A Multi-centre, Randomised Trial Comparing a Novel Combination Treatment (Arm D - Intravenous Sulbactam-durlobactam in Combination With Intravenous Ceftriaxone, Oral Amoxicillin, Oral Azithromycin and Oral Clofazimine) Versus Standard of Care Treatments for the Intensive Phase of Treatment for Mycobacterium Abscessus Pulmonary Disease in People With or Without Cystic Fibrosis in the Finding the Optimal Regimen for Mycobacterium Abscessus Treatment (FORMaT) Adaptive Platform Trial

The goal of this clinical trial is to learn if a new combination antibiotic treatment (Arm D) works to treat a rare lung condition called mycobacterium abscessus pulmonary disease in people of any age and sex, when compared to the standard treatments. It will also learn about the safety of this new combination antibiotic treatment when compared to the standard treatments. The main questions it aims to answer are:
* How well does Arm D treat mycobacterium abscessus pulmonary disease?
* What side effects does Arm D cause when used to treat mycobacterium abscessus pulmonary disease? Researchers will compare Arm D to the current standard of care treatments to see if Arm D treats mycobacterium abscessus pulmonary disease better and if it will cause less side effects.
Participants will:
* Be screened and recruited to the FORMaT adaptive platform trial (NCT04310930)
* Be given Arm D for 4 weeks or standard of care treatments for 6 weeks.
* Be reviewed by the study doctors weekly for checkups and tests.
* Provide respiratory samples (sample coughed up from the chest), respond to quality-of-life questionnaires, have CT lung scans and blood tests.

开始日期2027-04-01

申办/合作机构

The University of Queensland

[+1]

NCT07486024

/ Not yet recruiting临床3期IIT

Feasibility of the Application of a New Six-month Treatment for Multidrug-resistant Tuberculosis (MDR-TB) Patients in France - FAST-MDR

The FAST-MDR trial is an externally-controlled, multicentre trial with one prospective arm, evaluating the non-inferiority of the effectiveness of BPaLM in the interventional arm versus the effectiveness of the long, conventional regimen in a French historical cohort of MDR-TB patients (2006-2022). In light of recent WHO recommendations suggesting using BPaLM as a first choice for routine MDR-TB treatment and of the expected benefits of BPaLM over the standard treatment, there will be no internal comparator arm in the study.

开始日期2026-04-01

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

[+1]

NCT07069582

/ Not yet recruiting临床1期IIT

Plasma and Breastmilk Exposures to Antituberculosis Drugs in Breastfeeding Women: an Open-label, Randomized, Six-arm, Single-dose, Pharmacokinetic Study

This study is a sub-study of the SSTARLET trial (NCT06498414). The overall aim is to assess the pharmacokinetic profiles after taking a single dose of rifampicin, isoniazid, levofloxacin, rifapentine, and bedaquiline in breastfeeding women and the excretion of these drugs in breast milk, with the hope of including breastfeeding women in future clinical trials of TPT, including expanding the inclusion criteria of the SSTARLET trial. In this study, healthy breastfeeding women who fulfill the eligibility criteria will be enrolled from several primary health care centers in Bandung, which will be referred to the TB Research Clinic of the Universitas Padjadjaran, Bandung, Indonesia. Ten participants will be randomized to each of the following six study arms:
* Arm A: Single-dose rifampicin at 10 mg/kg body weight (RIF10).
* Arm B: Single-dose rifampicin at 20 mg/kg body weight (RIF20).
* Arm C: Single-dose isoniazid at 5 mg/kg body weight (INH5).
* Arm D: Single-dose levofloxacin at 10-15 mg/kg body weight (LFX10-15).
* Arm E: Single-dose rifapentine at 10 mg/kg body weight (RPT10).
* Arm F: Single-dose bedaquiline at 400 mg (BDQ400).

开始日期2026-04-01

申办/合作机构

Universitas Padjadjaran

100 项与富马酸贝达喹啉相关的临床结果

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2,280

项与富马酸贝达喹啉相关的文献（医药）

2026-04-01·INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES

Treatment outcomes and drug-related adverse events across four short-course RR-TB regimens in South Africa: A retrospective analysis

Article

作者: Menzies, Dick ; Oelofse, Suzette ; Dheda, Keertan ; Perumal, Rubeshan ; Schaaf, Hendrik Simon ; Campbell, Jonathon R ; Conradie, Francesca ; Naidoo, Kogieleum ; Amusa, Lateef Babatunde ; Romanowski, Kamila ; Ndjeka, Norbert ; Meintjes, Graeme ; Romero, Rodolfo ; Mathema, Hlengani

BACKGROUND:

Shorter all-oral regimens for the treatment of multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) have improved efficacy, but their performance under programmatic conditions remains insufficiently characterized.

METHODS:

We retrospectively evaluated treatment outcomes and drug-related adverse events (AEs) among 396 randomly selected patients from four facilities in three provinces across South Africa. Patients received four different short-course regimens sequentially introduced into national programme: i) injectable 9-11-month (injectable-regimen), ii) bedaquiline-ethionamide-containing (ethionamide-regimen), iii) bedaquiline-linezolid-containing (linezolid-regimen), and iv) bedaquiline-pretomanid-linezolid-levofloxacin regimen (BPaL-L).

RESULTS:

Compared with the injectable regimen, the ethionamide-regimen (adjusted odds ratio [aOR] 1.98, 95% CI: 1.07-3.65) and BPaL-L (aOR 2.31; 95% CI: 1.23-4.33) had higher odds of treatment success; the linezolid-regimen did not (aOR 1.68; 95% CI: 0.92-3.06). The linezolid and BPaL-L regimens had similar odds of grade 3 or higher AEs, and comparable AE-related drug discontinuation. Toxicity patterns differed, from hearing loss with injectables to anaemia and neurotoxicity with BPaL-L.

CONCLUSION:

Under programmatic conditions, the BPaL-L regimen achieved the highest treatment success while maintaining manageable safety profiles. These findings provide valuable evidence to guide patient management and support implementation of novel MDR/RR-TB regimens in high-burden settings.

2026-04-01·DRUG DEVELOPMENT RESEARCH

Halting Tuberculosis in Its Tracks: Advances and Strategies for Discovering Therapeutic Targets in Mycobacterium tuberculosis

Review

作者: Singh, Gyanendra ; Shrivastava, Rahul ; Sharma, Ayushi

ABSTRACT:

Tuberculosis is a global emergency. Despite two decades of intense research to understand and cure the disease, biological uncertainties prevail and hamper the therapeutic progress. Increasing incidences of multidrug‐resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis strains further complicate tuberculosis control. Modern research, therefore, focuses on development of new antitubercular drugs to treat drug‐resistant tuberculosis and shorten the duration of the standard chemotherapy. Fortunately, the recent accelerated approval of delamanid and bedaquiline for use in MDR and XDR tuberculosis has reinvigorated antitubercular research. Although progresses in tuberculosis drug discovery are being made following the availability of M. tuberculosis genome and progressions in molecular biology, novel drug targets and leads are continuously required to strengthen the tuberculosis therapeutic pipeline. Discovery of new targets has eventually promoted tuberculosis therapy, and will keep paving the foundation for generating the future wave of tuberculosis drug leads. This review summarizes important M. tuberculosis drug targets such as F 1 /F 0 ATP synthase, isocitrate lyase, β ‐ketoacyl‐ACP synthases KasA and KasB, QcrB, and mycobactin biosynthesis enzymes MbtA and MbtI, and drugs under preclinical and clinical development stages that aim at making drug discovery breakthroughs. It also discusses the strategies that entail discovery of new mycobacterial therapeutic determinants and provide ideas for development of more efficient drugs. The article comprehensively provides a better understanding of M. tuberculosis drug targets, along with opening new ventures for tuberculosis control and treatment.

