A Prospective Study of Multidrug Resistance and a Pilot Study of the Safety of and Clinical and Microbiologic Response to Levofloxacin in Combination With Other Antimycobacterial Drugs for Treatment of Multidrug-Resistant Pulmonary Tuberculosis (MDRTB) in HIV-Infected Patients.

To determine the demographic, behavioral, clinical, and geographic risk factors associated with the occurrence of multidrug-resistant pulmonary tuberculosis (MDRTB). To evaluate the clinical and microbiological responses and overall survival of MDRTB patients who are treated with levofloxacin-containing multiple-drug regimens chosen from a hierarchical list. Per 9/28/94 amendment, to assess whether persistent or recurrent positive sputum cultures of patients who show failure or relapse are due to the same strain or reinfection with a new strain.
Among TB patients, there has been an increase in progressive disease due to the emergence of antimycobacterial drug-resistant strains of Mycobacterium tuberculosis. Failure to identify patients at high risk for MDRTB increases the hazard for both treatment failure and development of resistance to additional therapeutic agents. Efforts to improve survival in patients with MDRTB will depend on improved methods of assessing the risk of acquisition of MDRTB and identifying drug susceptibility patterns in a timely fashion.

开始日期-

申办/合作机构

National Institute of Allergy & Infectious Diseases

NCT02496572 / Unknown statusN/AIIT

Effectiveness of a Simplified Short Regimen for Multidrug Resistant Tuberculosis Treatment in Karakalpakstan, Uzbekistan

Multidrug resistant tuberculosis (MDR TB) is a growing problem and few people have access to adequate diagnosis and treatment. The current recommended treatment regimen for MDR TB has a minimum of 20 months duration with high toxicity. Scale up of MDR TB treatment is associated with high default rates, and experience in the Medecins Sans Frontieres (MSF) programme in Uzbekistan shows that the current standard treatment greatly limits the ability to scale up to meet the high rates of MDR TB in the region.
Evidence from Bangladesh in 2010 showed that a 9-month short-course regimen could achieve a relapse-free cure rate of 88%. Several countries in West Africa started implementing similar regimens with similar outcomes. Evidence of effectiveness of this shortened regimen among regions with high second line drug use and resistance is still limited.
The investigators propose an observational study under programmatic conditions to evaluate the effectiveness of a shortened course MDR TB regimen in the high MDR/extensively drug resistant (XDR) TB prevalence and high second-line drug resistance setting of Karakalpakstan, Uzbekistan.

开始日期2013-09-01

申办/合作机构

Medecins Sans Frontières (UK)

[+1]

NCT00042289 / CompletedN/AIIT

Pharmacokinetic Properties of Antiretroviral and Related Drugs During Pregnancy and Postpartum

IMPAACT P1026s is a Phase IV prospective clinical study to evaluate the pharmacokinetics (PKs) of antiretroviral (ARV) and tuberculosis (TB) medications in pregnant women and their infants. (Pharmacokinetics are the various interactions between a drug and the body.) This study also evaluated the PKs of certain ARVs in postpartum women before and after starting hormonal contraceptives. The PKs of these drugs were evaluated by measuring the amount of medicine present in blood and/or vaginal secretions.

开始日期2003-06-09

申办/合作机构

National Institute of Allergy & Infectious Diseases

[+1]

100 项与硫酸卷曲霉素相关的临床结果

登录后查看更多信息

100 项与硫酸卷曲霉素相关的转化医学

登录后查看更多信息

100 项与硫酸卷曲霉素相关的专利（医药）

登录后查看更多信息

731

项与硫酸卷曲霉素相关的文献（医药）

2024-10-16·Journal of Clinical Microbiology

Nanopore-based targeted sequencing test for direct tuberculosis identification, genotyping, and detection of drug resistance mutations: a side-by-side comparison of targeted next-generation sequencing technologies

Article

作者: Cirillo, Daniela Maria ; Di Marco, Federico ; Morgan, Godstime Stephen Kojo ; Batignani, Virginia ; Moghaddasi, Kiarash ; Cabibbe, Andrea Maurizio

