肺结核合并糖尿病对抗结核药物血药浓度的影响

目的 研究肺结核合并糖尿病对吡嗪酰胺、左氧氟沙星的血药峰浓度的影响,为糖尿病合并肺结核患者用药提供理论依据。方法 以随机数字表法选取糖尿病合并肺结核的患者为观察组（左氧氟沙星组30例,吡嗪酰胺组20例）,单纯肺结核为对照组（左氧氟沙星组30例,吡嗪酰胺组20例）,两组分别服用抗结核药物吡嗪酰胺、左氧氟沙星,在服药7 d后,用高效液相色谱法（HPLC）测定患者抗结核药物的血药峰浓度,两组间进行对比,采用SPSS 13.0软件进行统计分析。结果 左氧氟沙星在糖尿病合并肺结核组的血药峰浓度较单纯肺结核组明显升高［分别为（8.03±2.60）μg/ml和(6.66±1.76) μg/ml,t=2.39,P=0.02］;而吡嗪酰胺在两组间差异无统计学意义［分别为(14.24±4.79)μg/ml和(14.86±5.74)μg/ml,t=0.37,P=0.71］。结论 左氧氟沙星在糖尿病合并肺结核患者体内的血药峰浓度较单纯肺结核患者明显升高,提示糖尿病患者在应用左氧氟沙星时应该注意其血药峰浓度。有无糖尿病对吡嗪酰胺在体内血药浓度没有影响。     

抗结核药品合理化使用核查方法的探讨

目的 探讨药品使用核查的方法,间接评价药品使用的合理性。 方法 采取典型调查的方法,选择河南省（县1、县2）、重庆市（县3、县4）和吉林省（县5、县6）,共6个县作为调查现场,通过全国结核病防治季报表获得各结核病防治机构肺结核患者发现和治疗转归等信息,同时查阅各结核病防治机构药品出入库登记本和患者病历获得药品出入库数量、过期破损数量和断货天数等信息。根据指标定义计算缺货率、过期破损率、正确处方率和药品使用核查差异度（参考区间定为±25%）等指标。2007年1-12月,调查现场共发现新发涂阳肺结核患者2122例,复治涂阳肺结核患者202例,涂阴肺结核患者1596例。新发涂阳肺结核患者2个月末痰检未阴转率为6.03%（128/2122）;复治涂阳肺结核患者2个月末痰检未阴转率为7.92%（16/202）。 结果 调查现场缺货率为1.78%［234/（36×365）］,过期破损率为0.57%［2159/（125 544+250 440）］;按整群抽样调查的方法调查了1200例肺结核患者,均按照《中国结核病防治规划实施工作指南（2008年版）》的要求开出正确处方,正确处方率100%;HRZE板式组合药使用核查差异度为－41.93%［（84.378－119 760）/84.378］,最高为－12.1%［（13 140－14 730）/13 140］,最低为－86.36%［（10 673－19 890）/10 673］,其中县4、县5和县6差异度低于－25%;HR板式组合药使用核查差异度为－28.60%［（173 475－223 080）/173 475］,最高为－14.05%［（34 470－39 600）/34 470］,最低为－114.51%［（17 761－38 100）/17 761］,其中县5和县6差异度低于－25%;HRE板式组合药使用核查差异度为31.22%［（26 434－18 180）/26 434］,最高为90.91%［（3960－360）/3960］,最低为3.52%［（2985－2880）/2985）］,其中县1、县2和县5差异度高于25%。 结论 通过比较理论与实际消耗量差异的方法进行药品使用核查,可以粗略评价抗结核治疗中合理化用药的情况,建议每6个月或1年开展一次。     

Spectrum of Choroidal Involvement in Presumed Ocular Tuberculosis: Report from a Population with Low Endemic Setting for Tuberculosis

Objective: To describe the clinical spectrum and outcome of patients with presumed tubercular uveitis and choroidal involvement.

Methods: A retrospective case series nested in a cohort study was enrolled at a tertiary referral eye care center in the UK. Failure was defined as recurrence of lesion within 6 months of completion of antitubercular therapy (ATT) or corticosteroid therapy.

Results: Seventy-seven patients with presumed ocular tuberculosis and choroidal involvement were included in the study. Mean age was 45.5 ± 15.7 years, 44 (57.1%) patients were male, and 51 (66.2%) presented with bilateral disease. Choroidal granuloma was the most frequent clinical presentation (n = 27, 35.07%), followed by multifocal choroiditis (n = 24, 31.17%) and serpiginous-like choroiditis (n = 18, 23.38%). Quantiferon Gold in Tube Test (QFT) was positive in 64 (83.11%) patients. Fifty (64.94%) patients received ATT.

Conclusions: Choroidal involvement in presumed ocular tuberculosis can present with a variable spectrum. Treatment failure rates were equivalent between ATT and non-ATT treated groups.     