2026-03-01·CLINICAL MICROBIOLOGY AND INFECTION

A 6- to 9-months oral regimen for rifampicin-resistant tuberculosis: a randomized open-label noninferiority trial in China

Article

作者: Qian, Yuan ; Xing, Yajiao ; Xiao, Mingying ; Zhang, Yena ; He, Zebao ; Li, Jinlan ; Wang, Jing ; Feng, Shun ; Chen, Yu ; Wu, Qianhong ; Li, Yiming ; Zhang, Wenhong ; Shi, Jichan ; Yu, Hongying ; Lan, Yuanbo ; Yi, Hengzhong ; Zhang, Yungui ; Liu, Haiqing ; Li, Yang ; Luo, Jianfeng ; Chen, Yuanyuan ; Zhou, Yong ; Zhao, Yanlin ; Chen, Bin ; Sun, Feng ; Wei, Xiaolin ; Huang, Ya ; Cai, Cui ; Zhang, Yilin ; Xu, Lin

OBJECTIVES:

Despite advancements in shorter, oral regimens for drug-resistant tuberculosis, more options are needed to extent patient benefits. We conducted a trial to evaluate the noninferiority of an all-oral regimen compared with the injectable-containing regimen.

METHODS:

In an open-label, randomized noninferiority trial in China, participants with rifampicin-resistant pulmonary tuberculosis were assigned 1:1 to a 6- to 9-month all-oral regimen (levofloxacin, linezolid, cycloserine, clofazimine and/or pyrazinamide) and a 9-month injectable-containing control regimen. The primary outcome was a favourable outcome at 84 weeks after treatment initiation, defined by two consecutive, negative cultures with no previous unfavourable outcome, using a noninferiority margin of 10%.

RESULTS:

Between 2 June 2020, and 1 December 2021, 660 participants were enrolled and 354 underwent randomization. A total of 312 and 260 participants were included in the modified intention-to-treat and the per-protocol analysis, respectively. In the modified intention-to-treat analysis, 76.1% of participants in the oral group and 63.7% of those in the control group had a favourable outcome at 84 weeks (difference, 12.4%; 95% CI, 2.4-22.5%; noninferiority p < 0.0001). In the per-protocol analysis, 84.4% of participants in the oral group and 73.5% of participants in the control group had a favourable outcome (difference, 10.9%; 95% CI, 1.1-20.7%; noninferiority p < 0.0001). Grade 3 to 5 adverse events occurred in 69.1% of participants in the control group and 59.5% in the oral group. The most common grade 3 to 5 adverse events were QTcF (corrected QT interval calculated with Fridericia's formula) prolongation, affecting 44.6% of participants in the control group and 29.5% of participants in the oral group. Hepatobiliary disorder occurred more frequently in the control group (21.7%) compared with the oral group (7.5%).

CONCLUSIONS:

The all-oral regimen was noninferior to the 9-month injectable-containing regimen, offering an alternative for patients lacking access to bedaquiline, delamanid or pretomanid. However, its efficacy against the latest WHO-recommended bedaquiline-containing regimens requires further validation.

189

项与富马酸贝达喹啉相关的新闻（医药）

2026-03-20

·EINPresswire

ABL Diagnostics Expands HIV Sequencing Expertise into TB Drug Resistance Profiling with New NGS Solutions

WOIPPY, FRANCE, March 20, 2026 / EINPresswire.com / -- ABL Diagnostics (FR001400AHX6 – “ABLD”), an innovative company specialized in microbiology and pathogen sequencing, today announced major advancements in its Mycobacterium tuberculosis (MTB) portfolio, combining its current CE-IVD marked DeepChek ® Assay 13‑Plex KB and BacterioChek software with the development of new research next‑generation sequencing (NGS) solutions for comprehensive drug resistance detection and genomic surveillance. At the core of its current offering, ABL Diagnostics commercializes the CE-IVD marked DeepChek ® Assay 13-Plex KB Drug Susceptibility Testing assay, a multiplex PCR solution enabling the detection of key resistance-associated mutations across first- and second-line anti-TB drugs. Designed for use with NGS workflows, the assay supports amplification of MTB DNA directly from clinical specimens and provides actionable genotyping data to guide treatment decisions. This solution is complemented by BacterioChek, ABL Diagnostics’ CE-IVD software for automated analysis and interpretation of MTB Next-Generation Sequencing data, delivering standardized and clinically relevant reports to support laboratories and clinicians. Building on this integrated workflow, ABL Diagnostics has developed two new solutions intended for research use for now: - A 19-gene resistance panel, expanding coverage beyond the current DeepChek ® Assay 13-Plex but with the same input DNA extraction and using the same PCR cycling program, ensuring seamless adoption for existing users. This panel already covers the full set of genes known to be associated with resistance to currently prescribed anti-tuberculosis drugs. These include first and second line treatments such as rifampicin (rpoB), isoniazid (katG, inhA), ethambutol (embB), pyrazinamide (pncA), fluoroquinolones (gyrA, gyrB), aminoglycosides such as amikacin and kanamycin (rrs, eis), as well as newer and repurposed drugs like linezolid (rplC, rrl) and bedaquiline (atpE, Rv0678). By integrating an expanded set of resistance‑associated genes, the 19‑gene panel delivers broader and more informative insights into MTB drug resistance profiles, supporting ongoing research on emerging therapeutic targets and contributing to the development of next‑generation strategies for improved disease management. - A whole genome MTB solution (~4.4 Mb) based on capture technology, enabling broad exploration of resistance associated mutationsand supporting high-resolution epidemiological and transmission studies. Beyond addressing current research needs, this whole genome approach offers a forward looking platform capable of uncovering resistance mechanisms related to both established and emerging therapeutic options. This includes next-generation agents such as bedaquiline, delamanid, pretomanid, and linezolid, as well as future compounds under development. By capturing the full genomic landscape of MTB, this solution provides an adaptable foundation for ongoing research Both solutions will be commercialized for research use only from Q2 2026. ABL Diagnostics is actively seeking partner laboratories for verification and validation studies. The regulatory roadmap will then progressively evaluate potential future CE IVD marking under the new EU IVD regulation and WHO review process. Tuberculosis remains one of the leading infectious diseases worldwide, with significant unmet medical needs driven by the growing burden of drug-resistant forms. These trends are consistent with data from the U.S. CDC TB Surveillance Report , which highlights evolving resistance patterns in recent isolates. According to recent global estimates, hundreds of thousands of new multidrug-resistant (MDR) and rifampicin-resistant TB cases are reported annually, with treatment success rates remaining substantially lower than for drug-susceptible TB. In addition, surveillance data highlights the continued emergence of resistance to key drug classes, including fluoroquinolones and second-line injectable agents, further complicating treatment strategies. ( https://www.cdc.gov/tb-surveillance-report-2024/data/drug-resistance.html ) The global market for drug-resistant tuberculosis diagnosis and treatment is expanding rapidly, driven by increasing incidence, the complexity and cost of treatment regimens, and strong support from public health organizations and funding bodies. Market growth projections are supported by recent industry analyses (HTF Market Insights, “Drug Resistant Tuberculosis Treatment Market”). Market analysts project sustained growth over the coming years, fueled by the adoption of advanced molecular diagnostics and sequencing technologies that enable faster, more accurate, and scalable resistance profiling. The adoption of NGS in clinical microbiology is accelerating this shift toward comprehensive resistance profiling and genomic surveillance, enabling healthcare systems to improve patient outcomes while strengthening public health responses to TB transmission. ( https://www.htfmarketinsights.com/report/4354561-drugresistant-tuberculosis-treatment-market ) “Our CE-IVD DeepChek ® Assay 13-Plex and BacterioChek software already provide laboratories with a robust and integrated solution for MTB drug resistance testing,” said Dr. Sofiane Mohamed, Head of R&D at ABL Diagnostics. “With our expanded research pipeline, including a 19-gene panel and a whole genome approach, we are extending this foundation to deliver more research tools for ongoing research, helping accelerate the discovery of new resistance pathways and informing next generation strategies for improved disease management and therapeutic innovation.” About ABL Diagnostics (ABLD) ABL Diagnostics (ABLD) is an international company that specializes in innovative molecular biology tests and global solutions for its customers: - Molecular polymerase chain reaction (PCR) detection – UltraGene, and - Genotyping by DNA sequencing – DeepChek ® . ABL Diagnostics markets its entire product range globally through its own sales team and a network of exclusive distributors active on all continents. ABL Diagnostics' customers are academic clinical pathology laboratories, private reference laboratories and researchers willing to implement innovative and robust microbiological content in constant expansion. ABL Diagnostics has been marketing the products and services of its sister company CDL Pharma since the second half of 2025 through an intra-group strategy agreement. An expanding portfolio of microbiology products: - HIV – Drug resistance testing, including a whole genome kit. - SARS-CoV-2, Tuberculosis, Hepatitis B and C – Advanced Detection Solutions. - Microbiome and taxonomy – 16s/18s RNA-based analyses. - Other viral and bacterial targets – Comprehensive molecular assays. Integrated Solutions - Real-time syndromic PCR tests - Nadis ® – Patient Medical Record used in more than 200 hospitals in France for the management of HIV and hepatitis. - MediaChek ® – Clinical Sample Collection Kits. ABL Diagnostics, headquartered in Woippy, is a public limited company listed on compartment B of the regulated market of Euronext in Paris (Euronext: ABLD – ISIN: FR001400AHX6). These molecular biology products generate recurring revenues and cover one of the largest portfolios of applications in microbiology. Dr Sayada ABL Diagnostics SA +33 7 83 64 68 50 email us here Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

