检测方法结果不符菌株的测序结果大部分与熔解曲线法的检测结果一致。结论探针熔解曲线分析法检测速度快,敏感性高,特异性强,可用于结核分枝杆菌耐药突变的快速检测。     

显色法芯片检测结核分枝杆菌利福平与异烟肼耐药基因的临床应用

目的观察离心柱法抽提、显色法芯片检测结核分枝杆菌(MTB)利福平(RIF)与异烟肼(INH)耐药基因的临床应用价值。方法离心柱法直接抽提痰液中MTBDNA,显色法芯片检测69例结核患者、30例非结核患者痰液和H37Rv标准MTB株DNArpoB、katG、inhA和ahpC4个基因片段多态性。结果42例RIF耐药组rpoB区基因总突变率为90.4%,rpoB511、513、516、526、531位点突变率分别为9.5%、9.5%、7.1%、40.4%、38.0%,有1例未检出芯片信号;46例INH耐药组katG、inhA、ahpC区域突变率分别为58.6%、19.5%、6.5%,有4例未检出芯片信号;30例非结核病人痰液芯片检测结果均为阴性,H37Rv标准株为野生型。结论离心柱法抽提、显色法芯片检测结核分枝杆菌RIF和INH耐药基因方法灵敏、特异、简便,无需特殊仪器,对指导临床用药价值较大。     

利福平注射液治疗初治菌阳肺结核病人的临床观察

目的评价化疗并用利福平注射液与利福平胶囊治疗初治菌阳肺结核的疗效。方法将80例初治菌阳肺结核患者随机分为2组,治疗组（40例）、对照组（40例）强化期分别用HZE加利福平注射液和HEZ加利福平胶囊方案治疗;观察强化期1、2个月末痰菌阴转、肺部病灶吸收及毒副反应情况。结果1、2个月末痰菌阴转率：治疗组分别为82．5％和97．5％,对照组分别为65．0％和85．0％;胸部X线改善显效率：治疗组分别为17．5％和40．0％,对照组分别为10．0％和25．0％;空洞闭合缩小率：分别为41．7％和22．7％。毒副反应：治疗组和对照组肝功能损害发生率分别为22．1％和25．2％,胃肠反应发生率分别为20．0％和45．0％。结论利福平注射液起效快、效果佳、副反应少,在控制症状、缩短排菌时间、降低传染性、减少副反应及抢救重症结核上有很好的效果,值得临床推广。     

Improved cough- and sputum-related quality of life after initiation of treatment in pulmonary tuberculosis

BackgroundCough and sputum are the major symptoms of pulmonary tuberculosis (TB). However, the relationship between these symptoms and treatment for TB is not fully understood. The aim of this prospective study was to clarify the cough- and sputum-related quality of life (QOL) in patients with pulmonary TB before and after initiation of treatment.MethodsThe study included 85 patients with active pulmonary TB who were hospitalized from July 2014 to August 2015. They completed the Leicester Cough Questionnaire (LCQ: range 3–21, the higher the better) and the Cough and Sputum Assessment Questionnaire (CASA-Q: range 0–100, the higher the better) on admission and at discharge after 2 months of treatment.ResultsThe LCQ and CASA-Q scores were reduced on admission. A multivariate linear regression analysis revealed that younger age, more than two cavitary lesions, and the presence of bronchial TB were associated with reduced LCQ total score. However, each score significantly improved at discharge, regardless of the initial grade of the sputum smear, site of the lesion, number of cavitary lesions, and presence of bronchial TB. The change in the mean LCQ total score was 2.28 (95% confidence interval, 1.56–3.00). The changes in the mean CASA-Q cough symptoms, cough impact, sputum symptoms, and sputum impact scores were 22.84 (18.44–27.25), 10.96 (7.20–14.71), 17.25 (13.33–21.18), and 5.25 (2.49–8.00), respectively.ConclusionsCough- and sputum-related QOL was impaired in patients with pulmonary TB before treatment but improved after initiation of treatment regardless of the clinical characteristics.     