ABSTRACTWe investigated the performance of the targeted next-generation sequencing (tNGS)-based Oxford Nanopore Diagnostics AmPORE TB assay, recently approved by the World Health Organization (WHO) as tuberculosis (TB) diagnostic test for the detection of drug resistance on respiratory specimens. A total of 104 DNA samples from Xpert MTB/RIF-positive TB sputum specimens were tested using the AmPORE TB kit, with the GenoScreen Deeplex Myc-TB as a comparative tNGS assay. For AmPORE TB, DNA samples were divided into five sequencing runs on the MinION device. Data analysis was performed using proprietary software. The WHO catalog of mutations was used for drug resistance interpretation. The assay achieved a high validity rate of 98% (102/104 DNA samples), homogeneous mean reads coverage across TB-positive specimens, and 100% positive and negative agreements for detecting mutations associated with resistance to rifampicin, pyrazinamide, fluoroquinolones, ethambutol, and capreomycin compared with Deeplex Myc-TB. The main discrepancies for the remaining drugs were attributable to the different assay panel designs. The AmPORE TB turnaround time was approximately 5–6 hours from extracted DNA to tNGS reporting for batches of 22 DNA samples. The AmPORE TB assay drastically reduced the time to tNGS reporting from days to hours and showed good performance for drug-resistant TB profiling compared with Deeplex Myc-TB.IMPORTANCE Targeted next-generation sequencing (tNGS) of Mycobacterium tuberculosis provides comprehensive resistance predictions matched to new multidrug-resistant/rifampicin-resistant tuberculosis regimens and received World Health Organization approval for clinical use in respiratory samples in 2024. The advanced version of the Oxford Nanopore Diagnostics AmPORE TB tNGS kit was evaluated in this study for the first time and demonstrated good performance, flexibility, and faster turnaround time compared with the existing solutions.

2024-10-01·The Lancet Infectious Diseases

Evaluating culture-free targeted next-generation sequencing for diagnosing drug-resistant tuberculosis: a multicentre clinical study of two end-to-end commercial workflows

Article

作者: Colman, Rebecca E ; Suresh, Anita ; De la Rossa, Andres ; Omar, Shaheed V ; Kambli, Priti ; Georghiou, Sophia B ; Hoogland, Christine ; Uplekar, Swapna ; Laurent, Sacha ; Maghradze, Nino ; Rodrigues, Camilla ; Rodwell, Timothy C ; Tukvadze, Nestani ; Seifert, Marva ; Joseph, Lavania

BACKGROUNDDrug-resistant tuberculosis remains a major obstacle in ending the global tuberculosis epidemic. Deployment of molecular tools for comprehensive drug resistance profiling is imperative for successful detection and characterisation of tuberculosis drug resistance. We aimed to assess the diagnostic accuracy of a new class of molecular diagnostics for drug-resistant tuberculosis.METHODSWe conducted a prospective, cross-sectional, multicentre clinical evaluation of the performance of two targeted next-generation sequencing (tNGS) assays for drug-resistant tuberculosis at reference laboratories in three countries (Georgia, India, and South Africa) to assess diagnostic accuracy and index test failure rates. Eligible participants were aged 18 years or older, with molecularly confirmed pulmonary tuberculosis, and at risk for rifampicin-resistant tuberculosis. Sensitivity and specificity for both tNGS index tests (GenoScreen Deeplex Myc-TB and Oxford Nanopore Technologies [ONT] Tuberculosis Drug Resistance Test) were calculated for rifampicin, isoniazid, fluoroquinolones (moxifloxacin, levofloxacin), second line-injectables (amikacin, kanamycin, capreomycin), pyrazinamide, bedaquiline, linezolid, clofazimine, ethambutol, and streptomycin against a composite reference standard of phenotypic drug susceptibility testing and whole-genome sequencing.FINDINGSBetween April 1, 2021, and June 30, 2022, 832 individuals were invited to participate in the study, of whom 720 were included in the final analysis (212, 376, and 132 participants in Georgia, India, and South Africa, respectively). Of 720 clinical sediment samples evaluated, 658 (91%) and 684 (95%) produced complete or partial results on the GenoScreen and ONT tNGS workflows, respectively, with 593 (96%) and 603 (98%) of 616 smear-positive samples producing tNGS sequence data. Both workflows had sensitivities and specificities of more than 95% for rifampicin and isoniazid, and high accuracy for fluoroquinolones (sensitivity approximately ≥94%) and second line-injectables (sensitivity 80%) compared with the composite reference standard. Importantly, these assays also detected mutations associated with resistance to critical new and repurposed drugs (bedaquiline, linezolid) not currently detectable by any other WHO-recommended rapid diagnostics on the market. We note that the current format of assays have low sensitivity (≤50%) for linezolid and more work on mutations associated with drug resistance is needed.INTERPRETATIONThis multicentre evaluation demonstrates that culture-free tNGS can provide accurate sequencing results for detection and characterisation of drug resistance from Mycobacterium tuberculosis clinical sediment samples for timely, comprehensive profiling of drug-resistant tuberculosis.FUNDINGUnitaid.

