The purpose of this study is to support the clinical validation of a new assay to measure the levels of ivacaftor, tezacaftor, and elexacaftor (the components of Trikafta) in the bloodstream in order to achieve greater understanding of the effectiveness of this medication in all people with cystic fibrosis. Blood will be drawn at 3.0, 4.5, and 6.0 hours after taking the medication in the morning.

开始日期2023-02-09

申办/合作机构

National Jewish Health, Inc.

NCT05675592

/ RecruitingN/AIIT

Linking Elexacaftor/Tezacaftor/Ivacaftor to Infections in Cystic Fibrosis Lung Disease

The goal of this observational study o is to define whether, how and to what extent treatment with Trikafta/Kaftrio directly affects Pseudomonas aeruginosa in individuals with cystic fibrosis. The main questions it aims to answer are:
* whether Trikafta/Kaftrio affects the bacterial phenotypes and susceptibility to antibiotics;
* whether Trikafta/Kaftrio impacts the bacterial virulence. Participants will be asked the permission to store and analyze P. aeruginosa isolates collected from respiratory samples for usual care plans before the initiation of treatment with Trikafta/Kaftrio and after 12 and 18 months of treatment. The results of bacterial analysis will be matched with clinical data at the specific time-points.
We expect to define effects of Trikafta/Kaftrio on P. aeruginosa and identify bacterial phenotypes as possible risk factors for its efficacy.

开始日期2022-02-22

申办/合作机构

Ospedale San Raffaele Srl

[+2]

DRKS00023862

/ CompletedN/A

Impact of CFTR-modulation with elexacaftor/tezacaftor/ivacaftor on the exercise capacity, intestinal and respiratory microbiome, microbial and inflammatory metabolites in cystic fibrosis - IMMProveCFInflammation, Microbiome, Metabolome and physical Performance in Cystic Fibrosis

开始日期2021-05-04

申办/合作机构-

100 项与 Elexacaftor 相关的临床结果

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100 项与 Elexacaftor 相关的转化医学

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100 项与 Elexacaftor 相关的专利（医药）

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1,120

项与 Elexacaftor 相关的文献（医药）

2026-12-31·Pulmonology

Treatment adherence and mental health in people with cystic fibrosis and advanced lung disease treated with elexacaftor/tezacaftor/ivacaftor

Article

作者: Bresci, Silvia ; Malanima, Marco Andrea ; Quittner, Alexandra L. ; Graziano, Sonia ; Teodori, Caterina ; Presti, Santiago ; Fevola, Cristina ; Avarello, Angelo ; Lucenteforte, Ersilia ; Castaldo, Alice ; Terlizzi, Vito

INTRODUCTION:

Advanced lung disease (ALD) is a leading cause of mortality in cystic fibrosis (CF). Although Elexacaftor/Tezacaftor/Ivacaftor (ETI) provides significant clinical benefits, little is known about long-term adherence, health-related quality of life (HRQoL), and neuropsychological side-effects in people with CF (PWCF) and ALD. This study evaluated adherence, HRQoL, mental health, and ETI-related side-effects.

METHODS:

In this longitudinal study, PWCF and ALD enrolled in an ETI compassionate use program were assessed cross-sectionally after approximately 30 months of ETI therapy using the Treatment Adherence Questionnaire-CF (TAQ-CF), CFQ-R, PHQ-9, GAD-7, and an ad-hoc neuropsychological side-effects survey. Clinical parameters (ppFEV1, BMI, sweat chloride) and CFQ-R scores were followed from baseline to 36 months.

RESULTS:

Thirty-three PWCF and ALD were included. From baseline to 36 months, sweat chloride decreased by 57.4 mmol/L, while ppFEV1 and BMI increased by 19.4% and 1.6 kg/m², respectively. HRQoL improved significantly across most CFQ-R domains. Mean overall adherence was 75.6%; 45.2% of participants reported high and 51.6% moderate adherence. No significant associations were found between adherence and clinical or mental health outcomes. Concentration difficulties and insomnia were reported by 25.8% and 32.3% of participants, respectively. Anxiety was associated with memory and concentration difficulties and insomnia.

CONCLUSION:

Approximately 30 months after ETI initiation, PWCF and ALD maintained moderate-to-high adherence, potentially reflecting disease severity and treatment burden. ETI provided sustained pulmonary and HRQoL benefits, although persistent neuropsychological side-effects occurred in a subset of participants and were associated with anxiety. Comprehensive ALD management should address both physical and mental health.

2026-12-01·MAGNETIC RESONANCE IN MEDICINE

Adapted Linear Binning Method to Assess Pulmonary Ventilation and Perfusion in Children Using Lung Matrix Pencil Decomposition ( MP )‐ MRI

Article

作者: Curdy, Marion ; Kieninger, Elisabeth ; Latzin, Philipp ; Streibel, Carmen ; Bauman, Grzegorz ; Bieri, Oliver ; Ebner, Lukas ; Wyler, Florian

ABSTRACT:

Purpose:

To adapt and validate a linear binning technique, developed for hyper‐polarized 129Xe MRI, for functional lung MRI with matrix‐pencil decomposition (MP)‐MRI.

Methods:

First, a dedicated normalization was applied to the perfusion‐weighted and the ventilation‐weighted map histograms. Then, using 154 MP‐MRI scans of healthy children, reference bins were defined around the peak of the averaged histogram as normal (±1 SD), high (> 1 SD), low (between −1 SD and −2 SD), and defect (< −2 SD), and subsequently applied to a validation dataset comprising healthy children (HC, N = 41) and children with cystic fibrosis (CF, N = 30) to evaluate the accuracy of the classification and its discriminatory power. Furthermore, a third dataset comprising children with CF pre and post elexacaftor/tezacaftor/ivacaftor (ETI) therapy ( N = 24) was binned to evaluate the method's sensitivity to treatment effects. Standard outcome parameters, computed with a median threshold, served as a comparison.

Results:

The adapted linear binning resulted in significantly higher defect and low percentages for perfusion and ventilation between children with CF and HC ( p values < 0.0001) with high discrimination (AUCs > 0.85). This was comparable to the standard median‐threshold method. Two illustrative cases were included to demonstrate the complementary granularity of the linear binning method. Although standard thresholding indicated improvement in both ventilation and perfusion defects pre and post ETI, linear binning showed that perfusion improvement was restricted to the low category.

Conclusion:

A linear binning method for MP‐MRI was developed and validated, providing a healthy reference based on a large dataset and advancing functional lung image processing.

2026-11-01·CURRENT OPINION IN PULMONARY MEDICINE

Medical issues and pulmonary outcomes in cystic fibrosis and bronchiectasis

Review

作者: Jain, Raksha ; Doumat, George ; Iyer, Manya

Purpose of review:

Bronchiectasis from cystic fibrosis and noncystic fibrosis causes include a spectrum of chronic suppurative airway conditions that share key pathophysiologic mechanisms but differ substantially in genetic basis, epidemiology, and clinical course. Recent therapeutic advances, particularly highly effective CFTR modulators in cystic fibrosis and emerging anti-inflammatory therapies in bronchiectasis, have reshaped disease management and prompted re-evaluation of treatment paradigms, outcome measures, and approaches to long-term monitoring.

Recent findings:

In cystic fibrosis, highly effective CFTR modulator therapy, including elexacaftor/tezacaftor/ivacaftor and the recently approved once daily vanzacaftor/tezacaftor/deutivacaftor, has produced sustained increase in lung function, reduced frequency of pulmonary exacerbations, and improved quality of life, while highlighting the limitations of FEV 1 as a sole future marker of treatment response. In noncystic fibrosis bronchiectasis, the phase 3 ASPEN trial demonstrated that brensocatib, a dipeptidyl peptidase-1 inhibitor, significantly reduces exacerbation frequency and slows lung function decline at the higher dose, representing a potential disease-modifying therapy. Emerging evidence also underscores the prognostic importance of comorbidities and disease modifiers, including Pseudomonas aeruginosa and gastroesophageal reflux disease.

Summary:

Management of all forms of bronchiectasis is increasingly shifting toward individualized, endotype-directed care. Integration of disease-modifying therapies, systematic assessment of comorbidities, validated severity stratification tools, and patient-reported outcomes will be essential to optimizing long-term clinical outcomes and advancing precision medicine approaches across this heterogeneous disease spectrum.

188

项与 Elexacaftor 相关的新闻（医药）

2026-10-12

·BioSpace

Vertex to Present New Data on ALYFTREK® at the North American Cystic Fibrosis Conference