Synthetic investigational new drugs for the treatment of tuberculosis

Introduction: Tuberculosis (TB) is a major global health concern. And while there are treatments already on the market, there is a demand for new drugs that are effective and safe against Mycobacterium tuberculosis, which reduce the number of drugs and the duration of treatment in both drug-susceptible TB and multidrug-resistant TB (MDR-TB).

Area covered: This review covers promising novel investigational TB drugs that are currently under development. Specifically, the authors review the efficacy of novel agents for the treatment of TB in preclinical, phase I and phase II clinical trials. The authors also review the safety and tolerability profiles of these drugs.

Expert opinion: Bedaquiline and delamanid are the most promising novel drugs for the treatment of MDR-TB, each having high efficacy and tolerability. However, the best regimen for achieving better outcomes and reducing adverse drug reactions remains to be determined, with safety concerns regarding cardiac events due to QT prolongation still to be addressed. Pretomanid is a novel drug that potentially shortens the duration of treatment in both drug-susceptible and drug-resistant TB in combination with moxifloxacin and pyrazinamide. Linezolid shows marked efficacy in the treatment of MDR-TB and extensively drug-resistant TB (XDR-TB), but the drug is known to cause significant adverse drug reactions, including peripheral neuropathy, optic neuropathy and myelosuppression. These adverse reactions must be considered prior to prescribing long-term usage of this drug.     

结核分枝杆菌临床分离株药敏结果与耐药程度的关联分析

目的 探讨结核分枝杆菌临床分离株对12种抗结核药物的MIC值及其药敏检测结果 与耐药程度的关联规律,从而为临床制定治疗方案提供借鉴依据.方法 采用液体培养基联合MTT技术进行抗结核药物的MIC检测.对上海市肺科医院2009年1-6月间的163株结核分枝杆菌临床分离株进行RFP、INH、SM、EMB、OFLX、LVFX、MOX、AMK、CPM、PTA、CLA和PAIN的MIC检测和Bactec MGIT快速培养仪药敏检测,并进行MIC与耐药程度的关联性分析.结果 67%(42/62)的SM耐药株MIC≥16 μg/ml,63%(51/81)的INH耐药株MIC≥8 μg/ml,77%(50/65)的RFP耐药株MIC≥8 μg/ml,20%(12/60)的EMB耐药株MIC≥4 μg/ml;43%(25/58)的OFLX耐药株MIC≥8 μg/ml;41%(15/37)的AMK耐药菌株MIC≥16 μg/ml,41%(12/29)的CPM耐药菌株MIC≥4 μg/ml.OFLX耐药株的3个氟喹诺酮类药物的MIC(OFLX、LVFX和MOX的MIC分别为2～128、1～32和0.0625～1 μg/ml)差异有统计学意义(F=16.874,P<0.01);SM、INH、RFP、EMB、OFLX、AMK和CPM在任6种及7种药物同时耐药株中的MIC值(分别为0.5～128、2～64、0.25～128、1～32、1～64、0.5～128和1～128μg/ml)明显高于任1种及2种药物耐药菌株的MIC值(MIC值分别为0.25～128、0.0625～64、0.25～32、0.25～2、0.125～2、0.5～4和1～4 μg/ml,F值分别为20.066、40.499、47.197、70.373、91.432、41.840和21.547,P均<0.05);SM、INH、RFP、EMB在4种药物同时耐药菌株中MIC值(分别为1～128、2～64、0.25～128和1～32μg/ml)显著高于任1种及2种药物耐药株(MIC值分别为0.25～128、0.0625～64、0.25～64和0.25～2 μg/ml,F值分别为26.242、23.563、31.541和64.469,P均<0.05);RFP在MDR酶株的MIC值(2～64 μg/ml)显著高于非MDR的耐药菌株的MIC值(0.25 μg/ml,F=5.613,P<0.05).结论 本研究揭示了常用的12种抗结核药物的耐药程度与常规药敏检测结果 之间的关联规律,为临床医生根据常规药敏结果 制定更加有效的抗结核治疗方案提供重要的借鉴.     