2024-10-01·The Lancet Infectious Diseases

Targeted next-generation sequencing to diagnose drug-resistant tuberculosis: a systematic review and meta-analysis

Review

作者: Günther, Gunar ; Göller, Pauline Carlotta ; Guebely De la Hoz, Freddy Fernando ; Minder, Beatrice ; Egger, Matthias ; Efthimiou, Orestis ; Omar, Shaheed Vally ; Lahousse, Adrien Philippe ; Fenner, Lukas ; Schwab, Tiana Carina ; Perrig, Lisa

BACKGROUNDTargeted next-generation sequencing (NGS) can rapidly and simultaneously detect mutations associated with resistance to tuberculosis drugs across multiple gene targets. The use of targeted NGS to diagnose drug-resistant tuberculosis, as described in publicly available data, has not been comprehensively reviewed. We aimed to identify targeted NGS assays that diagnose drug-resistant tuberculosis, determine how widely this technology has been used, and assess the diagnostic accuracy of these assays.METHODSIn this systematic review and meta-analysis, we searched MEDLINE, Embase, Cochrane Library, Web of Science Core Collection, Global Index Medicus, Google Scholar, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform for published and unpublished reports on targeted NGS for drug-resistant tuberculosis from Jan 1, 2005, to Oct 14, 2022, with updates to our search in Embase and Google Scholar until Feb 13, 2024. Studies eligible for the systematic review described targeted NGS approaches to predict drug resistance in Mycobacterium tuberculosis infections using primary samples, reference strain collections, or cultured isolates from individuals with presumed or confirmed tuberculosis. Our search had no limitations on study type or language, although only reports in English, German, and French were screened for eligibility. For the meta-analysis, we included test accuracy studies that used any reference standard, and we assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcomes for the meta-analysis were sensitivity and specificity of targeted NGS to diagnose drug-resistant tuberculosis compared to phenotypic and genotypic drug susceptibility testing. We used a Bayesian bivariate model to generate summary receiver operating characteristic plots and diagnostic accuracy measures, overall and stratified by drug and sample type. This study is registered with PROSPERO, CRD42022368707.FINDINGSWe identified and screened 2920 reports, of which 124 were eligible for our systematic review, including 37 review articles and 87 reports of studies collecting samples for targeted NGS. Sequencing was mainly done in the USA (14 [16%] of 87), western Europe (ten [11%]), India (ten [11%]), and China (nine [10%]). We included 24 test accuracy studies in the meta-analysis, in which 23 different tuberculosis drugs or drug groups were assessed, covering first-line drugs, injectable drugs, and fluoroquinolones and predominantly comparing targeted NGS with phenotypic drug susceptibility testing. The combined sensitivity of targeted NGS across all drugs was 94·1% (95% credible interval [CrI] 90·9-96·3) and specificity was 98·1% (97·0-98·9). Sensitivity for individual drugs ranged from 76·5% (52·5-92·3) for capreomycin to 99·1% (98·3-99·7) for rifampicin; specificity ranged from 93·1% (88·0-96·3) for ethambutol to 99·4% (98·3-99·8) for amikacin. Diagnostic accuracy was similar for primary clinical samples and culture isolates overall and for rifampicin, isoniazid, ethambutol, streptomycin, and fluoroquinolones, and similar after excluding studies at high risk of bias (overall sensitivity 95·2% [95% CrI 91·7-97·1] and specificity 98·6% [97·4-99·3]).INTERPRETATIONTargeted NGS is highly sensitive and specific for detecting drug resistance across panels of tuberculosis drugs and can be performed directly on clinical samples. There is a paucity of data on performance for some currently recommended drugs. The barriers preventing the use of targeted NGS to diagnose drug-resistant tuberculosis in high-burden countries need to be addressed.FUNDINGNational Institutes of Allergy and Infectious Diseases and Swiss National Science Foundation.