临床研究诊断试剂

2026-03-15

·道道之道

【本周医刊】2026年第11周医学期刊更新

2026年第11周（2026.03.08-2026.03.14）重要医学期刊论著更新如下： 1.综合期刊 LANCET 题目：Hormone therapy use and duration with postoperative radiotherapy for recurrent prostate cancer: an individual patient data meta-analysis 翻译：复发性前列腺癌术后放疗联合内分泌治疗的使用与时长：一项个体患者数据荟萃分析题目：Pimicotinib versus placebo for tenosynovial giant cell tumour (MANEUVER): an international, randomised, placebo-controlled, phase 3 trial 翻译：吡西替尼对比安慰剂治疗腱鞘巨细胞瘤（MANEUVER）：一项国际、随机、安慰剂对照Ⅲ期临床试验题目：Integrated community-based versus facility-based care for people with HIV, diabetes, and hypertension in sub-Saharan Africa (INTE-COMM): an open-label, multicountry, cluster-randomised trial 翻译：撒哈拉以南非洲地区基于社区整合照护vs 机构照护用于HIV、糖尿病及高血压患者（INTE‑COMM）：一项开放标签、多国、整群随机试验 NEW ENGLAND JOURNAL OF MEDICINE 题目：Bleeding Risk with Apixaban vs. Rivaroxaban in Acute Venous Thromboembolism 翻译：阿哌沙班与利伐沙班在急性静脉血栓栓塞中的出血风险比较题目：Romiplostim versus Placebo for Chemotherapy-Induced Thrombocytopenia 翻译：罗米司亭对比安慰剂治疗化疗所致血小板减少症题目：DB-OTO Gene Therapy for Inherited Deafness 翻译：DB-OTO 基因治疗用于遗传性耳聋题目：Fixed-Duration versus Continuous Treatment for Chronic Lymphocytic Leukemia 翻译：固定疗程治疗对比持续治疗用于慢性淋巴细胞白血病 JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 题目：Acetaminophen (Paracetamol) or Opioid Analgesia Added to Ibuprofen for Children’s Musculoskeletal Injury: Two Randomized Clinical Trials 翻译：布洛芬联合对乙酰氨基酚（扑热息痛）或阿片类镇痛药用于儿童肌肉骨骼损伤：两项随机临床试验题目：Effect of Automated Closed-Loop Ventilation vs Protocolized Conventional Ventilation on Ventilator-Free Days in Critically Ill Adults: A Randomized Clinical Trial 翻译：自动化闭环通气与方案化常规通气对重症成年患者无呼吸机天数的影响：一项随机临床试验题目：Donation After Circulatory Death Heart Transplant Without Preimplant Reanimation Using Rapid Ultraoxygenated Recovery 翻译：采用快速超氧合复苏、无需移植前复苏的循环死亡后捐献心脏移植 NATURE MEDICINE 题目：A structure-based mRNA vaccine for Nipah virus in healthy adults: a phase 1 trial 翻译：基于结构设计的尼帕病毒 mRNA 疫苗在健康成人中的Ⅰ期临床试验题目：A cognitive layer architecture to support large-language model performance in psychotherapy interactions 翻译：一种用于提升大语言模型在心理治疗互动中表现的认知层架构题目：Blood phosphorylated tau elevation as a biomarker in immunoglobulin light chain and transthyretin amyloidosis 翻译：血磷酸化 tau 蛋白升高可作为免疫球蛋白轻链淀粉样变性与转甲状腺素蛋白淀粉样变性的生物标志物题目：Antibiotic use and gut microbiome composition links from individual-level prescription data of 14,979 individuals 翻译：基于 14979 例个体处方数据揭示抗生素使用与肠道微生物组组成的关联题目：Effects of daily multivitamin–multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial 翻译：COSMOS 随机临床试验：每日复合维生素–矿物质及可可提取物补充对表观遗传衰老时钟的影响题目：Physical activity for public health in the 21st century 翻译：21 世纪面向公共卫生的体力活动 BMJ-BRITISH MEDICAL JOURNAL 题目：Chemotherapy for gastric or gastro-oesophageal junction adenocarcinoma 翻译：胃或胃食管结合部腺癌的化疗题目：Prenatal antiseizure drug exposure and risk of neurodevelopmental disorders in children 翻译：产前抗癫痫药物暴露与儿童神经发育障碍风险 INNOVATION（本周无更新） LANCET DIGITAL HEALTH（本周无更新） NPJ DIGITAL MEDICINE 题目：A multicenter multifunctional assessment of large language models in pure-tone audiogram interpretation for patients 翻译：大语言模型在患者纯音测听图判读中的多中心多功能评估题目：AI literacy mediates AI assisted diagnosis participation and critical thinking among medical students under supervision 翻译：监督下医学生的 AI 素养在AI 辅助诊断参与度与批判性思维间的中介作用题目：The role of agentic artificial intelligence in healthcare: a scoping review 翻译：自主智能体在医疗保健中的作用：一项范围综述题目：Time and person sensitive foundation model for disease prediction and risk stratification 翻译：面向疾病预测与风险分层的时间—人群敏感基础模型题目：Artificial Intelligence-powered tiered early warning framework addressing high false alarm rates for in-hospital mortality prediction 翻译：针对院内死亡预测高误报率的 AI 驱动分级预警框架题目：Federated clinical concept and disease semantic learning for congenital heart disease diagnosis 翻译：面向先天性心脏病诊断的联邦临床概念与疾病语义学习题目：Designing digital mental health interventions for older adults: a scoping review 翻译：面向老年人的数字心理健康干预设计：一项范围综述题目：Meta-analysis of computerised working memory training: behavioural gains, training parameters, transfer mechanisms, and neural correlates 翻译：计算机化工作记忆训练的 Meta 分析：行为获益、训练参数、迁移机制及神经关联题目：Continuous assessment of daily-living gait using self-supervised learning of wrist-worn accelerometer data 翻译：基于腕部加速度计自监督学习的日常生活步态连续评估题目：Identifying what works in mental health apps through meta-regression analyses of 169 trials 翻译：通过 169 项试验的Meta 回归分析识别心理健康APP 中的有效成分题目：Using clinical simulation to evaluate a video telehealth consultation summary application 翻译：利用临床模拟评估视频远程医疗会诊总结应用程序题目：Automated interpretation of fetal cardiac function evaluation from the echocardiogram 翻译：胎儿超声心动图心功能评估的自动化判读题目：Immersive competence as a source of bias in virtual reality clinical assessment 翻译：沉浸胜任力作为虚拟现实临床评估中的偏倚来源题目：Personalised health plan development using agentic AI in Singapore’s national preventive care programme: a pilot study 翻译：新加坡国家预防保健计划中利用自主 AI 制定个性化健康方案：一项预试验题目：Performance of breast cancer risk prediction algorithms across mammography systems in the UK screening programme 翻译：英国筛查项目中不同乳腺 X 线系统间乳腺癌风险预测算法的性能 2.