- Data on ALYFTREK in children ages 2 to 5 years demonstrate recovery of pancreatic function in some children – - Additional abstracts on clinical and real-world evidence on CFTR modulators also presented - BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced new interim data from the ALYFTREK ® (vanzacaftor/tezacaftor/deutivacaftor) 2 to 5 years old open-label extension study, highlighting recovery of exocrine pancreatic function in some children in that age group, allowing those children to discontinue pancreatic enzyme replacement therapy (PERT). Pancreatic exocrine insufficiency in children with cystic fibrosis (CF) was previously believed to be irreversible. These data were presented at the North American Cystic Fibrosis Conference (NACFC). “The data presented at NACFC underscore the safety and efficacy of our CF medicines in the real world and in clinical trials in younger age groups. The data from the Phase 3 open-label study in 2 to 5 year olds evaluating exocrine pancreatic function represent a profound shift in how we understand the benefits of treating cystic fibrosis in its earliest stages,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “For decades, pancreatic organ failure and resulting exocrine pancreatic insufficiency has been accepted as an irreversible consequence of CF, but these remarkable data in younger children treated with ALYFTREK show that, in fact, pancreatic failure can be reversed.” ALYFTREK interim data on exocrine pancreatic function Presented as a late breaker poster at NACFC, the new interim data from 48 children who enrolled in a PERT discontinuation substudy VX22-121-106 (Study 106) Cohort 2, an ongoing open-label extension study of vanzacaftor/tezacaftor/deutivacaftor in children 2 to 5 years of age, demonstrate that early intervention with vanzacaftor/tezacaftor/deutivacaftor has a positive impact on exocrine pancreatic insufficiency (EPI) and can help achieve PERT independence. EPI is one of the earliest and most severe manifestations of CF, occurring in ~90% of children during the first year of life, requiring lifelong treatment, and driving serious downstream comorbidities. Specifically, data from the interim analysis conducted after children received at least 48 weeks of vanzacaftor/tezacaftor/deutivacaftor treatment showed: Meaningful improvement in fecal elastase-1 (FE-1) levels demonstrates restored pancreatic function: Mean FE-1, a well-established endpoint of exocrine pancreatic function, was 239.7 μg/g, representing a mean increase of 110.2 µg/g from baseline, with nearly half (48.6%) of children reaching the pancreatic sufficiency threshold of ≥200 µg/g. Of the 48 children eligible for the PERT discontinuation substudy, 18 (37.5%) successfully discontinued PERT for a mean duration of 8.6 weeks (range: 1.9 to 17.6 weeks) at the time of the interim data analysis. Additionally, 7 participants had discontinued PERT prior to the substudy eligibility. Across the full enrolled cohort of 66 children, 50% were not on PERT at the time of the data cut. The ability to discontinue PERT suggests reversal of prior pancreatic exocrine organ failure for those participants. The use of ALYFTREK in children with CF 2 to 5 years old is investigational. Additional data presented at NACFC from October 7-10 in Atlanta, Georgia Vertex also presented the following abstracts on clinical and real-world evidence on CFTR modulators as listed below. These abstracts are published in the Journal of Cystic Fibrosis : “Long-term benefits of VNZ/TEZ/D-IVA in reducing IV antibiotic use in people with CF aged 12 years and older: Post-hoc analyses of 96-week open-label extension analysis” “Natural history study of exocrine pancreatic function in infants with cystic fibrosis less than 12 months of Age” “Lifetime treatment burden and cost of PERT among people with cystic fibrosis” U.S. IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR ALYFTREK AND TRIKAFTA INDICATIONS AND USAGE ALYFTREK is indicated for the treatment of patients ≥6 years who have a clinical diagnosis of cystic fibrosis (CF) and ≥1 variant in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive based on clinical and/or in vitro data or results in CFTR protein production.* TRIKAFTA is indicated for the treatment of patients ≥2 years who have a clinical diagnosis of CF and ≥1 variant in the CFTR gene that is responsive based on clinical and/or in vitro data or results in CFTR protein production.* *If the patient’s genotype is unknown, an FDA-cleared CF genetic test should be used to confirm the presence of ≥1 indicated variant. IMPORTANT SAFETY INFORMATION BOXED WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE Elevated transaminases have been observed in patients treated with ALYFTREK. TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Cases of liver failure leading to transplantation and death have been reported in both clinical trials and the postmarketing setting in patients with and without a history of liver disease taking TRIKAFTA, a fixed-dose combination drug containing elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA), the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA. Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating ALYFTREK or TRIKAFTA, then every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or liver function test (LFT) elevations at baseline. Interrupt ALYFTREK or TRIKAFTA for significant elevations in LFTs or in the event of signs or symptoms of liver injury. Consider referral to a hepatologist. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, resume treatment only if benefit is expected to outweigh risk. Closer monitoring is advised after resuming treatment. ALYFTREK or TRIKAFTA should not be used in patients with severe hepatic impairment (Child-Pugh Class C). ALYFTREK or TRIKAFTA is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B). ALYFTREK or TRIKAFTA should only be considered when there is a clear medical need and benefit outweighs risk. If ALYFTREK is used, monitor patients closely. If TRIKAFTA is used, use with caution at a reduced dosage and monitor patients closely. WARNINGS AND PRECAUTIONS DRUG-INDUCED LIVER INJURY AND LIVER FAILURE Elevated transaminases have been observed in patients treated with ALYFTREK. TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Liver failure leading to transplantation and death has been reported in patients with and without a history of liver disease taking TRIKAFTA. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA Assess LFTs in all patients prior to initiating ALYFTREK or TRIKAFTA, then every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or LFT elevations at baseline, or a history of elevated LFTs with drugs containing ELX, TEZ, and/or IVA Interrupt ALYFTREK or TRIKAFTA in the event of signs or symptoms of liver injury, which may include: Significant elevations in LFTs (e.g., ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN) Clinical symptoms suggestive of liver injury (e.g., jaundice, right upper quadrant pain, nausea, vomiting, altered mental status, ascites) Consider referral to a hepatologist and follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, and if benefit is expected to outweigh risk, resume treatment with close monitoring ALYFTREK and TRIKAFTA should not be used in patients with severe hepatic impairment, are not recommended in patients with moderate hepatic impairment, and should only be considered when there is a clear medical need and benefit outweighs risk. If ALYFTREK is used, monitor patients closely. If TRIKAFTA is used, use with caution at a reduced dosage and monitor patients closely HYPERSENSITIVITY REACTIONS, INCLUDING ANAPHYLAXIS Hypersensitivity reactions, including cases of angioedema and anaphylaxis, have been reported in the postmarketing setting for TRIKAFTA. If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue ALYFTREK or TRIKAFTA and institute appropriate therapy. Consider benefits and risks to determine whether to resume treatment PATIENTS WHO DISCONTINUED OR INTERRUPTED ELX-, TEZ-, OR IVA-CONTAINING DRUGS DUE TO ADVERSE REACTIONS ALYFTREK There are no available safety data for ALYFTREK in patients who previously discontinued or interrupted treatment with drugs containing ELX, TEZ, or IVA due to adverse reactions. Consider benefits and risks before using ALYFTREK in these patients and if used, closely monitor for adverse reactions INTRACRANIAL HYPERTENSION (IH) IH has been reported in the postmarketing setting with TRIKAFTA, which contains the same or similar active ingredients as ALYFTREK. Clinical manifestations of IH include headache, blurred vision, diplopia, and potential vision loss; papilledema can be found on fundoscopy. If an unusual headache or visual disturbances occur during treatment, and IH is suspected, interrupt treatment and refer for prompt medical evaluation. Consider benefits and risks to determine whether to resume treatment. Patients should be monitored until IH resolution and for recurrence. Patients with elevated vitamin A levels may be at increased risk NEUROPSYCHIATRIC EVENTS, INCLUDING SUICIDAL THOUGHTS AND BEHAVIORS Serious neuropsychiatric events, including symptoms of anxiety, depression, suicidal ideation and behavior, and sleep disturbances, have been reported in the postmarketing setting in patients with and without a previous history of neuropsychiatric symptoms taking ALYFTREK or TRIKAFTA. Symptoms may occur within the first 3 months of treatment. Assess patients for baseline neuropsychiatric symptoms and monitor for new or worsening symptoms. Consider the benefits and risks to determine if treatment should be interrupted at symptom occurrence or resumed with symptom improvement DRUG INTERACTIONS Use With CYP3A Inducers Following concomitant use of strong or moderate CYP3A inducers with ALYFTREK, exposures of vanzacaftor, TEZ, and deutivacaftor were decreased, which may reduce ALYFTREK effectiveness. Concomitant use with strong or moderate CYP3A inducers is not recommended Exposure to IVA is significantly decreased and exposure to ELX and TEZ are expected to decrease with concomitant use of CYP3A inducers, which may reduce effectiveness of TRIKAFTA. Concomitant use with strong CYP3A inducers is not recommended Use With CYP3A Inhibitors Exposure to vanzacaftor, TEZ, and deutivacaftor or ELX, TEZ, and IVA are increased when used concomitantly with strong or moderate CYP3A inhibitors. The dose of ALYFTREK or TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors CATARACTS Non-congenital lens opacities have been reported in pediatric patients treated with TRIKAFTA, which contains IVA (similar to an active ingredient in ALYFTREK). Baseline and follow-up ophthalmological examinations are recommended in pediatric patients ADVERSE REACTIONS ALYFTREK Serious adverse reactions that occurred more frequently with ALYFTREK than with ELX/TEZ/IVA in 2 or more patients (≥0.4%) were influenza (1.5%), increased AST (0.4%), increased GGT (0.4%), depression (0.4%), and syncope (0.4%) The most common adverse reactions occurring in ≥5% of patients and at a frequency higher than ELX/TEZ/IVA by ≥1% were cough, nasopharyngitis, upper respiratory tract infection (URTI), headache, oropharyngeal pain, influenza, fatigue, increased ALT and AST, rash, and sinus congestion TRIKAFTA Serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo included rash (1% vs <1%) and influenza (1% vs 0%) The most common adverse reactions occurring in ≥5% of patients treated with TRIKAFTA and at a rate higher than placebo by ≥1% were headache; URTI; abdominal pain; diarrhea; rash; increased ALT, blood creatine phosphokinase, AST, and blood bilirubin; nasal congestion; rhinorrhea; rhinitis; influenza; sinusitis; and constipation USE IN SPECIFIC POPULATIONS PEDIATRIC USE Safety and effectiveness have not been established for ALYFTREK in patients <6 years, nor for TRIKAFTA in patients <2 years. The use in children under these ages is not recommended Please see full Prescribing Information, including Boxed WARNING , for ALYFTREK and TRIKAFTA . About Cystic Fibrosis Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 112,000 people, including approximately 97,000 people in the United States, Europe, Australia and Canada. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain variants in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the 30s, but with treatment, projected survival is improving. Learn more about the importance of sweat chloride (SwCl) in cystic fibrosis. As of today, our CF medicines are available in more than 80 countries across six continents, treating more than 80,000 people with CF. This represents the vast majority of known patients diagnosed with CF, and we are committed to expanding access even further. About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases and conditions. The company has approved therapies for cystic fibrosis, sickle cell disease, transfusion-dependent beta thalassemia, acute pain and acromegaly, and it continues to advance clinical and research programs in these areas. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including IgA nephropathy, neuropathic pain, APOL1-mediated kidney disease, primary membranous nephropathy, congenital adrenal hyperplasia, ACTH-dependent Cushing's syndrome, autosomal dominant polycystic kidney disease, type 1 diabetes, generalized myasthenia gravis, and myotonic dystrophy type 1. Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 16 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit or follow us on LinkedIn , Facebook , Instagram , YouTube and X . Special Note Regarding Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, the statements made by Carmen Bozic, M.D., statements regarding expectations for the clinical benefits of ALYFTREK, statements about Vertex’s commitment to further expand access to its CF medicines, and expectations for the data presented at NACFC. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's research and development programs may not support registration or further development of its potential medicines in a timely manner, or at all, due to safety, efficacy, and other risks listed under the heading “Risk Factors” in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at and available through the company's website at . You should not place undue reliance on these statements, or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available. (VRTX-GEN) Contacts Vertex Pharmaceuticals Incorporated Investors: InvestorInfo@vrtx.com Media: mediainfo@vrtx.com or U.S.: 617-341-6992