项与硫酸卷曲霉素相关的新闻（医药）

2023-07-27

·生物制品圈

盘点抗生素种类以及常用残留检测方法

抗生素，是指由微生物（包括细菌、真菌、放线菌属）或高等动植物在生活过程中所产生的具有抗病原体或其他活性的一类次级代谢产物，能干扰其他生活细胞发育功能的化学物质。抗生素等抗菌剂的抑菌或杀菌作用，主要是针对“细菌有而人（或其他动植物）没有”的机制进行杀伤，包含四大作用机理，即：抑制细菌细胞壁合成，增强细菌细胞膜通透性，干扰细菌蛋白质合成以及抑制细菌核酸复制转录。抗生素分类 01β-内酰胺类抗生素：青霉素类、头孢菌素类、β-内酰胺酶抑制药等02大环内酯类抗生素：红霉素、罗红霉素、阿奇霉素、克拉霉素等03氨基甙类抗生素：卡那霉素、链霉素、庆大霉素、依替米星等04四环素类抗生素：四环素、土霉素、强力霉素等 05林可霉素类抗生素：林可霉素和克林霉素 06氯霉素类抗生素：氯霉素和硫霉素 07喹诺酮类：氟哌酸、氧氟沙星、洛美沙星等“沙星” 08其他抗细菌的抗生素：去甲万古霉素、磷霉素、卷曲霉素、利福平等生物药中抗生素残留及检测方法目前抗生素的残留一般存在于疫苗类药物中，虽然抗生素不是疫苗中的必须成分，但在一些疫苗的制备过程中，为了防止细菌污染，需要添加一些抗生素。在最终成品前，还要尽量去除抗生素。我国在2010版以后的药典中均规定：疫苗中如果添加了抗生素，成品中所有抗生素累计残留量不得超过50ng/剂。抑菌圈测量法抑菌圈法又叫扩散法，是利用待测药物在琼脂平板中扩散使其周围的细菌生长受到抑制而形成透明圈，即抑菌圈。抑菌圈直径的大小是抗生素效价的直观体现，可以根据抑菌圈大小对抗生素的效价进行定性或定量的判定。抑菌圈法简单易行、成本低廉，是一种经典的检测方法，但此方法耗时较长，并且如果要降低人为判断结果的主观因素，需配备抑菌圈分析仪。液相色谱串联质谱法液相色谱串联质谱（LC-MS-MS）是继气质联用和液质联用以后发展起来的又一新型分离检测技术。其具有分离效率高、分析速度快、灵敏度高、易排除杂质干扰、定性定量精准等众多特点，非常适合于多组分快速检测。近年来，国内外众多学者也开始选用LC-MS-MS进行各种基质样品中抗生素的分析检测，灵敏度高，选择性和特异性较好，定性定量准确。但此方法需要配备相应质谱设备，操作复杂，且通量较低。酶联免疫吸附法酶联免疫吸附检测技术是一种基于抗原-抗体反应的测定方法，多用于测量蛋白质等大分子的检测，也适用于抗生素这种小分子物质。其原理是通过形成三明治结构（双抗夹心法）或竞争限量酶标抗体（竞争法）后，通过酶标记抗体与底物的显色反应，根据颜色的深浅（吸光度）进行定量检测。相较于前两种抗生素检测方法，该方法用时短，操作简便，定量准确且具有高通量等特点，非常适合抗生素的检测。君研生物抗生素类定量检测试剂盒君研生物自主研发的“抗生素类残留定量检测试剂盒”采用间接竞争ELISA法，可以快速，有效地检测样品中抗生素的残留量。卡那霉素定量检测试剂盒卡那霉素是氨基糖甙类抗生素，应用于动物疾病的治疗、菌株筛选以及细胞和基因治疗药物原料制备中，由于其具有神经毒性和肾脏毒性，损害第8对脑神经，导致前庭和耳蜗损伤。在动物食品、生物药品中的残留会影响人类健康，甚至引起过敏反应。欧美国家及我国均要求其限量使用。君研生物的卡那霉素定量检测试剂盒采用间接竞争ELISA方法，微孔条上预包被的偶联卡那霉素抗原与样品中残留的卡那霉素竞争结合酶标记的抗卡那霉素单克隆抗体，之后通过加入TMB底物显色，使用酶标仪检测吸光值，吸光值与样品中卡那霉素的含量成负相关。本试剂盒操作时间仅需一小时左右，试剂盒灵敏度为0.05ng/ml，线性范围为0.05ng/ml-5ng/ml。产品优势 | PRODECT ADVANTAGE性能指标 | PERFORMANCE INDEX验证数据 | VALIDATION DATA 庆大霉素定量检测试剂盒庆大霉素系从放线菌科单孢子属发酵培养液中提得，系碱性化合物，是常用的氨基糖苷类抗生素，广泛应用于培养基配制。在临床上主要用于治疗细菌感染。