肿瘤学 CA-A CANCER JOURNAL FOR CLINICIANS 题目：Aumolertinib with carboplatin–pemetrexed versus aumolertinib for nonsmall cell lung cancer with EGFRand concomitant tumor suppressor genes (ACROSS2): An open-label, multicenter, randomized phase 3 study 翻译：阿美替尼联合卡铂–培美曲塞对比阿美替尼单药治疗伴EGFR 突变及共存抑癌基因改变的非小细胞肺癌（ACROSS2）：一项开放标签、多中心、随机Ⅲ期研究题目：Targeting tumor suppressor gene co-mutations in EGFR-mutant nonsmall cell lung cancer: How ACROSS2 sharpens the case for early intensification 翻译：靶向 EGFR 突变非小细胞肺癌中的抑癌基因共突变：ACROSS2研究如何为早期强化治疗提供关键证据 ANNALS OF ONCOLOGY 题目：OPTIMAL: A Multinational Phase III Study of Oral Paclitaxel (DHP107) versus Intravenous Weekly Paclitaxel in HER2-Negative Recurrent or Metastatic Breast Cancer 翻译：OPTIMAL 研究：口服紫杉醇（DHP107）对比静脉每周紫杉醇治疗HER2 阴性复发或转移性乳腺癌的一项国际多中心Ⅲ期研究题目：MTAP Loss Is Frequent in Oncogene-Driven NSCLC and May Confer Sensitivity to Combined PRMT5 Inhibitors and Targeted Therapies 翻译：MTAP 缺失在癌基因驱动型非小细胞肺癌中较为常见，或可增加对PRMT5 抑制剂联合靶向治疗的敏感性 JOURNAL OF CLINICAL ONCOLOGY（本周无更新） LANCET ONCOLOGY（本周无更新） JOURNAL OF THORACIC ONCOLOGY（本周无更新） JAMA ONCOLOGY（本周无更新） CANCER RESEARCH（本周无更新） CLINICAL CANCER RESEARCH（本周无更新） JOURNAL OF THE NATIONAL CANCER CENTER（本周无更新） JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE 题目：Targeting CDK12 disrupts estrogen-receptor chromatin recruitment and ER-MED1 transcription in advanced ER+ breast cancer 翻译：靶向 CDK12 可破坏晚期ER + 乳腺癌中雌激素受体的染色质募集及ER-MED1 转录题目：Early-detection and prevention effects of screening sigmoidoscopy: evidence from randomized trials revisited 翻译：筛查性乙状结肠镜的早诊与预防作用：重新审视随机试验证据题目：What matters to society when making decisions about reimbursing drugs for prostate cancer: a discrete choice experiment 翻译：前列腺癌药物报销决策中社会关注因素：一项离散选择实验题目：Different diabetes types and pancreatic ductal adenocarcinoma: a Mendelian randomization and pathway/gene-set analysis 翻译：不同糖尿病类型与胰腺导管腺癌：孟德尔随机化与通路/ 基因集分析题目：Optimizing oncology drug development: systematic review of 22 years of myeloma randomized controlled trials 翻译：优化抗肿瘤药物研发：22 年间骨髓瘤随机对照试验的系统评价题目：Unmet social needs and colorectal cancer testing at 45-49 since the 2021 USPSTF recommendation 翻译：2021 年USPSTF 建议后45–49岁人群未满足的社会需求与结直肠癌筛查题目：Liver fat and clinical outcomes in individuals with stage I-III colon or rectal cancer 翻译：Ⅰ–Ⅲ期结直肠癌患者的肝脏脂肪与临床结局题目：Tattoos and risk of cutaneous melanoma and nonmelanoma skin cancer in France 翻译：法国人群纹身与皮肤黑色素瘤及非黑色素瘤皮肤癌风险题目：Association of human papillomavirus on risk of HIV acquisition in African women: analyses from MTN-020/ASPIRE 翻译：人乳头瘤病毒与非洲女性 HIV 感染风险的关联：MTN-020/ASPIRE研究分析题目：Income after cancer across gender and age among Canadian adolescents and young adults 翻译：加拿大青少年及青年癌症患者术后收入的性别与年龄差异题目：Health-related quality of life with first- vs second-line CDK4/6 inhibitor use in advanced breast cancer: results from the SONIA trial 翻译：晚期乳腺癌一线与二线 CDK4/6 抑制剂治疗的健康相关生活质量：SONIA试验结果题目：Neighborhood deprivation on increasing deficit accumulation in older breast cancer survivors and noncancer control individuals 翻译：社区贫困对老年乳腺癌幸存者与非癌症对照者缺陷累积加重的影响题目：Potential role of perceived discrimination and sociodemographics on racial disparities in breast cancer symptom burden 翻译：感知歧视与社会人口学特征对乳腺癌症状负担种族差异的潜在作用题目：The impact of HIV on cervical cancer elimination in KwaZulu-Natal: a comparative modeling analysis 翻译：南非夸祖鲁 - 纳塔尔省HIV 对宫颈癌消除的影响：一项比较模型分析 3.内分泌学与代谢 LANCET DIABETES & ENDOCRINOLOGY（本周无更新） DIABETES CARE（本周无更新） 4.心血管病学 CIRCULATION 题目：Clinical Spectrum of Children With Parvovirus B19–Associated Acute Myocarditis 翻译：细小病毒 B19 相关急性心肌炎患儿的临床表型谱题目：Prospective Associations of Obesity and Obesity Severity With 9 Cardiovascular Outcomes: The Cross-Cohort Collaboration 翻译：肥胖及肥胖严重程度与 9 种心血管结局的前瞻性关联：跨队列协作研究题目：GRSF1 Protects Against Heart Failure by Maintaining BCAA Homeostasis 翻译：GRSF1 通过维持支链氨基酸稳态抵御心力衰竭题目：CXCR6+ T Cells Drive Immune Checkpoint Inhibitor Myocarditis 翻译：CXCR6⁺ T 细胞驱动免疫检查点抑制剂相关性心肌炎 EUROPEAN HEART JOURNAL 题目：Transcatheter edge-to-edge repair vs medical therapy in atrial functional mitral regurgitation: a propensity score-based comparison from the OCEAN-Mitral and REVEAL-AFMR registries 翻译：经导管缘对缘修复术对比药物治疗心房功能性二尖瓣反流：基于OCEAN-Mitral 与REVEAL-AFMR 登记研究的倾向评分比较题目：Pregnancy with a prosthetic heart valve, thrombosis, and bleeding: the ESC EORP Registry of Pregnancy and Cardiac disease III 翻译：人工心脏瓣膜妊娠患者的血栓形成与出血事件：ESC EORP 妊娠与心脏病登记研究Ⅲ 题目：Sex-specific outcomes after transcatheter or surgical treatment of aortic valve stenosis: the DEDICATE-DZHK6 trial 翻译：主动脉瓣狭窄经导管或外科治疗后的性别特异性结局：DEDICATE-DZHK6试验题目：Outcomes of moderate mixed aortic valve stenosis and regurgitation 翻译：中度混合性主动脉瓣狭窄合并关闭不全的临床结局 JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY（本周无更新） 5.胃肠肝病学 LANCET GASTROENTEROLOGY & HEPATOLOGY 题目：Efficacy and safety of subcutaneous guselkumab induction therapy in participants with moderately to severely active ulcerative colitis (ASTRO): a double-blind, treat-through, randomised, placebo-controlled, phase 3 trial 翻译：皮下注射古塞库单抗诱导治疗中重度活动性溃疡性结肠炎的疗效与安全性（ASTRO）：一项双盲、持续给药、随机、安慰剂对照Ⅲ期临床试验题目：Safety, pharmacokinetics, and preliminary efficacy of VS-01, an intraperitoneal liposomal infusion, in patients with decompensated liver cirrhosis, ascites, and covert hepatic encephalopathy: a phase 1b, first-in-human, open-label, non-randomised, single ascending and multiple dose study 翻译：腹腔内脂质体输注药物 VS-01 用于失代偿期肝硬化、腹水及隐匿性肝性脑病患者的安全性、药代动力学与初步疗效：一项Ⅰb期、首次人体、开放标签、非随机、单次及多次剂量递增研究题目：Ileocaecal resection versus infliximab for ileal Crohn's disease: retrospective 10-year follow-up of the LIR!C trial 翻译：回盲部切除术对比英夫利昔单抗治疗回肠克罗恩病：LIR!C试验10 年回顾性随访题目：Long-term oncological outcomes following algorithm-based care versus usual care for the early recognition and management of complications after pancreatic resection: a post-hoc analysis of a nationwide, stepped-wedge cluster-randomised trial 翻译：基于流程化管理对比常规管理用于胰腺切除术后并发症早期识别与处理的长期肿瘤学结局：一项全国性阶梯楔状整群随机试验的事后分析 JOURNAL OF HEPATOLOGY（本周无更新） GUT 题目：Roseburia inulinivoransincreases muscle strength 翻译：菊糖利用罗斯氏菌可增强肌肉力量 GASTROENTEROLOGY（本周无更新） 6.呼吸病学 LANCET RESPIRATORY MEDICINE（本周无更新） EUROPEAN RESPIRATORY JOURNAL（本周无更新） 7.