临床结果临床3期

2026-10-06

·微信

临床微生物学与感染 32卷 7-10期、7期增刊

Clinical Microbiology and Infection[Jour] AND 32[volume] AND 7[issue] 临床微生物学与感染 32卷 7期 https://www.sciencedirect.com/journal/clinical-microbiology-and-infection/vol/32/issue/7 Editorial Note（编者注） 1 Call for editor in virology 病毒学编辑征稿启事 J. Rodríguez-Baño Page 1035 Commentaries（述评） 2 US WHO withdrawal and clinical readiness 美国退出世卫组织与临床应对准备 Lukasz Szarpak, Michal Pruc, Beata Piskorska, Maciej Maslyk Pages 1036-1038 3 Reunion's bold bet against leptospirosis 留尼汪岛抗击钩端螺旋体病的大胆举措 Anissa Desmoulin, Xavier Deparis, Barbara Kuli, Loïc Raffray, Emilie Mosnier Pages 1039-1041 4 Reviving β-lactams for Mycobacterium abscessus: the emerging role of durlobactam β-内酰胺类抗生素重振活力治疗脓肿分枝杆菌：杜洛巴坦的新兴作用 Chengcheng Wang, Zhiyong Zong Pages 1042-1044 Editorials（社论） 5 A cutting-edge vaccine could address a gap in protection against Ebola virus disease 一种前沿疫苗有望填补埃博拉病毒病免疫保护的空白 Armand Sprecher, Sylvie Jonckheere, Michel Van Herp Pages 1045-1046 6 Widespread extended-spectrum β-lactamase–producing Enterobacterales colonization in healthy individuals in Burkina Faso: a hidden community reservoir 布基纳法索健康人群中广泛存在产超广谱β-内酰胺酶肠杆菌目细菌定植：一个隐匿的社区储库 Caroline Theunissen, Olivier Denis Pages 1047-1049 Theme Issue（主题专刊） Theme Issue Editorial（专题社论） 7 Microbiome science at a turning point: from descriptive ecology to clinical decision making in infectious diseases 微生物组学正处于转折点：从描述性生态学走向感染性疾病的临床决策 Silvia Corcione, Nicolas Benech, Ed Kuijper Pages 1050-1051 Theme Issue Reviews（专题综述） 8 Role of the gut microbiome in shaping drug response in immunocompromised hosts 肠道微生物组在免疫功能低下宿主药物应答中的作用 Semeh Bejaoui, Federica D'Amico, Silvia Turroni Pages 1052-1059 9 The role of the gut microbiome in multidrug-resistant organism colonization and infection 肠道微生物组在多重耐药菌定植与感染中的作用 Blair Merrick, Rebecca Cooper, Benjamin Davido, Simon D. Goldenberg Pages 1060-1066 10 Dynamics of the gut and lung microbiota in severe infections: from observational studies to therapeutic strategies 严重感染中肠道与肺部微生物群的动态变化：从观察性研究到治疗策略 Duveke P.E. de Gaay Fortman, Robert F.J. Kullberg, W. Joost Wiersinga, Bastiaan W. Haak Pages 1067-1074 11 Advanced computational analysis in metagenomic studies to support precision medicine 宏基因组研究中支持精准医学的高级计算分析 Gianmarco Piccinno, Francesco Asnicar Pages 1075-1080 12 How to set up and manage a microbiome research facility 如何建立和管理微生物组研究设施 Jannie G.E. Henderickx, Wiep Klaas Smits, Georg Zeller, Ed J. Kuijper Pages 1081-1086 Systematic Reviews（系统综述） 13 The impact of toll-like receptor polymorphisms on susceptibility to fungal infections: a systematic review of genetic and clinical data Toll样受体多态性对真菌感染易感性的影响：遗传与临床数据的系统综述 Martha Fabielle Pereira Staiger, Gleyce Hellen de Almeida Souza, James Venturini, Nalu Teixeira de Aguiar Peres, ... Luana Rossato Pages 1087-1095 14 Host blood biomarkers for the diagnosis of childhood tuberculosis disease: a systematic review and meta-analysis 用于儿童结核病诊断的宿主血液生物标志物：系统综述与荟萃分析 Michael Prodanuk, James W. King, Jessie Cunningham, Ian Kitai, ... Melissa Richard-Greenblatt Pages 1096-1106 Guidelines（指南） 15 Guiding principles for implementing ESCMID clinical practice guidelines 实施ESCMID临床实践指南的指导原则 Bianca Albers, Blin Nagavci, Oana Joean, Sarah Tschudin Sutter, ... Marcus Zervos Pages 1107-1114 Picture of a Microorganism（微生物图鉴） 16 A hard tick on the scalp visualized by polarized and ultraviolet dermoscopy 偏振光与紫外线皮肤镜下头皮上的硬蜱 Jia-Xu Li, Dan-Qiong Zheng, Yi-Ming Fan Pages 1115-1116 Original Articles（论著） 17 Genomic determinants of Bacillus cereus and outcomes of infection in preterm neonates: a multicentre retrospective study 蜡样芽孢杆菌的基因组决定因素及早产儿感染预后：一项多中心回顾性研究 Alicia Chevalier, Mariem Ben Khedher, Antoine Tran, Matilde Coin, ... Raymond Ruimy Pages 1117-1124 18 Faecal colonization with extended-spectrum β-lactamase–producing Escherichia coli and Klebsiella pneumoniae in rural Burkina Faso 布基纳法索农村地区产超广谱β-内酰胺酶大肠埃希菌和肺炎克雷伯菌的粪便定植 Daniel Valia, Ibrahima Karama, Brecht Ingelbeen, Zakaria Garba, ... Hector Rodriguez-Villalobos Pages 1125-1134 19 Changes in nasal and throat microbiota composition during and after mupirocin and chlorhexidine decolonization treatment in asymptomatic methicillin-resistant Staphylococcus aureus carriers: a longitudinal observational study 无症状耐甲氧西林金黄色葡萄球菌携带者接受莫匹罗星与氯己定去定植治疗期间及之后鼻咽部微生物群组成的变化：一项纵向观察研究 Sofie Marie Edslev, Cindy M. Liu, Bobby Zhao Sheng Lo, Heidi Meiniche, ... Marc Stegger Pages 1135-1143 20 Clinical utility of the DENOVA score for predicting infective endocarditis in Enterococcus faecalis bacteraemia: external validation with decision curve analysis DENOVA评分预测粪肠球菌菌血症感染性心内膜炎的临床效用：基于决策曲线分析的外部验证 Benedetta Varisco, Daniele Piovani, Elena Rosselli Del Turco, Linda Bussini, ... Martina Spaziante Pages 1144-1151 21 Clinical validation of a new multi-Aspergillus species reverse transcriptase quantitative PCR: a diagnostic case-control study 新型多曲霉属逆转录酶定量PCR的临床验证：一项诊断性病例对照研究 Marion Benazra, Wicem Mallek, Théo Ghelfenstein-Ferreira, Aude Sturny-Leclère, ... Alexandre Alanio Pages 1152-1157 22 A phase Ib, placebo-controlled randomized clinical trial of the Ebolavirus DNA vaccine candidate INO-4201 followed by electroporation as booster vaccination in healthy, rVSVΔG-ZEBOV-GP-primed volunteers (Boost-EBOV) 一项关于埃博拉病毒DNA疫苗候选物INO-4201的Ib期、安慰剂对照、随机临床试验，该试验在健康、已接种rVSVΔG-ZEBOV-GP的初免志愿者中，以电穿孔作为加强接种（Boost-EBOV） Angela Huttner, Marc-Antoine de La Vega, Cristina Boehm-Bosmani, Jean Boyer, ... Gary P. Kobinger Pages 1158-1164 23 Burden of HIV and hepatitis B and C viruses in incoming Venezuelan migrants at the Colombian border: a laboratory-based cross-sectional study, 2021–2023 2021–2023年哥伦比亚边境入境委内瑞拉移民中HIV及乙型和丙型肝炎病毒的负担：一项基于实验室的横断面研究 Felix Lehmann, Ruth Aralí Martínez-Vega, Andres Moreira-Soto, Carlos Hernán Becerra-Mojica, ... Jan Felix Drexler Pages 1165-1170 24 Association between early SARS-CoV-2 viral rebound and post-COVID conditions among immunocompromised patients: cohort study 免疫功能低下患者中早期SARS-CoV-2病毒反弹与新冠后遗症的关联：队列研究 Guozhang Lin, Yuchen Wei, Carlos King Ho Wong, Xi Xiong, ... Ka Chun Chong Pages 1171-1178 Research Note（研究简讯） 25 From compliance to complexity: the impact of in vitro diagnostic regulation for clinical microbiology laboratories 从合规到复杂：体外诊断法规对临床微生物学实验室的影响 Sangeeta Gaja-Lachman, Mariëlle De Visser-Timmermans, Diana Langerak, Amber Jansma, Erlangga Yusuf Pages 1179-1182 Letters（读者来信） 26 Emerging extraintestinal Vibrio infections in Ireland from clinical and marine sources, 2020–2022 2020–2022年爱尔兰来自临床与海洋来源的新兴肠道外弧菌感染 Brigid Hooban, Seán Olann Whelan, Amy Burke, Mary Lucey, ... Georgios Miliotis Pages 1183-1186 27 Neisseria meningitidis MenY ST-1466 harbouring Neisseria gonorrhoeae 16S rRNA allele causing false-positive Aptima® gonococcal nucleic acid amplification test results 携带淋病奈瑟菌16S rRNA等位基因的脑膜炎奈瑟菌MenY ST-1466导致Aptima®淋球菌核酸扩增检测假阳性 Sebastiaan J. van Hal, Emma Goeman, Yvette Davidson, Frances Jenkins, ... Monica Lahra Pages 1187-1189 28 Nationwide emergence of cefotaxime-resistant Neisseria meningitidis via interspecies gene transfer from penA795-bearing Neisseria commensals in China 中国境内通过种间基因转移自携带penA795的奈瑟菌属共生菌而出现的全国性头孢噻肟耐药脑膜炎奈瑟菌 Youxing Shao, Xin Lan, Mingliang Chen, Minggui Wang, Qinglan Guo Pages 1190-1192 29 Carbapenemase-producing Klebsiella pneumoniae harbouring virulence-associated genes among war-affected children from the Gaza Strip 加沙地带受战争影响儿童中携带毒力相关基因的产碳青霉烯酶肺炎克雷伯菌 Andrés Pérez-López, Anju Sharma, Ruwa Mohamed, Clement K.M. Tsui, ... Mohammed Suleiman Pages 1193-1195 Corrigendum（勘误） 30 Corrigendum to “A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study” [Clin Microbiol Infect 28 (2) (2022) 298.e9–e15] 勘误："一种高致死率且鼻咽拭子RT-PCR检测灵敏度低的新型SARS-CoV-2变异株：一项观察性研究" [Clin Microbiol Infect 28 (2) (2022) 298.e9–e15] Pierre Fillâtre, Marie-José Dufour, Sylvie Behillil, Rémi Vatan, ... Nicolas Massart Page 1196 Clinical Microbiology and Infection[Jour] AND 32[volume] AND 7S[issue] 临床微生物学与感染 32卷 7期增刊 https://www.sciencedirect.com/journal/clinical-microbiology-and-infection/vol/32/issue/7/suppl/S The role of whole genome sequencing in antimicrobial susceptibility prediction of bacteria: 2025 update from the EUCAST Subcommittee 全基因组测序在细菌抗菌药物敏感性预测中的应用 —— 欧洲抗微生物药物敏感性试验委员会分委会 2025 年更新报告 The publication of this supplement has been sponsored by the Antibiotic Resistance and Pathogenicity of Bacterial Infections Research Group, Instituto de Investigaci\xF3n Sanitaria Illes Balears (IdISBa) 本增刊出版由巴利阿里群岛卫生研究所（IdISBa）细菌感染耐药与致病性研究组资助 The role of whole genome sequencing in antimicrobial susceptibility prediction of bacteria: 2025 update from the European Committee on Antimicrobial Susceptibility Testing Subcommittee 全基因组测序在细菌抗菌药物敏感性预测中的应用 —— 欧洲抗微生物药物敏感性试验委员会分委会 2025 年更新报告 Ørjan Samuelsen, Carla López-Causapé, Frank Møller Aarestrup, Valeria Bortolaia, ... Antonio Oliver Pages S1-S34 【abstract】（摘要） Scope: The 2017 European Committee on Antimicrobial Susceptibility Testing (EUCAST) subcommittee report on the role of whole genome sequencing (WGS) in antimicrobial susceptibility testing (AST) concluded that WGS antimicrobial susceptibility prediction (WGS-ASP) was not a sufffciently robust alternative to AST to guide clinical decision making at that stage and that more evidence was required [1]. Since then, the use of WGS, bioinformatic tools, machine learning (ML)/artiffcial intelligence (AI), databases, and prediction approaches has greatly expanded, along with an increased knowledge of resistance mechanisms and their contribution to antimicrobial susceptibility. In response, a new EUCAST ad hoc subcommittee was established in 2024 to review the literature, with the aim of assessing the current potential and limitations of WGS-ASP. 