脓肿分枝杆菌耐利福平机制的研究

目的 探讨脓肿分枝杆菌耐利福平的机制。方法 采用棋盘微量稀释法,分别测定利福平在加入不同浓度的改变细胞壁通透性的试剂和主动外排泵抑制剂时对脓肿分枝杆菌的最低抑菌浓度。通过利福平对脓肿分枝杆菌的最低抑菌浓度的变化情况来分析细胞壁通透性和主动外排在脓肿分枝杆菌耐利福平机制中的作用。结果 随着TWEEN-80、Trixon X-100、甲苯、乙醚、CCCP、利血平和泮托拉唑浓度的增加,利福平对脓肿分枝杆菌的最低抑菌浓度逐渐降低。对于TWEEN-80、Trixon X-100、CCCP和泮托拉唑,利福平对脓肿分枝杆菌的最低抑菌浓度由512 μg/mL降至小于32 μg/mL,0.1%的TWEEN-80、0.006 25%的Trixon X-100、0.1 μg/mL的CCCP和32 μg/mL的泮托拉唑为最适浓度;对于甲苯、乙醚和利血平,利福平对脓肿分枝杆菌的最低抑菌浓度由512 μg/mL降至64 μg/mL,0.25%的甲苯、0.25%的乙醚和8 μg/mL的利血平为最适浓度。它们均能促进利福平对脓肿分枝杆菌的抑菌作用。结论 细胞壁通透性和主动外排在脓肿分枝杆菌耐利福平的机制中有重要作用。     

利福平在体内对大鼠着床前胚泡的遗传和发育毒性

利福平在体内对大鼠着床前胚泡的遗传和发育毒性１楼宜嘉王立明周建设张丽进（浙江医科大学药学系药理学教研室，杭州３１０００６）利福平（ｒｉｆａｍｐｉｎ，Ｒｉｆ）为药酶诱导剂，患结核病的育龄妇女如在口服避孕药的同时服用Ｒｉｆ可加速前者的灭活，增加怀孕的可能...     

Treatment of latent tuberculosis infection: An update

Isoniazid (INH) has been the mainstay of treatment of latent tuberculosis infection for almost 50 years. The currently recommended preferred regimen is 9 months daily self‐administered INH (9H); this has efficacy of more than 90% if completed properly. Unfortunately, INH is associated with serious adverse events, including hepatotoxicity. Although risk factors for this complication are well established, allowing for better selection of candidates for therapy, this complication still occurs, and is occasionally fatal. Hence close follow up of patients is necessary, increasing the cost and complexity of treatment. This problem, plus the lengthy duration, results in poor acceptance by patients and providers, and poor adherence by patients. As a result, many preventable cases of tuberculosis continue to occur, and the public health impact of latent tuberculosis infection treatment is suboptimal. These problems have spurred interest in finding shorter, safer and cheaper alternative regimens, with similar efficacy. Of the many regimens that have been examined, 2 months of rifampin and pyrazinamide has excellent efficacy—in experimental studies in mice and randomized trials, largely in HIV‐infected persons. However, while the safety of 2 months of rifampin and pyrazinamide appears acceptable in HIV‐infected persons and children, in non‐HIV‐infected adults this regimen is associated with an unacceptably high rate of severe liver toxicity. Three to four months of INH and rifampin has had equivalent effectiveness as 6 months INH in several randomized trials. However, completion of therapy and toxicity has been the same as with INH—possibly because two drugs are taken rather than one. The fourth commonly studied regimen is 4 months rifampin. This has been found to have significantly better completion than 9H, with significantly less toxicity, especially hepatotoxicity. However, only one trial has evaluated efficacy and effectiveness of mono‐rifampin therapy. In this trial, 3 months rifampin had somewhat better efficacy than either 3 months of isoniazid and rifampin (3HR) or 6 months isoniazid. Two large scale trials are ongoing; one is comparing efficacy and effectiveness of 9H with 4 months rifampin (both daily and self‐administered), while the second, which is nearing completion, compares daily self‐administered 9H with 3 months directly observed once weekly INH combined with rifapentine. The results of these two trials will likely shape future recommendations substantially.     

立复欣与利福平治疗渗出性结核性胸膜炎的临床观察

目的比较立复欣与利福平在治疗结核性渗出性胸膜炎中的临床效果和副作用. 方法选择确诊的结核性渗出性胸膜炎80例,随机分为立复欣研究组与利福平对照组进行回顾性分析,立复欣研究组40例,利福平对照组40例. 结果立复欣研究组结核性渗出性胸膜炎痊愈62.5%,好转35%,无效2.5%,利福平对照组结核性渗出性胸膜炎痊愈30%,好转50%,无效20%.两组总有效率分别是97.5%和80%,两组比较差异有显著性(P<0.05),立复欣在肝功能、血象影响方面与对照组差异无显著性.结论应用立复欣方案在治疗结核性渗出性胸膜炎中有较好的临床价值,经济条件好的地区或住院患者可考虑应用.