感染与微生物 LANCET INFECTIOUS DISEASES（本周无更新） LANCET MICROBE 题目：Artesunate–pyronaridine–atovaquone–proguanil and artesunate–fosmidomycin–clindamycin compared with standard artesunate–pyronaridine for the treatment of uncomplicated malaria (MultiMal): a randomised, controlled, clinical, phase 2 trial in Gabon and Ghana 翻译：青蒿琥酯–吡咯奈啶–阿托伐醌–氯胍与青蒿琥酯–磷霉素–克林霉素对比标准方案青蒿琥酯–吡咯奈啶治疗单纯性疟疾（MultiMal）：在加蓬与加纳开展的一项随机、对照、Ⅱ期临床试验题目：Efficacy and safety of lenacapavir, teropavimab, and zinlirvimab: week-26 primary outcome results from a multicentre, open-label, randomised, active-controlled, phase 2 study 翻译：来那卡帕韦、替罗帕韦单抗与津利韦单抗的疗效与安全性：一项多中心、开放标签、随机、阳性对照Ⅱ期研究的26 周主要结局结果题目：The effect of pneumococcal conjugate vaccine and pneumococcal polysaccharide vaccine on nasopharyngeal colonisation following human infection challenge with serotype 3 and serotype 6B (PREVENTING PNEUMO 2): a double-masked, randomised, controlled, phase 4 trial 翻译：肺炎球菌结合疫苗与多糖疫苗对 3 型和6B 型肺炎球菌人体攻毒感染后鼻咽部定植的影响（PREVENTING PNEUMO 2）：一项双盲、随机、对照Ⅳ期临床试验题目：Parasite clearance in patients with Plasmodium vivax monoinfection treated with artesunate in Cambodia: an observational secondary analysis of trial data 翻译：柬埔寨单用青蒿琥酯治疗间日疟原虫单一感染患者的寄生虫清除情况：试验数据的观察性二次分析题目：Spatiotemporal patterns of Rift Valley fever virus in Africa: a retrospective genomic epidemiology and phylodynamic modelling study 翻译：非洲裂谷热病毒的时空分布特征：一项回顾性基因组流行病学与系统动力学建模研究题目：Characterisation of Bordetella pertussis virulence and macrolide resistance in Australia by targeted culture-independent sequencing: a genomic epidemiology study 翻译：基于靶向非培养测序的澳大利亚百日咳鲍特菌毒力与大环内酯类耐药特征分析：一项基因组流行病学研究题目：Bedaquiline resistance in patients with Xpert MTB/RIF Ultra-tested rifampicin-resistant tuberculosis in the Western Cape, South Africa: a prospective study 翻译：南非西开普省经 Xpert MTB/RIF Ultra 检测的利福平耐药结核患者中的贝达喹啉耐药情况：一项前瞻性研究题目：Serotype-specific pneumococcal invasiveness: a global meta-analysis of paired estimates of disease incidence and carriage prevalence 翻译：血清型特异性肺炎球菌侵袭性：疾病发病率与携带率配对估计值的全球Meta 分析 NATURE MICROBIOLOGY 题目：HIV-1-encoded circular RNA enhances viral transcription through Tat binding 翻译：HIV‑1 编码的环状RNA 通过结合Tat 增强病毒转录题目：Plasmids promote antimicrobial resistance through insertion sequence-mediated gene inactivation 翻译：质粒通过插入序列介导的基因失活促进耐药性产生题目：Epitope-focused discovery of SARS-CoV-2 antibodies that potently neutralize Omicron variants 翻译：基于表位靶向筛选强效中和奥密克戎变异株的新冠病毒抗体题目：Evolution and spillover dynamics of yellow fever at the forest–urban interface in Brazil 翻译：巴西森林—城市交界地带黄热病的进化与跨物种传播动态题目：Conditional activation of Cas13 enforces lysogeny in a native type VI-A CRISPR host 翻译：Cas13 的条件性激活在天然VI‑A 型CRISPR 宿主中维持溶原状态题目：A clinic-responder-derived defined microbial consortium enhances anti-PD-1 immunotherapy efficacy in mice 翻译：临床应答者来源的明确菌群组合物可增强小鼠抗PD‑1 免疫治疗效果题目：Bacterial Schlafen proteins mediate phage defence 翻译：细菌 Schlafen 蛋白介导噬菌体防御 MICROBIOME 题目：Pilea: profiling bacterial growth dynamics from metagenomes with sketching 翻译：Pilea：基于草图法从宏基因组解析细菌生长动态题目：Host immunogenetic variation and gut microbiome functionality in a wild vertebrate population 翻译：野生脊椎动物种群的宿主免疫遗传变异与肠道微生物组功能题目：Agarose oligosaccharides balance intestinal stem cell homeostasis in aging D. melanogaster by regulating the Acetobacter persici-acetic acid-JAK/STAT signaling axis 翻译：琼脂寡糖通过调控波斯醋酸杆菌–乙酸–JAK/STAT信号轴维持衰老果蝇肠道干细胞稳态题目：Ensemble test for microbiome data 翻译：微生物组数据的整合检验方法题目：The antimicrobial gut resistome of the Wayampi reveals a shared background of antibiotic and metal resistance genes with industrialized populations, underscoring the “robust-yet-fragile” architecture of human gut microbiomes 翻译：瓦亚皮人群肠道抗菌耐药组揭示：其抗生素与金属抗性基因背景与工业化人群共享，凸显人类肠道微生物组“稳健却脆弱”的结构特征 JOURNAL OF INFECTION（本周无更新） 8.公共卫生和流行病学 LANCET PUBLIC HEALTH（本周无更新） LANCET GLOBAL HEALTH（本周无更新） 9.内科学 JAMA INTERNAL MEDICINE（本周无更新） ANNALS OF INTERNAL MEDICINE（本周无更新） 10.血液学 LANCET HAEMATOLOGY（本周无更新） 11.牙科与口腔外科 JOURNAL OF CLINICAL PERIODONTOLOGY 题目：Evaluation of the Accuracy of Infrared Thermographic Imaging for the Diagnosis of Periodontal Diseases: A Cross-Sectional Study 翻译：红外热成像技术诊断牙周疾病准确性的评价：一项横断面研究题目：Dietary Nitrate Intake and 16S rRNA-Inferred Nitrite-Generating Capacity of the Subgingival Microbiome May Influence Glucose Metabolism: Results From the Oral Infections Glucose Intolerance and Insulin Resistance Study (ORIGINS) 翻译：膳食硝酸盐摄入及龈下微生物组 16S rRNA 预测的亚硝酸盐生成能力或影响糖代谢：口腔感染、糖耐量异常与胰岛素抵抗研究（ORIGINS）结果题目：Associations Between Restoration Margins and Adjacent Periodontal Status—Longitudinal Results From SHIP-TREND 翻译：修复体边缘与邻近牙周状况的相关性：SHIP-TREND研究的纵向结果题目：Bone-Level Versus Tissue-Level Titanium Dental Implants: A Comparative Cross-Sectional Study 翻译：骨水平与软组织水平钛牙种植体：一项对比横断面研究题目：Impact of Interdental Brushing on Pregnancy-Associated Gingivitis: A Secondary Analysis of a Randomised Controlled Trial 翻译：牙间刷对妊娠期龈炎的影响：一项随机对照试验的二次分析题目：Adjunctive Systemic Amoxicillin and Metronidazole Following Surgical Peri-Implantitis Treatment: A Single-Blind Randomised Controlled Trial With a 1-Year Follow-Up 翻译：种植体周围炎手术治疗后辅助全身应用阿莫西林+ 甲硝唑：1年随访单盲随机对照试验题目：Outcomes of Active Periodontal Therapy in a Specialist University Setting Following EFP S3 Treatment Guideline in Stage III–IV Periodontitis Patients 翻译：遵循 EFP S3 治疗指南在大学专科诊疗中心对Ⅲ–Ⅳ期牙周炎患者行积极牙周治疗的疗效题目：Clinical Efficacy of Interventions Based on Professional Mechanical Plaque Removal in the Treatment of Dental Biofilm–Induced Gingivitis: A Systematic Review and Meta-Analysis 翻译：基于专业机械性菌斑清除的干预措施治疗牙生物膜诱导性龈炎的临床疗效：系统评价与Meta 分析题目：Serine Promotes Inflammatory Macrophage Polarisation in Periodontitis via NAD+ Signalling 翻译：丝氨酸通过 NAD⁺信号通路促进牙周炎中炎症性巨噬细胞极化题目：Non-Syndromic Hereditary Gingival Fibromatosis Driven by Chymase Deficiency Is Attenuated by Verteporfin-Loaded Exosomes 翻译：糜蛋白酶缺陷所致非综合征型遗传性牙龈纤维瘤病可被载维泊芬外泌体缓解题目：Melatonin Alleviates Periodontitis by Suppressing Neutrophil Extracellular Traps–Dependent Neutrophil Recruitment 翻译：褪黑素通过抑制中性粒细胞胞外诱捕网依赖的中性粒细胞募集减轻牙周炎题目：Tryptophan-Derived Microbial Metabolite Indole-3-Acetic Acid Ameliorates Periodontitis Through AhR/CYP1A1-Mediated Macrophage Polarisation 翻译：色氨酸来源微生物代谢产物吲哚 - 3 - 乙酸通过AhR/CYP1A1 介导的巨噬细胞极化改善牙周炎