研究范围：2017年欧洲抗微生物药物敏感性试验委员会（EUCAST）分委会发布的全基因组测序（WGS）用于抗菌药物敏感性试验（AST）专项报告指出，彼时全基因组测序抗菌药物敏感性预测技术（WGS-ASP）稳定性不足，尚无法替代表型药敏试验指导临床诊疗决策，仍需积累更多研究证据[1]。此后，全基因组测序技术、生物信息学分析工具、机器学习/人工智能算法、耐药数据库及基因型预测模型得到广泛应用；同时，学界对抗菌药物耐药机制及其对药敏表型的影响认知持续深化。为此，EUCAST于2024年成立专项临时分委会，系统梳理现有文献，评估当前WGS-ASP技术的应用潜力与现存局限。 Methods: As in the previous report, the subcommittee reviewed the literature on a ‘by organism’ basis but expanded the list to also include enterococci, Haemophilus inffuenzae, and Bacteroides fragilis in addition to those already included in the ffrst version: Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, Neisseria gonorrhoeae, Staphylococcus aureus, Streptococcus pneumoniae, Clostridioides difffcile, and Mycobacterium tuberculosis. Additional sections were included to cover advances in metagenomics, other omics technologies and ML/AI. The full report was compiled and reviewed by all subcommittee members before public consultation in November 2025. 研究方法：与上一版报告一致，本分委会按照菌种分类开展文献综述；相较于初版，本次扩充菌种覆盖范围，除原有肠杆菌目、铜绿假单胞菌、鲍曼不动杆菌、淋病奈瑟菌、金黄色葡萄球菌、肺炎链球菌、艰难梭菌、结核分枝杆菌外，新增肠球菌、流感嗜血杆菌、脆弱拟杆菌。报告增设独立章节，系统阐述宏基因组学、其他组学技术及机器学习/人工智能领域的研究进展。完整报告经全体分委会成员编撰、内审后，于2025年11月面向公众征求意见。 Conclusions and Recommendations: Signiffcant progress has been achieved in WGS-ASP, with growing evidence supporting its ability to distinguish wild-type from non—wild-type isolates and, consequently, susceptible from resistant strains, particularly for M. tuberculosis and when clinical breakpoints align with the epidemiological cut-off (ECOFF). Despite these advances, important challenges remain before WGS-ASP can be adopted as a clinical decision-making tool. Addressing these gaps will require integrated phenotypic and genotypic surveillance to strengthen the evidence base for complex resistance mechanisms and newer antimicrobial agents, alongside comparative assessments that consider both ECOFF and clinical breakpoints. The analyses will require reference method phenotypic AST and highquality genomic data. It is critical to ensure that datasets reffect the target populations and encompass the full spectrum of antimicrobial susceptibility, while developing uniffed interpretation frameworks and harmonized bioinformatics tools to standardize outputs. Robust external quality assessment schemes will be essential for clinical validation, and emerging technologies such as AI and ML offer promising avenues to enhance predictive accuracy. Finally, improvements in cost and turnaround time, coupled with evaluations of setting-speciffc cost-effectiveness, will be key to enabling practical implementation of WGS-ASP. 结论与建议：WGS-ASP技术已取得长足进展，现有大量证据证实该技术可区分野生型菌株与非野生型菌株，进而判别敏感株与耐药株；针对结核分枝杆菌的检测优势尤为突出，且当临床折点与流行病学临界值（ECOFF）一致时检测效果更佳。尽管技术进步显著，若要将WGS-ASP作为临床常规决策工具，仍存在诸多亟待解决的难题。需联合开展表型-基因型一体化耐药监测，完善复杂耐药机制与新型抗菌药物相关研究证据；同时同步结合流行病学临界值与临床折点开展对比验证。相关研究需配套参比标准表型药敏试验与高质量基因组测序数据。数据集需贴合目标人群特征，覆盖全部药敏表型谱系；同时搭建统一判读体系、标准化生物信息学工具，实现检测结果规范化输出。完善、可靠的室间质评体系是该技术完成临床验证的核心保障；人工智能、机器学习等新兴技术可有效提升药敏预测准确度，具备良好应用前景。最后，降低检测成本、缩短报告周转时长，并结合不同医疗场景开展卫生经济学效益评估，是推动WGS-ASP落地临床实际应用的关键。 Ørjan Samuelsen, Clin Microbiol Infect 2026;32:S3 作者：厄尔扬·萨缪尔森发表期刊：《临床微生物学与感染》2026年；32卷：增刊3 Clinical Microbiology and Infection[Jour] AND 32[volume] AND 8[issue] 临床微生物学与感染 32卷 8期 https://www.sciencedirect.com/journal/clinical-microbiology-and-infection/vol/32/issue/8 Commentaries（述评） 1 Andes hantavirus outbreak on a cruise ship—an European Society of Clinical Microbiology and Infectious Disease Emerging Infections Subcommittee rapid assessment 邮轮安第斯汉坦病毒暴发——欧洲临床微生物与感染病学会新发感染分委会快速评估 Marta Mora-Rillo, Nitin Gupta, Effrossyni Gkrania-Klotsas, Jan Felix Drexler, ... Martin P. Grobusch Pages 1197-1201 2 Bundibugyo Ebolavirus outbreak in the Democratic Republic of the Congo and Uganda: rapid assessment from the European Society of Clinical Microbiology and Infectious Diseases Emerging Infections Subcommittee 刚果民主共和国与乌干达本迪布焦埃博拉病毒暴发：欧洲临床微生物与感染病学会新发感染分委会快速评估 Nitin Gupta, Marta Mora-Rillo, Effrossyni Gkrania-Klotsas, Jan Felix Drexler, ... Sotirios Tsiodras Pages 1202-1207 3 Beyond sensitivity and specificity: designing outcome-driven evidence for infectious disease in vitro diagnostics 超越灵敏度与特异度：构建以临床结局为导向的感染病体外诊断循证依据 Benjamin Hommel Pages 1208-1210 4 Rethinking informed consent in phage therapy: why location and approach matter 重新审视噬菌体疗法知情同意：实施场景与沟通方式的关键价值 Ran Nir-Paz, Jean-Paul Pirnay, Tristan Ferry, Zuzanna Drulis-Kawa, ... Gina A. Suh Pages 1211-1215 5 Which trial do we need? The Selective Digestive Decontamination Herd Effects Estimation Trial (SHEET) study 我们需要何种临床试验？选择性消化道去污群体效应评估（SHEET）研究 James C. Hurley Pages 1216-1220 Editorial（社论） 6 Inputs of robust observational studies on encephalitis: the game will never be over 高质量观察性研究对脑炎诊疗的价值：探索永无止境 Pierre Fillâtre, Alexandra Mailles, Jean-Paul Stahl, Sylviane Defres, Pierre Tattevin Pages 1221-1223 Theme Issue（专刊） Theme Issue Editorial（专刊社论） 7 On silence and modesty 论医学研究中的审慎与谦逊 Katharina Last Page 1224 Theme Issue Reviews（专题综述） 8 Hybrid effectiveness-implementation studies in infection prevention and infectious diseases: a narrative review 感染防控领域效果-实施混合研究：叙述性综述 Lauren Clack, Marie-Therese Schultes, Bianca Albers, Aline Wolfensberger Pages 1225-1237 9 Anthropology of infectious disease emergence and epidemic control: a review 新发传染病与疫情防控的人类学视角：综述 Tamara Giles-Vernick, Jules Villa Pages 1238-1243 10 The human cost of resistance: ethical implications of coping with isolation for multidrug resistant organisms 耐药带来的人文代价：多重耐药菌隔离管理的伦理考量 Sibylle C. Mellinghoff, Alessandra A. Grossi, Claudia Recanatini, Leonie Breull-Wierschem, ... Norma Jung Pages 1244-1249 Narrative Reviews（叙述性综述） 11 Blood vessels at the crossroads: angiogenesis in the intersection of HIV and atherosclerosis 血管的交叉病理：HIV合并动脉粥样硬化中的血管新生机制 Pere Domingo, Paula Prieto, Marta Giralt, Didac Mauricio, Elvira Fernández Pages 1250-1259 12 Antifungal susceptibility testing across fungi: why MICs vary and methods diverge and what MIC can miss 广谱真菌药敏检测：最低抑菌浓度差异、检测方法分歧及检测盲区 Cornelia Lass-Flörl, Maximilian Lass, Jan Marco Kern, Silke Huber Pages 1260-1264 13 Antimicrobial stewardship during extracorporeal membrane oxygenation: challenges and new perspectives 体外膜肺氧合（ECMO）期间抗菌药物精细化管理：挑战与新进展 Salman Abdulaziz, Hanan Salah Alhajri, Miranda So, Salman Butt, ... Daniel Brodie Pages 1265-1272 Systematic Reviews（系统综述） 14 Nudging in MicroBiology laboratory Evaluation (NiMBLE): a systematic review and meta-analysis 微生物实验室干预引导策略（NiMBLE）：系统综述与荟萃分析 Bradley J. Langford, Elizabeth Leung, Esther Jeong, Kevin A. Brown, ... Larissa M. Matukas Pages 1273-1285 Position Paper（立场声明） 15 Language, trust, and the polio endgame: words matter in vaccine communication 语言、公众信任与脊髓灰质炎消除攻坚：疫苗科普沟通的措辞策略 Sotirios Tsiodras, Nitin Gupta, Thomas Hanscheid, Pikka Jokelainen, ... Martin P. Grobusch Pages 1286-1292 Picture of a Microorganism（微生物图鉴） 16 Plectosphaerella cucumerina fungal keratitis in an uncommon presentation 黄瓜隔孢菌所致非典型真菌性角膜炎 Lipeng Wang, Lihua Jiang, Shujun Liu, Maoli Yi Pages 1293-1294 Original Articles（论著） 17 Performance of an antigen test for detection of SARS-CoV-2, influenza, and respiratory syncytial virus—a prospective study 新冠病毒、流感病毒、呼吸道合胞病毒三联抗原检测效能：前瞻性研究 Karoline Berger, Siv-Hege Vang, Roy H.O. Bekkeseth, Anders Bredberg Pages 1295-1301 18 Risk of major structural birth defects following repeat mRNA COVID-19 vaccination in the first trimester: a population-based cohort study 孕早期重复接种mRNA新冠疫苗后重大结构性出生缺陷风险：基于人群的队列研究 Liang En Wee, Muhammad Ismail Bin Abdul Malek, Reen WL Ho, Jue Tao Lim, ... Kelvin B. Tan Pages 1302-1310 19 Persistence of late HIV diagnosis and poorer response to antiretrovirals: a comparison between migrants and native-born people with HIV in Spain HIV晚诊持续现状及抗逆转录病毒治疗应答不佳：西班牙移民与本土HIV感染者对比研究 Jose A. Perez-Molina, Miguel Suárez-Robles, María Belén Sánchez-López, Francisco Tejerina, ... M Ángeles Muñoz-Fernández Pages 1311-1321 20 Emergence of novel zoonotic and multidrug-resistant Streptococcus suis lineages 新型人兽共患病多重耐药猪链球菌谱系的出现 Jaime Brizuela, Gemma G.R. Murray, Parichart Boueroy, Andrew J. Balmer, ... Constance Schultsz Pages 1322-1330 21 Pharmacokinetic and pharmacodynamic evaluations of oral moxifloxacin for Enterococcus faecalis endocarditis 口服莫西沙星治疗粪肠球菌心内膜炎的药代动力学/药效学评价 Magnus Bock, Johan G.C. Van Hasselt, Kurt Fuursted, Nikolaj Ihlemann, ... Claus Moser Pages 1331-1337 22 Infectious encephalitis among adults: a prospective and population-based cohort study 成人感染性脑炎：前瞻性人群队列研究 Lærke Storgaard Duerlund, Lykke Larsen, Merete Storgaard, Helene Mens, ... Jacob Bodilsen Pages 1338-1346 23 Doxycycline in the treatment of outpatient mild community-acquired pneumonia: a propensity-matched retrospective cohort study 多西环素治疗门诊轻型社区获得性肺炎：倾向得分匹配回顾性队列研究 Genady Drozdinsky, Asaf Ness, Melanie Shahar, Shiri Kushnir, ... Noa Eliakim-Raz Pages 1347-1351 24 Rifapentine dosing for drug-susceptible tuberculosis: stage 1 of a seamless phase 2/3 randomized clinical trial 利福喷丁治疗药物敏感肺结核给药方案：无缝Ⅱ/Ⅲ期随机临床试验第一阶段研究 Yang Li, Lingyun Song, Zhen Feng, Xiaoqiang Zhang, ... Wenhong Zhang Pages 1352-1359 Research Notes（研究简报） 25 First reported case of Andes hantavirus cardiopulmonary syndrome treated with a combination of favipiravir, ribavirin, icatibant and baricitinib 法匹拉韦、利巴韦林、艾替班特联合巴瑞替尼救治安第斯汉坦病毒心肺综合征首例报道 Miriam Estébanez, María Simón Sacristán, Tatiana Mata Forte, Anabel Negredo, ... Francisco Javier Areta Jimenez Pages 1360-1366 Letters（读者来信） 26 Re: ‘ESCMID clinical guidelines on the evaluation and management of a reported antibiotic allergy’ by Joean et al. 