Effect of serum isoniazid level on treatment outcomes among tuberculosis patients with slow response – A retrospective cohort study

BackgroundIn this study, we investigate the effects of low serum TB drug level on treatment outcome among TB patients with slow response in South Korea, where the prevalence of rapid acetylator is relatively high.MethodsAmong the pulmonary TB patients whose treatment outcomes were reported between 2014 and 2018 at Incheon St. Mary hospital, those who underwent TDM because of delayed culture conversion or reversion were included. Primary outcome was microbiological failure defined as (1) positive sputum culture after 120 days of treatment, or (2) culture-confirmed relapse within one year after treatment completion. Patients with culture conversion within 120 days and no relapse were classified as the final conversion group. Clinical characteristics and serum drug concentration at 2 h after administration (C_2hr) were compared between those two groups.ResultsA total of 55 pulmonary TB patients were included. Prevalence of subtherapeutic range of C_2hr for isoniazid and rifampin was 78.2% and 21.8%, respectively. With one year of follow-up, 21 cases were classified as the microbiological failure group, and 34 cases as the final conversion group. In a multivariable logistic regression model for predicting microbiological failure, C_2hr of isoniazid was the most significant predictor after adjusting for the effects of age and sex (adjusted odds ratio, 0.29; p = 0.009). In a tree-based classification model, C_2hr of isoniazid with cutoff level 2.5 μg/ml was the most important variable for predicting microbiological failure.ConclusionsLow serum isoniazid level was related to poor treatment outcomes among the TB patients with slow response.     

Tuberculous abscess of the brain stem

Three cases of tuberculous abscess of the brain stem were treated with excision of the abscess supplemented with antitubercular therapy for 12 to 18 months. The lesions were frankly purulent and tubercle bacilli were demonstrated in the pus. A computed tomography scan demonstrated the site and extent of the lesion. Two of three patients developed the abscess during the course of antitubercular therapy for associated tubercular lesions. In spite of modern antitubercular treatment the abscess did not resolve and surgical excision had to be employed as a curative treatment.     

Ankle tuberculosis: a report of four cases in a Japanese hospital

We report four patients suffering from ankle tuberculosis, which is an uncommon disease in Japan. All patients complained of swelling and pain in the affected ankle. Ankle tuberculosis is a disorder that can be easily misdiagnosed. The mean delay in diagnosis was 5.3 months in our series. All patients had already been diagnosed as having ankle tuberculosis by the time they visited our hospital in this series. The patients had been definitively diagnosed to have ankle tuberculosis by means of a needle biopsy in two cases, an open biopsy in one case, and on the basis of the clinical features in one case. All patients received antitubercular therapy and non-weight-bearing protective treatment. Antitubercular therapy was performed for an average of 14.3 months, and non-weight-bearing treatment was maintained for a mean of 4.5 months. The main treatments for such cases include open biopsy for an uncertain diagnosis, débridement for intractable synovitis, and arthrodesis for severely destroyed ankles with pain. All patients received some form of surgical intervention either from previous doctors or from us in this series. We conclude that most patients who suffer from ankle tuberculosis seem to need surgery in addition to adequate chemotherapy and non-weight-bearing protective treatment.An erratum to this article can be found at     

Antitubercular therapy induced liver function tests abnormalities in human immunodeficiency virus infected individuals

BackgroundBoth antitubercular therapy (ATT) and antiretroviral therapy (ART) can cause drug induced liver injury (DILI) in tuberculosis (TB) and human immunodeficiency virus (HIV) coinfection. The aim of this research was to study ATT-induced liver function test (LFT) abnormalities in HIV-infected patients.MethodsHIV-infected patients diagnosed with TB were evaluated with baseline LFT and CD4 counts. ATT regimen was modified if baseline LFT was significantly abnormal. Patients on protease inhibitors were given rifabutin instead of rifampicin. In patients on nevirapine-based ART, efavirenz was substituted for nevirapine. In ART-naive patients, the timing of introduction of ART was according to CD4 cell counts. LFT were repeated fortnightly or as clinically indicated for 10 weeks.ResultsWe studied 100 patients with HIV ([M – 67, F – 23], mean age: 40.05 ± 10.75 years, mean CD4 cell count: 239.157 ± 228.49 cells/dL). Sixty-one patients were on ART prior to diagnosis of TB. Baseline LFT abnormalities (n = 40) were similar in ART and non-ART group (28/61 vs 12/39, p = 0.13). After starting ATT, derangement of LFT was observed in majority of patients (99/100). However, liver sparing ATT was required only in 15 patients. Bilirubin >2.5 mg/dL was seen only in 9 patients. Significant rise in transaminases was commoner in patients on concurrent ART and ATT (p = 0.044) and with baseline LFT abnormalities (p = 0.00016). There was no case of acute liver failure or mortality.ConclusionMild LFT abnormalities are common in HIV-infected individuals on ATT. Concomitant use of ATT and ART and baseline LFT abnormalities increase the risk of significant DILI. However, with closer follow-up, serious liver injury can be prevented.     

抗结核药物性肝损伤的危险因素及发生机制

由于结核杆菌日益耐药、人口老龄化、激素的使用及艾滋病患者的增多,结核感染仍然是威胁人类健康的一大问题,异烟肼、利福平、呲嗪酰胺和乙胺丁醇作为一线用药,在抗结核的同时引起药物性肝损害(ATDILI)的情况不容忽视.本文就ATDILI的危险因素、常用药物的作用机制以及代谢酶基因多态性等作一综述.