2026-03-13

·BE and NTM-PD全程管理

【临床方案】非结核分枝杆菌疾病：新型候选药物和再利用药物开发进展

导读：文章概要这篇发表于《Frontiers in Cellular and Infection Microbiology》2023年的迷你综述，聚焦全球发病率持续攀升的非结核分枝杆菌（NTM）感染治疗困境，核心梳理了新型候选药物与抗结核/抗菌药物重定位在NTM治疗中的研发与应用进展，详细阐述了恶唑烷酮类、四环素类等多类药物的作用机制、体外/体内抗NTM活性、临床应用现状及不良反应，同时介绍了DprE1抑制剂、MmpL3抑制剂等新型复方化合物的研发潜力，指出当前NTM治疗无专属特效药、药物耐药性加剧的问题，强调亟需开展更多临床试验验证候选药物的临床疗效，为NTM治疗药物的研发与临床应用提供了关键参考。一、NTM感染的治疗现状与核心困境 1. 发病率与耐药性双升：全球NTM感染率持续增长，中国分枝杆菌培养阳性标本中NTM分离率从1979年的4.3%升至2010年的22.9%；NTM对多种抗生素天然耐药，尤以脓肿分枝杆菌（Mab）和鸟分枝杆菌复合群（MAC）为甚，二者占NTM肺部疾病（NTM-PD）的90%以上，是临床治疗的主要难点。 2. Mab与MAC的耐药特征： Mab对大环内酯类抗生素（克拉霉素、阿奇霉素）存在诱导性耐药，克拉霉素耐药率达14%~38%，阿奇霉素为10%；MAC治疗成功率仅39%，与广泛耐药结核（XDR-TB）相当，大环内酯类耐药的MAC肺部疾病1年全因死亡率达10%。 3. 无专属特效药，依赖药物重定位：目前尚无针对NTM感染的专属研发药物，美国胸科学会推荐的所有NTM治疗方案均基于现有药物的适应症扩展，抗NTM药物研发高度依赖抗菌药/抗结核药的重定位使用，且最优药物组合尚未明确。二、已重定位应用的抗NTM核心药物类别（一）恶唑烷酮类：蛋白合成抑制剂，覆盖快/慢生长型NTM 1. 作用机制：结合细菌23S核糖体，阻断肽基转移酶中心的tRNA结合，抑制微生物蛋白合成，对革兰氏阳性菌、耐药结核及NTM均有活性。 2. 代表药物与活性：利奈唑胺（LZD）、特地唑胺（TZD）、舒特唑胺（SZD）、德拉唑胺（DZD）均对快速生长型（RGM）和缓慢生长型（SGM）NTM有体外抑制活性，MIC均≤8mg/ml；其中TZD对Mab两个亚种的MIC50/90均为1/2μg/ml，是该类中抗Mab活性最强的药物，SZD对鸟分枝杆菌的抑制活性最优。 3. 临床应用：LZD和TZD已用于MAC、Mab、偶发分枝杆菌等NTM感染治疗，67%的龟分枝杆菌/Mab感染者经LZD方案治疗实现临床治愈，58%的感染者经TZD方案达到相同效果；不良反应主要为骨髓抑制、血液疾病、头痛恶心等，TZD耐受性优于LZD。（二）四环素类：靶向30S核糖体，抗Mab活性突出 1. 作用机制：结合细菌30S核糖体亚基，抑制氨酰tRNA与mRNA-核糖体复合物结合，阻断蛋白合成；新一代药物优化了初代胃肠道不良反应强、死亡率高的缺陷。 2. 代表药物与活性：替加环素（TGC）、依拉环素（ERC）、奥马环素（OMC）对RGM的MIC≤0.5mg/ml，ERC抗Mab活性最优（MIC90=0.25mg/ml），且活性与克拉霉素相当；SAC因活性较弱暂未用于NTM治疗。 3. 临床应用：TGC为指南推荐的Mab感染治疗药物，OMC口服/静脉双途径给药的优势使其成为Mab/龟分枝杆菌感染的潜力药物，46%的Mab-PD患者经OMC方案实现培养阴性，18%达到培养转阴；不良反应以轻中度恶心/呕吐为主，凝血障碍为TGC特有少见不良反应。（三）二芳基喹啉类：ATP合酶抑制剂，广谱抗NTM 1. 作用机制：抑制细菌氧化磷酸化所需的ATP合酶（atpE基因编码的c亚基），阻断能量合成，对分枝杆菌属具有广谱活性。 2. 代表药物与活性：贝达喹啉（BDQ）是核心药物，对几乎所有SGM的MIC<1mg/ml，RGM的MIC≤2mg/ml，对MAC的MIC50/90低至0.015/0.12mg/ml；苏达吡啶（WX-081）为BDQ衍生物，安全性更优（对QTc间期影响小），但抗NTM活性略低于BDQ。 3. 临床应用：BDQ已用于Mab、MAC、偶发分枝杆菌等难治性NTM感染，60%的晚期NTM-PD患者经BDQ方案实现微生物学应答，是目前重定位药物中抗NTM谱最广的药物；不良反应为头痛、头晕、呕吐、关节痛。（四）硝基咪唑类：细胞壁合成抑制剂，靶向堪萨斯分枝杆菌 1. 作用机制：抑制分枝杆菌霉菌酸生物合成，阻断细胞壁生成，主要对结核分枝杆菌有强效杀菌活性。 2. 代表药物与活性：德拉马尼（DLM）、普托马尼（PRE）对SGM活性差异大，对堪萨斯分枝杆菌的MIC50/90低至0.25/1mg/ml，为强效抑制；但对Mab、MAC等主流致病性NTM的MIC>16μg/ml，几乎无抑制活性。 3. 临床应用：目前尚未用于临床NTM治疗，仅为耐药堪萨斯分枝杆菌感染的潜在候选药物；DLM易引发QT间期延长，PRE的不良反应以呕吐、痤疮、转氨酶升高等为主。（五）氯法齐明（CFZ）：膜靶向药物，广谱抗NTM且临床应用成熟 1. 作用机制：靶点尚未完全明确，推测主要作用于细菌细胞膜，为疏水性利福平吩嗪类药物，兼具抗麻风、结核和NTM活性。 2. 体外活性：对多数SGM的MIC<1mg/ml，Mab临床分离株70%的MIC≤1.5mg/ml；为MAC、Mab的流行病学折点（ECOFF）分别为1mg/ml、2mg/ml。 3. 临床应用：目前临床应用最广泛的重定位抗NTM药物，覆盖Mab、MAC、龟分枝杆菌等多种NTM，约50%的感染者经CFZ方案实现治疗成功，其中Mab感染者的成功率达63%；二期临床试验正在评估其对MAC-PD的疗效。