回应：Joean等人《ESCMID抗生素过敏评估与临床治疗指南》 Ignacio Martin-Loeches, Sean Keane Pages 1367-1368 27 ‘ESCMID clinical guidelines on the evaluation and management of a reported antibiotic allergy’—author’s reply 《ESCMID抗生素过敏评估与临床治疗指南》——作者回复 Oana Joean, Kevin Sermet, Blin Nagavci, Jonathan Sandoe, Mark de Boer Pages 1369-1370 28 Antibiotic allergy delabeling requires more than guidelines: the role of patient perspective 抗生素过敏去标签管理不能仅依靠指南：患者主观视角的重要作用 Neda Milevska-Kostova, Teske Schoffelen, Tessa Langeveld, Jeroen Schouten, Marlies E.J.L. Hulscher Pages 1371-1372 29 Re: ‘Clinical utility of the DENOVA score for predicting infective endocarditis in Enterococcus faecalis bacteraemia: external validation with decision curve analysis’ by Varisco et al. 回应：Varisco等人《DENOVA评分预测粪肠球菌菌血症并发感染性心内膜炎的临床价值：决策曲线分析外部验证》 Pierre Danneels, Floris Chabrun, Baptiste Clément, Xavier Duval, Vincent Dubée Pages 1373-1374 30 Clinical utility of the DENOVA score for predicting infective endocarditis in Enterococcus faecalis bacteraemia—Author's reply DENOVA评分预测粪肠球菌菌血症并发感染性心内膜炎的临床价值——作者回复 Benedetta Varisco, Linda Bussini, Davide Fiore Bavaro, Michele Bartoletti Pages 1375-1376 Clinical Microbiology and Infection[Jour] AND 32[volume] AND 9[issue] 临床微生物学与感染 32卷 9期 https://www.sciencedirect.com/journal/clinical-microbiology-and-infection/vol/32/issue/9 Commentaries（述评） 1 Advancing medicine, undermining life: a global health contradiction 推动医学进步却损害生命：一项全球卫生领域的矛盾 Edmond Puca, Francesca Rossi, Rima Moghnieh, Lukas Tometten, ... Ricardo Strauss Pages 1377‑1379 2 A European perspective on antibiotic use in viral respiratory infections: new paradigm integrating pathogens with host factors 病毒性呼吸道感染抗生素应用的欧洲观点：整合病原体与宿主因素的新模式 Şiran Keske, Virginie Prendki, Paraskevi C. Fragkou, Jordi Rello, the ESGREV and ESGIE Pages 1380‑1383 3 Antibiotic prophylaxis: a sharp tool that could be blunted easily 抗生素预防：一把易被钝化的利器 Marek Stefan, Marcela Krutova Pages 1384‑1387 3 Beyond the ward: the evolving roles of infectious disease specialists 走出病房：感染病专科医师角色的演变 Konstantinos Alexakis, Angela Ishak, Nikolaos Mazonakis, Constantinos Tsioutis, Nikolaos Spernovasilis Pages 1388‑1392 Editorial（社论） 4 From surveillance to participation: redefining respiratory virus epidemiology in the era of self‑testing 从监测到参与：自检时代下呼吸道病毒流行病学的重新定义 Markus Fally, Alexander G. Mathioudakis Pages 1393‑1395 5 Time to tap early: do not delay lumbar puncture in older adults 宜尽早实施：老年患者不应延迟腰椎穿刺 Marion Le Maréchal, Mathieu Vaillant Pages 1396‑1397 6 Can we improve on standard cefoxitin dosing for surgical prophylaxis? 外科预防用药中，我们能否优化头孢西丁标准给药方案？ Sheryl A. Zelenitsky Pages 1398‑1400 7 Diagnosing and managing unexpected donor bloodstream infection in organ transplantation 器官移植中供体不明原因血流感染的诊断与处理 Maddalena Giannella, Matteo Rinaldi Pages 1401‑1403 Narrative Reviews（叙述性综述） 8 Nipah virus in South Asia: from emergence to enduring preparedness' challenges 南亚尼帕病毒：从病毒出现到持续防控准备面临的挑战 Nitin Gupta, Effrossyni Gkrania‑Klotsas, Jan Felix Drexler, Sayantan Banerjee, ... Sotirios Tsiodras Pages 1404‑1411 9 Emerging mycoses: a neglected area of concern for global health 新发真菌病：全球卫生被忽视的关注点 Aleksandra Barac, Oliver A. Cornely, José Ramón Paño‑Pardo, Nitin Gupta, ... Martin P. Grobusch Pages 1412‑1417 10 New antifungals for the treatment of invasive mould disease 用于侵袭性霉菌病治疗的新型抗真菌药物 Nancy N. Vuong, David R. McClung, Samuel L. Aitken, Caitlin R. Rausch Pages 1418‑1424 11 Questions and issues of nonventilated hospital‑acquired pneumonia: an opinion document 非机械通气医院获得性肺炎的若干问题：一份专家意见文件 Marina Fayos, Almudena Burillo, Alicia Galar, Ana Álvarez Uría, ... Emilio Bouza Pages 1425‑1434 Systematic Reviews（系统综述） 12 Andes virus–associated cardiopulmonary syndrome: diagnostic approaches, clinical management, and evidence gaps—a scoping review 安第斯病毒相关心肺综合征：诊断手段、临床处置与证据缺口——范围综述 Federico Fama, Francesco Molà, Alberto Rizzo, Lucia Galli, ... Marta Colaneri Pages 1435‑1447 Position Paper（立场文件） 13 Position statement: integrating planetary health into infection prevention and control in healthcare settings—towards a balanced and evidence‑based approach 立场声明：将地球健康理念融入医疗机构感染预防与控制——构建均衡的循证实践路径 Ermira Tartari, Emine Alp Meşe, Andre N.H. Bulabula, Stephanie J. Dancer, ... Walter Zingg Pages 1448‑1462 Picture of a Microorganism（微生物图鉴） 14 Lumbar‑sacral giant sparganosis presenting as an intradural mass 表现为硬脊膜内占位的腰骶部巨大裂头蚴病 Jiarui Chen, Xinli Zhan, Chengqian Huang, Mingbo Wang, ... Chong Liu Pages 1463‑1464 Original Articles（原创论著） 15 Performance of a rapid, visual fingerstick serology self‑test for Helicobacter pylori detection and typing: a prospective multicentre diagnostic accuracy study 幽门螺杆菌检测及分型的指尖采血可视化血清学快速自检试剂盒效能：一项前瞻性多中心诊断准确性研究 Jing Chen, Tingting Wang, Song Liu, Jing Xiang, ... Changjiang Hu Pages 1465‑1471 16 Diagnostic accuracy and potential resource savings of pooled sputum testing with Xpert MTB/RIF Ultra for tuberculosis among adults in Vietnam: a cross‑sectional study 越南成人肺结核采用Xpert MTB/RIF Ultra混合痰液检测的诊断效能与潜在医疗资源节约：一项横断面研究 Han Thi Nguyen, Andrew James Codlin, Luan Nguyen Quang Vo, Nga Thi Thuy Nguyen, ... Tom Wingfield Pages 1472‑1479 17 Self‑testing for five respiratory viruses in adults ≥50 years of age in Germany for longitudinal monitoring of community‑acquired acute respiratory infections 德国≥50岁成人5种呼吸道病毒自检用于社区获得性急性呼吸道感染的纵向监测 Julia A. Nacov, Jon Salmanton‑García, Julia Jakobs, Miranda Anggitakirana, ... Oliver A. Cornely Pages 1480‑1486 18 Blinded two‑year longitudinal evaluation of SARS‑CoV‑2 antigenemia in long COVID 长新冠患者新冠病毒抗原血症为期两年的盲法纵向评估 Lourdes Mateu, Louise L. Hansen, Joao Pedro Carmezim, Cora Loste, ... Marta Massanella Pages 1487‑1494 19 Early vs late diagnosis in infectious encephalitis: a population‑based cohort study 感染性脑炎早期与晚期诊断对比：一项基于人群的队列研究 Lærke Storgaard Duerlund, Lykke Larsen, Merete Storgaard, Helene Mens, ... Jacob Bodilsen Pages 1495‑1502 20 Target‑controlled infusion vs. standard dosing of cefoxitin for surgical prophylaxis in colorectal surgery: a randomized clinical trial 结直肠外科手术预防感染：头孢西丁靶控输注与标准给药方案对比的随机临床试验 Jong Lyul Lee, Ha‑Jung Kim, Kyung Mi Kim, Jung‑Min Yi, ... In Ja Park Pages 1503‑1509 21 Impact of generic market entry on the consumption of last‑resort antibiotics in six European countries 仿制药上市对6个欧洲国家终极抗生素使用量的影响 Caroline Schweizer, Sebastian Weis, Evelina Tacconelli, Stephan Harbarth, ... Miriam Kesselmeier Pages 1510‑1516 22 Association between unrecognized donor bloodstream infection and outcomes in solid organ transplant recipients: a prospective observational cohort study 未被发现的供体血流感染与实体器官移植受者预后的关联：一项前瞻性观察队列研究 Andrea Cona, Caterina Curatolo, Paola Giordani, Flavia D'Andrea, ... Alessandra Mularoni Pages 1517‑1525 Research Note（研究简报） 23 Multicentre validation of EUCAST disk diffusion for frequently encountered anaerobic bacteria (excluding Cutibacterium acnes) in clinical microbiology laboratories in the Netherlands 荷兰临床微生物实验室针对常见厌氧菌（痤疮棒状杆菌除外）EUCAST纸片扩散法的多中心验证 Erlangga Yusuf, Wouter van den Bijlaardt, Helke van Dessel, Thomas Dierikx, ... Alida CM. Veloo Pages 1526‑1530 24 Ceftazidime‑avibactam‑resistant Klebsiella pneumoniae driven by multiple β‑lactamase mutations: a hospital outbreak report 多种β‑内酰胺酶突变介导的耐头孢他啶‑阿维巴坦肺炎克雷伯菌：一起医院暴发报告 Weiwei Yang, Chengkang Tang, Qingyu Shi, Hongjian Ou, ... Fupin Hu Pages 1531‑1535 Letters（读者来信） 25 Re: ‘Meropenem and fosfomycin against Klebsiella pneumoniae’ by Wicha et al. 对Wicha等人《美罗培南联合磷霉素抗肺炎克雷伯菌》一文的回复 Guofu Mao, Haizhen Lan Pages 1536‑1537 26 Meropenem and fosfomycin against Klebsiella pneumoniae: author‘s response 《美罗培南联合磷霉素抗肺炎克雷伯菌》：作者回复 Aneeq Farooq, Miklas Martens, Marie L.G. Attwood, Patrice Nordmann, ... Sebastian G. Wicha Pages 1538‑1539 27 Re: ‘Invasive fungal infections after CD19 chimeric antigen receptor‑T‑cell therapy for B‑cell lymphoma: a lymphoma study association study from the DESCAR‑T registry’ by Bouvier et al. 