庆大霉素具有神经毒性、肾脏毒性以及耳毒性。其在动物食品、生物药品中的残留会影响人类健康，甚至引起过敏反应。欧美国家及我国均要求其限量使用。君研生物的庆大霉素定量检测试剂盒采用间接竞争ELISA方法，微孔条上预包被的庆大霉素抗原与样品中残留的庆大霉素竞争结合酶标庆大霉素单克隆抗体，之后加入酶标二抗，再通过加入TMB底物显色，使用酶标仪检测吸光值，吸光值与样品中庆大霉素的含量成负相关。本试剂盒操作时间仅需一小时左右，试剂盒灵敏度为0.1ng/mL，线性范围为0.1ng/mL-10ng/mL。产品优势 | PRODECT ADVANTAGE性能指标 | PERFORMANCE INDEX验证数据 | VALIDATION DATAEND君研产品推荐关于君研君研生物科技（山西）有限公司作为独立创新的研发、生产和销售一体型企业，专注于为生物医药产业提供符合国际标准的质量安全检测产品和服务。公司由海归科学家与业内资深专家领队，通过了产品设计开发、生产和服务全过程 ISO13485 体系认证，建设约3200 平米符合 cGMP 标准和 ISO 13485:2016 体系要求的研发生产基地，为国内抗体、疫苗、细胞基因治疗、核酸药物等领域生物药企以及CRO/CDMO、科研机构和监管机构提供了国际品质的产品和专业的技术服务。公司结合生物医药行业发展需求，已经覆盖包含工艺杂质残留、宿主细胞核酸及蛋白残留、含量测定、外源污染物、载体基因安全性分析等检测项目在内的 30 余种标准化检测产品，拥有专利类知识产权 10 余项。君研生物坚持生物原料中国造，以“专业技术服务人类健康”为理念，以打造中国品牌为己任，坚持持续创新的态度，为客户创造价值，为人类健康贡献力量。国医械华光认证证书联系方式CONTACT INFORMATIONCONTACTNFORMATIN销售电话15234188795技术支持18734150104/19503412257联系邮箱junyans21@163.com公司官网www.junyanbios.cn

疫苗

100 项与硫酸卷曲霉素相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D00135	硫酸卷曲霉素	J04AB30	DB00314

研发状态

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
肺结核	中国	辽宁倍奇药业有限公司	1996-01-01
肺结核	中国	河南泰丰生物科技有限公司	1996-01-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASN2018	N/A	慢性肾病	-	Capreomycin	鑰鏇衊觸膚夢獵窪遞廠(蓋鏇繭顧製膚壓壓願夢) = This case demonstrates a rapid, severe alteration of the GFR in a diabetic, normotensive patient with no evident proteinuria. The biopsy did not reveal kidney impairment from the DM. The literature reports few cases on nephrotoxicity from CPM. This study emphasizes the importance of strict controlling the GFR in patients on CPM, especially the elderly and those with comorbidities. 憲壓醖製鹽壓齋窪選醖 (餘鹹遞襯觸鹹遞構顧壓 )	-	2018-10-23
				Rifampicin, Isoniazid, Pyrazinamide, Etambutol, Levofloxacin, Terizidone