不良反应为皮肤色素沉着、胃肠道紊乱、QT间期延长。三、具研发潜力的新型复方化合物此类药物多为抗结核新型候选药，针对NTM的细胞壁合成、拓扑异构酶等靶点，体外/动物实验显示出良好抗NTM活性，部分已进入临床试验阶段，是未来NTM专属药物研发的核心方向。 1. DprE1抑制剂：靶向分枝杆菌细胞壁合成关键酶DprE1，OPC-167832为代表，对Mab的体外MIC为2.37~6.85mg/ml，小鼠结核模型中单药/联合用药均显效，是Mab感染的潜力候选药；其余如BTZ-043、TBA-7371对NTM无活性。 2. SPR720（SPR719前药）：靶向DNA促旋酶ATP酶亚基，抑制细菌DNA复制，对RGM的MIC50为0.06~4mg/ml，MAC的MIC90≤2mg/ml；小鼠模型中可降低Mab/MAC载量，已获FDA孤儿药资格，进入NTM-PD的IIa期临床试验。 3. GSK286：亮氨酰-tRNA合成酶抑制剂，对Mab的MIC90低至0.063mg/ml，体外活性极强，但对MAC无抑制作用，目前处于结核治疗的IIa期临床试验。 4. 吲哚-2-甲酰胺衍生物（ICs）：抑制霉菌酸转运蛋白MmpL3，阻断细胞壁外膜的海藻糖单霉菌酸转运，两个先导化合物对Mab的MIC=0.125μg/ml，体外杀菌活性显著。 5. 哌啶醇类化合物（PIPD1）：抑制海藻糖单霉菌酸转运，破坏阿拉伯半乳聚糖的霉菌酰化，对Mab的MIC=0.125μg/ml，且在巨噬细胞和斑马鱼模型中可显著降低细菌载量、提高存活率，抗Mab活性突出。四、NTM药物研发的关键问题与未来方向（一）现有研发与应用的核心局限 1. 临床证据不足：多数药物的抗NTM活性仅停留在体外/动物实验阶段，临床数据多为病例报告或小样本研究，缺乏大样本、随机对照试验验证疗效与安全性。 2. 药物不良反应限制：部分核心药物（如LZD的骨髓抑制、CFZ的皮肤色素沉着、DLM的QT间期延长）的不良反应限制了长期使用，而NTM治疗周期长，耐受性成为关键问题。 3. 耐药性潜在风险：重定位药物的长期使用已出现诱导性耐药（如Mab对大环内酯类的erm(41)基因介导耐药），新型化合物尚未开展耐药性监测研究。 4. 给药途径单一：多数药物以静脉给药为主，口服药物种类少，难以满足NTM长期居家治疗的需求。（二）未来研发与临床应用重点 1. 推进临床试验：加快OPC-167832、SPR720等新型化合物的临床研究，同时开展重定位药物的联合用药试验，明确最优治疗方案。 2. 优化药物剂型：开发口服、吸入型制剂（如CFZ吸入混悬液），提高药物在肺部的局部浓度，降低全身不良反应。 3. 探索新型治疗策略：噬菌体疗法在NTM感染中显示出良好的安全性和有效性，且未发现噬菌体耐药，可作为药物治疗的辅助策略。 4. 聚焦靶点研发：针对NTM的特有靶点（如MmpL3、DprE1）研发专属药物，突破“重定位依赖”的研发困境，从根源上解决天然耐药问题。 5. 耐药监测体系建立：建立全球NTM耐药监测网络，及时掌握耐药谱变化，为药物研发和临床用药调整提供依据。五、总结 NTM感染的全球流行与耐药性加剧使其成为重要的公共卫生问题，而无专属特效药和药物组合不明确是当前治疗的核心痛点。抗结核药和抗菌药的重定位使用成为现阶段NTM治疗的主要手段，其中恶唑烷酮类、四环素类、贝达喹啉和氯法齐明因广谱的抗NTM活性和成熟的临床数据，成为临床一线选择。同时，DprE1抑制剂、MmpL3抑制剂、SPR720等新型复方化合物在体外/动物实验中展现出优异的抗NTM活性，部分已进入临床试验，为NTM专属药物研发带来了新突破。未来，NTM药物研发需以临床试验验证为核心，结合新型靶点挖掘、剂型优化和联合用药策略，同时探索噬菌体疗法等新型辅助手段，才能逐步解决耐药性和治疗效果不佳的问题，最终改善NTM感染者的临床结局。参考文献： Non-tuberculous mycobacterial disease: progress and advances in the development of novel candidate and repurposed drugs. 期刊：Frontiers in cellular and infection microbiology 日期：2023-10-02 DOI ：10.3389/fcimb.2023.1243457

微生物疗法临床研究临床结果

100 项与富马酸贝达喹啉相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09873	富马酸贝达喹啉	J04AK05	DB08903

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
肺结核	日本	Janssen Pharmaceutical KK	2018-01-19
结核	韩国	Janssen Korea Ltd.	2014-03-21
多重耐药性肺结核	欧盟	Janssen-Cilag International NV	2014-03-05
多重耐药性肺结核	冰岛	Janssen-Cilag International NV	2014-03-05
多重耐药性肺结核	列支敦士登	Janssen-Cilag International NV	2014-03-05
多重耐药性肺结核	挪威	Janssen-Cilag International NV	2014-03-05
耐多药结核病	美国	Janssen Therapeutics, Inc.	2012-12-28