对Bouvier等人《B细胞淋巴瘤CD19嵌合抗原受体T细胞治疗后侵袭性真菌感染：DESCAR‑T登记库淋巴瘤研究联盟研究》一文的回复 Jice Wang Pages 1540‑1541 28 Invasive fungal infections after cluster of differentiation (CD19) chimeric antigen receptor (CAR) T‑cell therapy for B‑cell lymphoma: author’s response B细胞淋巴瘤CD19嵌合抗原受体T细胞治疗后侵袭性真菌感染：作者回复 Amélie Bouvier, François Lemonnier, Giovanna Melica Pages 1542‑1543 29 Tackling clinical research fragmentation in public health emergencies in Europe 应对欧洲突发公共卫生事件下临床研究碎片化问题 Evelyn Depoortere, Corinna Hartung, Teresa Chavarria Gimenez, Patricia Urbán, Cornelius Schmaltz Pages 1544‑1545 30 Delayed intestinal adenovirus response to intravenous brincidofovir in paediatric allogeneic stem cell transplant recipients displaying rapid clearance of the virus from peripheral blood 儿童异基因干细胞移植受者外周血腺病毒快速清除，但肠道腺病毒对静脉布林西多福韦应答延迟 Chantal Lucini, Sandra Preuner, Lisa Grösslinger, Nkechi Azie, Thomas Lion Pages 1546‑1548 Clinical Microbiology and Infection[Jour] AND 32[volume] AND 10[issue] 临床微生物学与感染 32卷 10期 https://www.sciencedirect.com/journal/clinical-microbiology-and-infection/vol/32/issue/10 Editorial Note（编者按） 1 Clinical Microbiology and Infection: how did we do in 2025? 《临床微生物学与感染》：2025年发展回顾 J. Friedman Pages 1549-1551 Commentary（述评） 2 Andes virus at rural–urban interfaces: avoiding alarm while broadening One Health surveillance 城乡交界地带的安第斯病毒：在避免恐慌的同时拓展"同一健康"监测 Giancarlo Ceccarelli, Francesco Branda, Fabio Scarpa, Massimo Ciccozzi Pages 1552-1555 3 Which randomized controlled trial do we need? Routine replacement versus clinically indicated replacement for peripheral venous catheters for reducing bloodstream infections: a cluster-randomized controlled trial 我们需要怎样的随机对照试验？外周静脉导管常规更换与临床指征更换降低血流感染的比较：一项整群随机对照试验 Lauro Damonti, Holly Jackson, Davide Bosetti, Domenica Flury, ... Niccolò Buetti Pages 1556-1559 Standing on the Shoulders of Giants（薪火相传） 4 Three decades shaping infection prevention and control: a narrative review on Petra Gastmeier's achievements 三十年塑造感染防控：Petra Gastmeier学术成就叙述性综述 Luisa A. Denkel, Friederike Maechler, Seven Aghdassi, Michael Behnke, ... Christine Geffers Pages 1560-1574 Editorial（社论） 5 Antimicrobial resistance should be a core outcome in antimicrobial randomized controlled trials 抗菌药物耐药性应作为抗菌药物随机对照试验的核心结局指标 Adam S. Komorowski Pages 1575-1577 6 Towards precision piperacillin dosing in the critically ill 迈向危重患者哌拉西林精准给药 Dirk Jan A.R. Moes, Martine G. Caris, Anne-Grete Märtson, Mark G.J. de Boer, Johan G.C. van Hasselt Pages 1578-1580 7 Antifungal prophylaxis in influenza-associated pulmonary aspergillosis: addressing persistent challenges 流感相关肺曲霉病的抗真菌预防：应对持续存在的挑战 Olivier Paccoud, Simon Feys, Sarah Dellière Pages 1581-1583 8 Lessons from the past: what a national e-prescribing protocol tells us about the limits of restrictive approaches to antimicrobial stewardship 历史的教训：国家电子处方方案揭示的抗菌药物管理限制性策略的局限性 Hidenobu Matsuzaki, Yusuke Hidaka, Shinya Tsuzuki Pages 1584-1586 Narrative Reviews（叙述性综述） 9 Hantavirus risk and preparedness in Europe in an era of climate change and global mobility 气候变化与全球流动时代下欧洲汉坦病毒风险与应对准备 Maciej Grzybek, Tarja Sironen, Heikki Henttonen, Åke Lundkvist, ... Ravi Kant Pages 1587-1594 10 Methods for determining indications for antibiotic prescriptions to facilitate antimicrobial stewardship: a scoping review 用于明确抗生素处方指征以促进抗菌药物管理的方法：范围综述 Suzanne M.E. Kuijpers, Martijn Siepel, Martijn C. Schut, Reinier van Hest, ... Jan M. Prins Pages 1595-1602 11 Potential biases in observational infectious disease studies: examples using directed acyclic graphs 观察性传染病研究中的潜在偏倚：有向无环图示例 Erlangga Yusuf, Oksana Martinuka, Frits R. Rosendaal Pages 1603-1610 Systematic Reviews（系统综述） 12 Shorter- vs. longer-course antibiotics in children with acute uncomplicated UTIs: a systematic review and meta-analyses 儿童急性单纯性尿路感染短疗程与长疗程抗生素比较：系统综述与Meta分析 Ming Liu, Qi Wang, PeiJing Yan, ZhiFan Li, ... Ya Gao Pages 1611-1619 13 Reporting of antibiotic resistance in randomized controlled trials of new antibiotics: a systematic review 新型抗生素随机对照试验中抗生素耐药性的报告情况：系统综述 Itay Zahavi, Amir Tafesh, Nimrod Puri, Asha K. Rajan, ... Mical Paul Pages 1620-1634 Guidelines（指南） 14 The ESCMID framework for reaching consensus in clinical guidelines 欧洲临床微生物学与感染病学会（ESCMID）临床指南共识制定框架 Blin Nagavci, Oana Joean, Sarah Tschudin-Sutter, Evelina Tacconelli, ... Luigia Scudeller Pages 1635-1642 Picture of a Microorganism（微生物图鉴） 15 An unwanted souvenir from Southern Europe: visceral leishmaniasis 来自南欧的"不想要的纪念品"：内脏利什曼病 An-Sofie Wellens, Lynn Rutsaert, Maarten Van Hemelen Pages 1643-1644 Original Article（论著） 16 Real-world influenza surveillance and vaccine effectiveness in children: a multicentre study of the Italian Federation of Primary Care Paediatricians 儿童流感现实监测与疫苗有效性：意大利基层保健儿科医师联合会多中心研究 Martino Barretta, Silvia Ricci, Adele Compagnone, Rosaria Indaco, ... Silvana Brenna Pages 1645-1653 17 Pharmacokinetics, target attainment, and outcomes of piperacillin/tazobactam in critically ill patients receiving continuous infusion with therapeutic drug monitoring: a retrospective analysis 哌拉西林/他唑巴坦持续输注联合治疗药物监测在危重患者中的药代动力学、目标达成与临床结局：回顾性分析 Ute Chiriac, Max Münchow, Anka C. Röhr, Otto R. Frey, ... Alexander Brinkmann Pages 1654-1661 18 Early antifungal prophylaxis fails to prevent influenza-associated pulmonary aspergillosis in the ICU: a target trial emulation 早期抗真菌预防未能预防ICU内流感相关肺曲霉病：目标试验模拟 Peng Li, Shengnan Xu, Chao Chen, Xingang Hu, ... Mingjie Sun Pages 1662-1670 19 Bidirectional associations between bacteraemia and cytomegalovirus infection after allogeneic haematopoietic cell transplantation: Japanese Society for Transplantation and Cellular Therapy Transplant Complications Working Group 异基因造血细胞移植后菌血症与巨细胞病毒感染的双向关联：日本移植与细胞治疗学会移植并发症工作组 Shun-ichi Kimura, Kazuki Yoshimura, Hideki Nakasone, Hiroki Hosoi, ... Kimikazu Yakushijin Pages 1671-1677 20 Syphilis and the risk of stroke: a nationwide, population-based matched cohort study 梅毒与卒中风险：一项全国性、基于人群的匹配队列研究 Laura Glismann, Emilie With Hall Petersen, Simone Høstgaard, Steen Hoffmann, ... Lars Haukali Omland Pages 1678-1683 21 Association between β-lactam exposure and clearance of bacteraemia and acute kidney injury in patients with methicillin-resistant Staphylococcus aureus bloodstream infections—a post hoc analysis of the CAMERA2 trial β内酰胺类药物暴露与耐甲氧西林金黄色葡萄球菌血流感染患者菌血症清除及急性肾损伤的关联——CAMERA2试验事后分析 Neta Petersiel, Amy Legg, Sean W.X. Ong, Aaron Ovadia, ... Steven Y.C. Tong Pages 1684-1692 22 Determinants of cure and survival in vascular graft and endograft infections: a 13-year single-centre cohort study 血管移植物与腔内移植物感染治愈及生存的决定因素：一项单中心13年队列研究 Dolores Sousa-Regueiro, Alicia Alonso-Alvarez, Vanesa Balboa-Barreiro, Jorge Fernández-Noya, ... Enrique Míguez-Rey Pages 1693-1700 23 Impact of E-prescribing protocols on antimicrobial prescribing for common infections in Greece: an interrupted time series analysis 电子处方方案对希腊常见感染抗菌药物处方的影响：间断时间序列分析 Elpida Mastrogianni, Sotirios Roussos, Vana Sypsa, Panagiota Mitrou, ... Michael Samarkos Pages 1701-1708 Research Note（研究简讯） 24 Isolation of hospitalized patients with influenza and COVID-19 is disproportionate to measurable contagiousness 住院流感与新冠患者的隔离措施与实际传染性不成比例 Line L. Bang, Rune M. Pedersen, Silje V. Hoegh, Thomas E. Andersen, Lone W. Madsen Pages 1709-1713 25 Characterizing the timing and causes of death in community-acquired pneumonia 社区获得性肺炎死亡时间与死因特征分析 Fatimah Al-Zergani, Alessandra Meddis, Clara Lundetoft Clausen, Pernille Ravn, ... Thomas Benfield Pages 1714-1718 Letters（读者） 26 First autochthonous mpox virus clade Ib outbreak in Italy linked to sexual transmission 意大利首次本地传播猴痘病毒Ib分支暴发与性传播相关 Valentina Mazzotta, Andrea Bongiovanni, Licia Bordi, Marco Ridolfi, ... Francesco Vairo Pages 1719-1722 27 Antibiotic resistance signature from war zones: MDRO colonization in paediatric refugees from Gaza and Ukraine compared with an Italian cohort 战区抗生素耐药特征：加沙与乌克兰难民儿童多重耐药菌定植与意大利队列比较 Elio Castagnola, Roberto Bandettini, Giuseppe Spiga, Andrea Moscatelli, ... Raffaele Spiazzi Pages 1723-1725 28 Lineages and adapted phenotypes of Pseudomonas aeruginosa persist during elexacaftor/tezacaftor/ivacaftor therapy 艾考夫托/特扎夫托/伊瓦卡夫托治疗期间铜绿假单胞菌谱系与适应表型持续存在 Maria Pals Bendixen, Oihane Irazoki, Rasmus L. Marvig, Marianne Skov, ... Helle Krogh Johansen Pages 1726-1729 29 Funguria with severe complications in diabetic patients receiving SGLT2 inhibitors 服用SGLT2抑制剂的糖尿病患者出现伴严重并发症的真菌尿 Jochem B. Buil, Rosalie B.T.M. Sterenborg, Paul E. Verweij, Puck Oude Elferink, ... Roger J. Brüggemann Pages 1730-1732 30 Comparing large language models for antibiotic prescribing: an updated analysis using the same clinical benchmark 用于抗生素处方的大语言模型比较：采用相同临床基准的更新分析 Antonio Russo, Nicholas Geremia, Davide Fiore Bavaro, Susan K. Seo, ... Andrea De Vito Pages 1733-1735 Corrigendum（勘误） 31 Corrigendum to 'Efficacy of susceptibility-matched antibiotic treatment of nontyphoidal Salmonella bloodstream infections: a prospective observational study in hospitalized children under 5 in the Democratic of Congo.' Clin Microbiol Infect. 32 (2026) 593-602 《药敏匹配抗生素治疗非伤寒沙门菌血流感染的疗效：刚果民主共和国5岁以下住院儿童前瞻性观察研究》勘误（Clin Microbiol Infect. 2026;32:593-602） Bieke Tack, Daniel Vita, Jules Mbuyamba, JoséNketo, ... Octavie Lunguya Page 1736

微生物疗法疫苗临床研究

2026-10-01

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686个靶点撑起1702个药！Nature子刊25年药物靶点全景扫描，下一个“黄金靶点”在哪？

—— 解读 Nature Reviews Drug Discovery 重磅综述《The evolving landscape of drug targets》2000年6月，人类基因组工作草图发布。彼时很多人断言：新药研发的黄金时代要来了。25年过去了，预言兑现了多少？最近，Nature Reviews Drug Discovery 刊出重磅综述《The evolving landscape of drug targets》，Halip、Avram、Overington、Oprea 等多国学者联合，基于 DrugCentral 数据库，系统盘点了截至2025年6月 FDA、EMA、PMDA 三大监管机构批准的全部药物及其作用靶点，画出了一张25年药物靶点"全家福"。今天，用一篇文章 + 文献全部图片，带你把这张图彻底看懂。一、先看总账：686个靶点，撑起1702个药先说核心数字（截至2025年6月）：全球获批药物共 1702 个，作用靶点共 686 个生物大分子。其中小分子占 79%，生物药占 19%，放射配体、无机盐等其他类型占 2%。686 个靶点里，人源蛋白占 90%（610 个），剩下 10%（76 个）来自病毒、细菌、真菌和寄生虫。这组数字怎么来的？作者的统计口径很讲究，三条规则值得注意：① 只认"直接作用靶点"。像凡德他尼，过去被标注 25 个 MoA 激酶，现在只保留 3 个真正介导疗效的；② 大蛋白复合物合并计数。线粒体复合物 I（50 个亚基）、电压门控钾通道（40 个亚基）等 7 个超过 5 亚基的复合物都按 1 个靶点算，避免靶点数量"虚胖"；③ 病原体靶点按物种去重。比如 β-内酰胺酶抑制剂阿维巴坦，不再枚举 1300 多个菌株特异条目。按同样口径回算 2017 年那版经典分析，是 544 个靶点（483 人源 + 61 病原体）——对比今天，靶点版图仍在明显扩张。【图1解读】Fig. 1 当前药物靶点格局。a：610 个人源靶点按 IUPHAR 分类——酶最多（209 个，34%），其后是 GPCR（101，17%）、离子通道（92，15%）、催化受体（73，12%）；转运体 23 个（4%）、核激素受体 19 个（3%）；"其他蛋白"51 个、内源肽 42 个。右上小图：76 个非人源靶点中细菌（32，41%）与病毒（27，35%）占大头，寄生虫 13 个、真菌 6 个。b：不同药物类型的"靶点口味"差异明显——小分子最爱酶（191 个，37%），98% 的离子通道靶点由小分子调节；GPCR 靶点数仅 74，却被 358 个小分子药物调节，是历史上"最畅销"的靶点类；核受体（19/19）与转运体（21/23）几乎被小分子垄断。生物药则偏爱催化受体（49 个，25%）与"其他靶点"（47 个），尤其擅长拦截内源肽——43 个内源肽靶点中 40 个已被 64 个生物药覆盖；其他药物类型（放射配体、无机盐等）共作用 36 个蛋白，过半是酶和 GPCR。二、2000年前后：靶点版图大洗牌作者把 2000 年（人类基因组草图发布）作为分水岭。2000 年以来，新药共引入 312 个新 MoA 靶点，比 2000 年前的 375 个增长 84%。几组对比非常刺眼：· 内源肽靶点暴涨 7.2 倍——背后是抗体药物的崛起（贝伐珠单抗拦截 VEGF-A 就是典型打法）；· 催化受体靶点翻倍——肿瘤激酶战场功不可没；· 离子通道 83→91、核激素受体 18→19，25 年几乎原地踏步；· GPCR 从"历史上最成功靶点类"（2000 年前近 29% 的药物打它）滑落到新靶点占比仅约 13%，可成药成员接近饱和。另一个标志性变化：2000 年前，靶点被小分子与生物药调节的比例是 6:1；2000 年后骤降到 1.35:1，两者平分秋色。小分子与生物药共享的靶点也从 14 个涨到 24 个。生物药也有"够不着"的地方：核受体——0 个生物药（蛋白躲在胞浆/胞核里）；离子通道 25 年只批了 1 个生物药（2004 年镇痛肽 ziconotide）；转运体也只有 1 个（2020 年抗丁肝的 bulevirtide）。而 2000 年后获批的 57 个生物药在打内源肽——小分子这边只有 voxelotor 一个孤例（结合血红蛋白 α 治疗镰刀型贫血）。【图2解读】Fig. 2 药物类型、靶点与效价的跨时期分布。a：2000 年前（左）与 2000 年后（右）引入的靶点家族对比，柱形为药物数（红=小分子、蓝=生物药），黑圈数字为 MoA 靶点数，百分比为该家族占同期新靶点的比例。2000 年前酶和离子通道为主（GPCR 60 个靶点对应 300 个药）；2000 年后酶仍居首（97 个新靶点，31.9%），催化受体（49）、其他蛋白（66）和内源肽（36，其中 35 个由生物药贡献）显著崛起。b：小分子效价箱线图——985 个药物、415 个靶点、1625 对药物-靶点相互作用，总平均效价 7.7（-log10[M]，约 50 nM）；2000 年后批准药物平均效价 8.2，显著高于 2000 年前的 7.4（Brunner–Munzel 检验 p<0.05，酶、其他蛋白、催化受体、GPCR、转运体等各组均显著），激酶抑制剂平均高达 8.4。一句话：现代药物不只是变多，还变得更精准、更"锋利"。三、25年批准曲线：一路爬坡2000–2024 年，FDA+EMA+PMDA 共批准 1091 个药，其中 826 个（76%）作用机制（MoA）明确。年均批准数从 2000–2004 年的 40 个涨到 2020–2024 年的 59 个；2020 年（73 个）和 2021 年（62 个）是历史峰值——新冠红利；2003、2005、2010 年则是低谷（不足 30 个）。有意思的是，"有明确 MoA 靶点"的药物占比 25 年间稳定在 76%（s.d.=7.6%）——基于明确靶点的药物发现范式占比没变，绝对量在涨。新靶点引入速度：平均每年 12 个（s.d.=5）。2010 年后，内源肽和"其他蛋白"（主要是人细胞表面/免疫蛋白）两类猛增，把整体速度推到每年 15 个。【图3解读】Fig. 3 2000–2024 年药物批准与新靶点趋势。a：蓝线为每年批准药物数（括号内为 MoA 明确的药物数），红线为当年新引入的 MoA 靶点数（括号内为非人源靶点占比）。可见 2008 年（67 个新靶点）、2014 年（68 个）等峰值年份；非人源靶点占比在 2003（28%）、2009（33%）、2012（33%）、2016（31%）等年份较高，反映抗感染药物的脉冲式获批。b：各靶点家族的累计新靶点数——酶（蓝圈）一骑绝尘，25 年逼近 100 个；其他蛋白（黄方块）与内源肽（棕星）2010 年后斜率明显变陡；离子通道、转运体、核激素受体几乎贴地，GPCR 明显放缓、接近饱和；唯一重新加速的是近年来的转运体。四、首发与跟随：EGFR 25年"卷"出14个药一个新靶点首发上市后，往往引来一串跟随者。25 年里最"卷"的两个靶点都是催化受体：· EGFR：2002 年吉非替尼（日本首批）首发，至今 14 个获批药物——10 个小分子 TKI（从吉非替尼到 2024 年的 lazertinib）+ 4 个抗体（西妥昔单抗、帕尼单抗、necitumumab、amivantamab）；· VEGFR2：2005 年索拉非尼首发，已有 13 个药（12 小分子 + 1 抗体）。其他高频跟随靶点：KIT（10 个药）、JAK1/JAK2（各 9 个）、SLC5A2（8 个）、CFTR（7 个）、ALK（7 个）、PD-1（7 个）、TTR（6 个）、MET（6 个）……靶点一旦验证成功，药企立刻蜂拥而上。【图4解读】Fig. 4 2000–2024 年靶点首发与跟随药物全景图。对角线上的图标 = 每年首发的新靶点（图标形状代表蛋白家族：圆=内源肽、叉=其他蛋白、方块叉=GPCR、三角=催化受体、星=酶、加号=转运体、倒三角=离子通道），顶部第一行数字 = 当年新靶点数。对角线上方 = 这些靶点后续的跟随药物（图标大小代表数量），顶部第二行数字 = 该年首发靶点累计引来的跟随药总数（如 2002 年首发 EGFR，累计 36 个跟随药）。对角线下方 = 跟随药物 >5 个的热门靶点标注，如 EGFR（14）、VEGFR2（13）、KIT（10）、JAK1（9）、JAK2（9）、CFTR（7）、SLC5A2（8）、PDCD1（7）、ALK（7）等。颜色（紫→绿）代表距首发的时间。这张图直观呈现两条规律：① 2010 年后首发药物明显增多；② 成功靶点的"跟随效应"极强。五、生物药追平小分子：2023年的历史性交叉小分子独霸天下的时代结束了。对比年度批准数：生物药（mAb、ADC、寡核苷酸、酶、融合蛋白、肽类）在 2023 年追平小分子；按目前趋势，未来几年生物药年度批准数将反超。增长主力是 mAb 和 ADC——2014 年起，mAb/ADC 占到每年生物药批准数的 50–70%。第三根支柱正在崛起：寡核苷酸药物。目前已有 22 个获批，包括 7 个 siRNA（patisiran、givosiran、inclisiran、lumasiran、nedosiran、vutrisiran、fitusiran）、RNase H 降解/空间阻断型 ASO（fomivirsen、mipomersen、volanesorsen、tofersen、inotersen、eplontersen）、剪接调节型 ASO（nusinersen、eteplirsen、golodirsen、viltolarsen、casimersen）、2 个适配体（pegaptanib、avacincaptad pegol），以及 CpG 佐剂 HepB-CpG 和混合寡核苷酸 defibrotide。它们靠 mRNA 降解、剪接调控、基因沉默等机制，攻克了传统药物"够不着"的蛋白和 RNA 转录本。【图5解读】Fig. 5 2000–2024 年获批药物模态趋势。a：每年批准药物按类型的百分比——小分子（红）从约 70% 震荡下行至 58%；生物药（蓝）从 17% 一路爬升到 36%，2023 年（49.1%）首次反超小分子（47.2%），完成历史性交叉；其他模态（黄）维持个位数。b：生物药按子类拆分——mAb/ADC（红）2014 年后放量，2021 年达峰值 18 个；siRNA/ASO（蓝）2016 年起常态化每年 1–4 个；肽类（紫）保持小体量；蛋白/酶/融合蛋白（青）波动中稳定输出。六、疾病版图：肿瘤是主战场，神经领域小分子天下把 1526 个药（90% 的数据集）映射到 WHO ATC 的 14 个一级治疗类别，覆盖 656 个靶点（96%）。由于一个药可有多个 ATC 代码，这张图也体现了药物跨适应症的"多面性"。【图6解读】Fig. 6 桑基图：左列 = 蛋白靶点家族，中列 = 14 个 ATC 一级治疗类别（括号内为靶点数），右列 = 药物类型（小分子/生物药/其他），流带宽度与数量成正比。三个关键信息：① 抗肿瘤及免疫调节剂（L）是最大治疗领域——210 个靶点、322 个药；70% 的催化受体和一半的内源肽都用于肿瘤/免疫；生物药在此占 42%，与小分子（57%）几乎分庭抗礼。② 神经系统（N）第二大——122 个靶点、260 个药，94% 是小分子，主打离子通道和 GPCR。③ 心血管（C）第三——105 个靶点、187 个药，靶点类型更多元（GPCR、酶、离子通道并重）。此外，生物药在激素类（H）占 54% 的药物、61% 的靶点——肽类激素与生物药平台天然适配。整体看，45% 的生物药都用于血液/肿瘤/免疫领域；激酶抑制剂中 78%（94/120）为抗癌药（ATC L01），覆盖 49 个激酶（占全部已成药激酶的 73%）。七、地缘格局：美国说了算？三大监管机构的"存在感"差距巨大：2000 年以来 FDA 批准了 750 个 MoA 明确的药物，EMA 466 个，PMDA 347 个；但三机构全部批准的药只占 27%。去重后共 845 个独特药物，其中超过 80%（616 个）由美国首发。FDA 首批药物中，44%（269 个）在分析期内从未在 EMA 或 PMDA 获批；其余 348 个中，67% 在美国上市一年内获 EMA 批准、38% 获 PMDA 批准。激酶抑制剂 83%（105 个）由 FDA 首批。靶点创新更集中：312 个新靶点中 78% 由 FDA 批准的药物首次验证，EMA、PMDA 各占 11%；26 个非人源（病原体）新靶点中 21 个（81%）FDA 首证；唯一例外是转运体——7 个新靶点 FDA 只占 3 个。【图7解读】Fig. 7 2000 年至 2025 年 6 月三大监管机构批准新药及其靶点的重叠韦恩图。a 药物层面：三家均批准的核心药物池为 224 个；FDA 独有 270 个，远多于 EMA 独有（203）和 PMDA 独有（55）；FDA∩PMDA 54 个、FDA∩EMA 26 个、EMA∩PMDA 14 个。b 靶点层面：三家共享靶点 234 个，FDA 独有靶点 102 个——靶点首发权高度集中于美国。【表1解读】Table 1 2000 年至 2025 年 6 月各监管机构首次上市药物数：FDA 共 617 个（小分子 402、生物药 200、其他 15），EMA 123 个，PMDA 106 个——美国首发的体量约为 EMA 的 5 倍、PMDA 的 6 倍。八、研发周期：生物药比小分子快近一半用 CAS 登记号近似"化合物首次公开"时间，作者测算了从披露到批准的周期：· 小分子：中位 11 年（80% 在 18 年内）；· 生物药：中位 6 年（80% 在 10 年内）——mAb、RNA 类、替代蛋白普遍 5–6 年获批，得益于更高的靶点特异性、更可预测的药理学，以及监管框架的适配；· 肽类例外：平均约 12 年，和小分子相当；· first-in-class 新靶点药物：平均 10 年，80% 在 15 年内——验证全新机制，靶点生物学和临床获益都要从零建立。极端案例两端分化：elexacaftor（2019）和 4 个新冠抗体（2020）当年披露当年获批；也有压箱底 50 年的——clascoterone 和 nifurtimox 约 1970 年登记、约 50 年后才获批；afamelanotide 1981 年登记、2014 年才批。【Box2图解读】化合物登记到上市的时间动态。a：按 CAS 登记年份的药物数量分布——小分子 1983 年后放量，生物药 1995 年后起量。b：从登记到首次批准的年数分布——小分子（红）拖尾很长，生物药（蓝）集中在 0–10 年。c：每个药物的"披露年 vs 批准年"散点（按模态着色）——mAb/ADC（红圆点）与 siRNA/ASO（十字）集中在近年且间隔更短；肽类（紫三角）披露早、批准晚、跨度大。整体：生物药中位 6 年 vs 小分子 11 年，而 first-in-class 药物无论模态，周期都相对一致（约 10 年）。九、中国力量：数量追上来了，靶点创新还在路上综述专门用 Box 3 讨论了中国。对比 2019–2023 年：NMPA 批准 256 个新药，比 FDA 多 5.4%，比 EMA 多 34%，比 PMDA 多 37%——数量上已不落下风。但拆开看靶点创新：216 个药（复方拆分后）中，63 个是三大机构都没批过的"中国独有"，共引入 6 个新靶点：· Aponermin（2023，多发性骨髓瘤）——TRAIL 受体 TNFRSF10A/TNFRSF10B；· 泰它西普 Telitacicept（2021，系统性红斑狼疮）——TNFSF13（APRIL）；· 西格列他钠 Chiglitazar（2021，2型糖尿病）——PPARδ；· 多扎格列艾汀 Dorzagliatin（2022，2型糖尿病）——葡萄糖激酶 GCK；· Ormutivimab（2022，狂犬病）——狂犬病毒 G 蛋白。同期美国引入 59 个新靶点、日本 12 个、欧洲 11 个。另一项肿瘤药分析（2015–2021）更扎心：FDA 批准的 90 个肿瘤药 32% 是 first-in-class，中国为 0。好消息也有两条：美国已批准的药在华获批滞后时间已缩短到 4 年以内；2025 年的 Target Watch 系列已首次把 NMPA 纳入分析——首个组织蛋白酶 L（cathepsin L）靶向药和破伤风毒素靶向药都来自中国。差距在缩小，方向在变好。十、细胞与基因治疗：14个"独占"靶点本文把细胞与基因治疗（CGT）单独拎出来——因为它们打的靶点，传统药物根本碰不了。目前获批 CGT 独占 14 个靶点（如 Lenmeldy/ARSA、Luxturna/RPE65、Roctavian/F8、Casgevy/BCL11A、Zynteglo/HBB、Tecelra/MAGEA4、Skysona/ABCD1 等），分三类逻辑：① 基因替代：ARSA、ABCD1、F8、RPE65、HBB、WAS、OTOF、COL7A1——缺啥补啥；很多要突破血脑/血视网膜屏障，或要求终生、谱系限制性表达；② 基因编辑：BCL11A——CRISPR 敲掉胎儿血红蛋白的转录抑制子，治疗镰刀型贫血（Casgevy）；③ 免疫定向/局部细胞因子：MAGEA4（TCR-T 细胞）、ACPP（树突细胞疫苗）、CSF2/IFNA2/CNTF（溶瘤病毒、腺病毒、包囊细胞局部递送）。这些靶点的共同点：胞内定位、免疫豁免区、或需要持续表达——小分子、抗体、寡核苷酸三不支持。这正是 CGT 的独特生态位。十一、写在最后：下一个25年25 年前我们以为基因组测完，靶点就应有尽有；25 年后才发现，真正稀缺的从来不是靶点清单，而是把靶点变成药的技术。下一个黄金靶点，也许不在基因组的某个角落，而在某种新模态的能力边界上。