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
细胞内鸟分枝杆菌感染	临床3期	日本	Janssen Pharmaceuticals, Inc.	2021-01-08
细胞内鸟分枝杆菌感染	临床3期	韩国	Janssen Pharmaceuticals, Inc.	2021-01-08
细胞内鸟分枝杆菌感染	临床3期	中国台湾	Janssen Pharmaceuticals, Inc.	2021-01-08
肺部感染	临床3期	爱沙尼亚	Janssen Infectious Diseases-Diagnostics BV	2012-06-13
广泛耐药结核病	临床3期	立陶宛	Janssen Infectious Diseases-Diagnostics BV	2011-09-16
麻风结节性红斑	临床2期	巴西	Janssen Research & Development LLC	2018-09-26
多菌麻风	临床2期	巴西	Janssen Research & Development LLC	2018-09-26
HIV感染	临床1期	-	Tibotec Virco Virology BV	2009-02-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NTBERC (ATS2025)	N/A	利福平耐药结核病	-	Bedaquiline	廠築鏇鬱鑰願鹹獵積構(糧糧繭壓醖觸齋憲觸顧) = 淵蓋壓齋憲鑰鹽壓觸蓋壓觸餘觸襯遞願簾襯積 (鏇鏇網衊簾醖淵衊選築 )	积极	2025-05-16
				Delamanid	廠築鏇鬱鑰願鹹獵積構(糧糧繭壓醖觸齋憲觸顧) = 衊願憲鏇壓蓋憲醖顧齋壓觸餘觸襯遞願簾襯積 (鏇鏇網衊簾醖淵衊選築 )
NCT03474198 (TRUNCATE-TB, Pubmed \| Lancet Infect Dis)	临床2/3期	肺结核	675	Standard Treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol)	齋積願網簾築選膚選廠(膚憲鏇夢繭淵齋繭積鏇) = 餘膚網鬱選築醖製觸鏇繭獵觸鏇壓製獵鹽積鹹 (餘鑰選鹹壓鹹齋艱觸構 ) 更多	不佳	2025-05-01
				High-dose rifampicin and linezolid	齋積願網簾築選膚選廠(膚憲鏇夢繭淵齋繭積鏇) = 淵網積選顧糧襯衊築鏇繭獵觸鏇壓製獵鹽積鹹 (餘鑰選鹹壓鹹齋艱觸構 ) 更多
CTRI/2021/03/032189 (Pubmed \| Clin Infect Dis)	临床3期	多重耐药性肺结核	403	Linezolid 600mg for 26 weeks	獵窪膚範醖鏇餘膚齋醖(範製積積鑰艱範觸襯淵) = 觸簾積簾構願範觸淵鹹膚醖蓋齋築選艱選鏇積 (網觸範淵壓簾齋醖齋憲 ) 更多	积极	2024-12-17
				Linezolid 600mg for 9 weeks followed by 300mg for 17 weeks	獵窪膚範醖鏇餘膚齋醖(範製積積鑰艱範觸襯淵) = 鹹齋構齋製築鹽襯蓋窪膚醖蓋齋築選艱選鏇積 (網觸範淵壓簾齋醖齋憲 ) 更多
ERS2024	N/A	耐药结核病	100	Long oral regimens (Bdq+Lfx or Mfx+Lzd+Cfz+Cs in n=73, Bdq+Lzd+Cfz+Cs+Dlm in n=7, Bdq+Lzd+Cfz+Cs+E in n=3)	鹹簾齋衊觸憲製襯齋繭(網鑰壓簾膚齋膚壓簾襯) = 衊顧製範膚顧淵顧繭鬱網鹽簾繭淵觸願齋膚願 (積觸獵觸鏇膚繭築齋網 ) 更多	不佳	2024-09-07
				Short oral regimen (4 months of Bdq+Hh+Eto+Cfz+Lfx+Z+E followed by 5 months of Cfz+Lfx+Z+E)	鹹簾齋衊觸憲製襯齋繭(網鑰壓簾膚齋膚壓簾襯) = 製願襯艱憲獵願構憲壓網鹽簾繭淵觸願齋膚願 (積觸獵觸鏇膚繭築齋網 ) 更多
ERS2024	N/A	-	58	bedaquiline+delamanid+clofazimine+pyrazinamide (24-36 weeks)	壓艱憲醖鹹製鑰築鑰廠(積鹹醖觸壓蓋構壓壓齋) = 獵糧構糧齋觸築鬱積襯鹹齋選齋繭鹽願壓鏇襯 (艱鏇鹽選構積壓醖構鹹 ) 更多	积极	2024-09-07
				18-20 months WHO-recommended regimen	壓艱憲醖鹹製鑰築鑰廠(積鹹醖觸壓蓋構壓壓齋) = 範築膚鬱窪積願繭艱選鹹齋選齋繭鹽願壓鏇襯 (艱鏇鹽選構積壓醖構鹹 ) 更多
NCT03338621 (SimpliciTB, Pubmed \| Lancet Infect Dis)	临床2期	肺结核	455	Bedaquiline-pretomanid-moxifloxacin-pyrazinamide (BPaMZ) 4 months	夢繭範鹽範築醖鹹鬱積(鑰獵願艱觸鹹鏇壓網醖) = three participants [1%] 鬱鬱餘壓鹽獵獵衊鬱顧 (選顧範糧襯簾鏇鏇壓襯 ) 更多	积极	2024-09-01
NCT05406479 (BE-PEOPLE P2, CTgov)	临床2期	麻风	313	Bedaquiline+BE-PEP (BE-PEP (Bedaquiline Post-Exposure Prophylaxis))	鑰範膚繭糧夢膚觸艱簾(艱衊簾糧衊齋選齋糧繭) = 憲觸願鏇憲製鑰壓選夢鏇糧壓範糧糧齋膚壓窪 (繭構構鹹顧積餘鬱膚鏇, 選鏇餘網觸醖憲襯簾鑰 ~ 鑰鑰壓築願鏇艱鬱網鬱) 更多	-	2024-08-28
				SDR-PEP (SDR-PEP (Single-Dose Rifampicin Post-Exposure Prophylaxis))	鑰範膚繭糧夢膚觸艱簾(艱衊簾糧衊齋選齋糧繭) = 願餘蓋夢壓蓋憲壓窪積鏇糧壓範糧糧齋膚壓窪 (繭構構鹹顧積餘鬱膚鏇, 願膚窪積製鏇鹽齋網艱 ~ 襯夢窪齋遞選鏇艱願齋) 更多
NCT02589782 (TB-PRACTECAL, Pubmed) 人工标引	临床2/3期	广泛耐药结核病	552	rifampicin (Standard care)	鏇艱齋壓繭鹽憲襯夢淵(範鑰鏇鏇鹽遞廠壓繭襯) = 願鏇鑰餘願衊繭鏇範憲艱膚糧醖糧築製簾齋齋 (鹹遞鬱製廠觸顧簾遞膚 ) 更多	积极	2024-02-01
				rifampbedaquilinepretomanidlinezolidmoxifloxacin (BPaLM)	鏇艱齋壓繭鹽憲襯夢淵(範鑰鏇鏇鹽遞廠壓繭襯) = 夢齋遞壓壓築顧獵網壓艱膚糧醖糧築製簾齋齋 (鹹遞鬱製廠觸顧簾遞膚 ) 更多
NCT03896685 (endTB-Q, Pubmed)	临床3期	耐多药结核病	324	Bedaquiline, Linezolid, Clofazimine, Delamanid	鏇網鬱淵願淵鏇廠餘鬱(廠艱蓋構積艱齋積簾範) = 壓範繭築顧鑰淵願鬱鏇膚鏇構鑰糧獵遞顧繭衊 (獵構衊鏇醖窪積淵鬱鹹 )	积极	2023-11-30
				Contemporaneous WHO standard of care for pre-XDR TB	鏇網鬱淵願淵鏇廠餘鬱(廠艱蓋構積艱齋積簾範) = 鹽淵艱築鏇顧製夢衊蓋膚鏇構鑰糧獵遞顧繭衊 (獵構衊鏇醖窪積淵鬱鹹 )
ERS2023	N/A	耐药结核病	16	Bedaquiline-Pretomanid-Linezolid (BPaL) regimens (Pre-XDR-TB)	網鹹廠顧鑰鏇鏇獵網獵(鏇觸壓夢網簾廠觸鏇廠) = 鹽壓顧遞獵願積築廠製網艱齋鑰壓鑰餘製鹽繭 (繭網鑰夢衊蓋製醖醖襯 ) 更多	积极	2023-09-09