100 项与 Elexacaftor 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D11507	Elexacaftor	-	DB15444

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适应症	最高研发状态	国家/地区	公司	日期
囊性纤维化	临床2期	美国	Vertex Pharmaceuticals, Inc.	2017-01-23

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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


ARVO2026	N/A	VEGF \| CFTR	439	Netarsudil	餘鑰壓遞窪淵範簾衊鹹(醖夢夢築餘積餘網鹹廠) = 蓋醖鬱構願選觸齋壓網觸襯蓋鹽窪蓋鹹構廠膚 (鑰糧醖製壓範顧襯膚糧 )	积极	2026-05-03
				Ranibizumab	餘鑰壓遞窪淵範簾衊鹹(醖夢夢築餘積餘網鹹廠) = 膚範蓋鑰願築鬱繭願淵觸襯蓋鹽窪蓋鹹構廠膚 (鑰糧醖製壓範顧襯膚糧 )
ATS2025	N/A	-	-	Elexacaftor	觸蓋遞網遞鹽觸觸顧齋(鬱壓廠鬱糧顧選積衊醖) = 顧簾範憲鹽簾繭遞憲觸鑰製蓋夢餘範艱鹽觸壓 (鹹淵範觸顧廠願襯壓艱 )	-	2025-05-16
				Tezacaftor	觸蓋遞網遞鹽觸觸顧齋(鬱壓廠鬱糧顧選積衊醖) = 構鏇齋襯醖夢構鬱鹽簾鑰製蓋夢餘範艱鹽觸壓 (鹹淵範觸顧廠願襯壓艱 )
ERS2023	N/A	囊性纤维化	156	Elexacaftor, Tezacaftor and Ivacaftor (ETI)	艱觸襯構糧範餘願鑰憲(憲艱淵醖憲積齋積憲齋) = 夢構製餘簾顧糧淵鏇壓鹹廠範築窪艱築壓壓觸 (積製窪鹽淵繭遞淵衊遞 ) 更多	积极	2023-09-09
ERS2023	N/A	囊性纤维化	50	Elexacaftor/Tezacaftor/Ivacaftor	膚簾蓋遞窪選鹹齋鬱獵(齋積獵製餘淵積範築鏇) = Patients with a low pre-treatment RV/TLC ratio showed higher responses after 12 months of ETI 網壓艱窪醖選鬱鏇糧鹹 (繭糧膚觸廠鬱簾廠鑰觸 )	积极	2023-09-09
				Placebo
ERS2023	N/A	囊性纤维化	45	Elexacaftor/Tezacaftor/Ivacaftor (ETI)	構簾襯遞衊憲願憲醖獵(鹹夢襯蓋夢鹹壓積廠艱) = One patient was diagnosed with bipolar disorder 窪繭蓋糧廠蓋憲膚鹽鹹 (窪鑰鹽糧窪網鑰網鏇憲 ) 更多	不佳	2023-09-09
ERS2023	N/A	囊性纤维化	15	Elexacaftor/Tezacaftor/Ivacaftor (ETI)	膚鹽繭壓廠顧選鹽餘遞(鬱鏇遞齋鏇鬱網衊簾獵) = 艱壓艱觸艱願顧顧願壓衊獵憲願願鹹範鬱製蓋 (淵觸憲鬱製衊鹹壓鑰鬱 )	积极	2023-09-09