Open-Label, Single-Sequence Study to Evaluate the Effects of Darunavir/Ritonavir and/or Etravirine on the Pharmacokinetics of GSK3640254 and the Effects of GSK3640254 on the Pharmacokinetics of Darunavir/Ritonavir and/or Etravirine in Heathy Adults

This is an open-label, single-sequence, multiple-dose, 3 cohort study to investigate the effects of DRV/RTV and/or ETR on the pharmacokinetics (PK) of GSK3640254 and the effects of GSK3640254 on the PK of DRV/RTV and/or ETR. This study will aid in understanding these interactions and resulting changes in exposure (if any) when given in combination with GSK3640254.

开始日期2020-10-28

申办/合作机构

ViiV Healthcare Ltd.

NCT04273165

/ Completed临床2期IIT

A Phase 2 Clinical Trial to Test the Safety and Efficacy of Etravirine in Friedreich Ataxia Patients

A drug repositioning effort provided evidence supporting the possible use of Etravirine, a drug approved for the treatment of HIV infections in patients starting from 2 years of age, as a treatment for FA. We found that Etravirine is able to increase Frataxin protein both in vitro - in cells derived from FA patients - and in vivo - in the heart and skeletal muscle of Frataxin-deficient YG8 mice. Because of these findings, and since Etravirine displays a generally favorable safety profile, we plan to launch an open-label, phase 2 clinical trial aimed at assessing the safety and efficacy of Etravirine in FA patients. We aim at recruiting 30 FA patients. 15 will be treated with Etravirine for 4 months at 200 mcg/day and 15 will be treated with Etravirine for 4 months at 400 mg/day. Efficacy primary endpoint will be represented changes in peak VO2 as measured by incremental cycle ergometer exercise test. Secondary endpoints will include maximal workload, SARA score, cardiac measures, Frataxin protein levels in peripheral blood mononuclear cells and molecular analysis of Frataxin mRNA translation efficiency. Complete sets of data will be collected 4 months before the start of the treatment (T -4), at the start (T0), after 2 months (T2), at the end of the treatment (T4) and 4 months after the termination of the treatment (T8).

开始日期2020-09-17

申办/合作机构

Università degli Studi di Roma Tor Vergata

NCT04208373

/ Completed临床1期

A Phase 1, Open-label, Fixed-sequence, 2-Panel Study to Assess the Effects of Itraconazole and Etravirine on the Single-dose Pharmacokinetics of JNJ-64417184 in Healthy Adult Subjects

The main purpose of this study is to evaluate the effects of itraconazole or etravirine on the single-dose pharmacokinetics (PK) of JNJ 64417184 in healthy adult participants.

开始日期2019-12-20

申办/合作机构

Janssen Research & Development LLC

100 项与依曲韦林相关的临床结果

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100 项与依曲韦林相关的转化医学

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100 项与依曲韦林相关的专利（医药）

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1,542

项与依曲韦林相关的文献（医药）

2026-06-01·THROMBOSIS RESEARCH

Real-world practices in the management of pediatric iliofemoral deep vein thrombosis: Results of the ELITE-Kids survey

Article

作者: Amankwah, E K ; Betensky, M ; Jaffray, J ; Bredeck, A ; Branchford, B ; Mir, D ; Vedantham, S ; Goldenberg, N A ; Al-Ghafry, M

BACKGROUND:

Pediatric anticoagulation trials have advanced evidence-based management of pediatric venous thromboembolism, but evidence is limited on the use of endovascular thrombus removal (ETR), particularly regarding clinical indications, modality selection, anticoagulant and thrombolytic dosing, safety, efficacy, and long-term outcomes. This particularly pertains to iliofemoral deep vein thrombosis (IF-DVT), commonly considered for ETR.

OBJECTIVE:

To characterize the current perspectives of pediatric hematologists on the use of ETR for managing pediatric IF-DVT via an electronic survey. We hypothesized substantial variability on indications, preferred modalities, and anticoagulation management.

METHODS:

A cross-sectional electronic survey was developed by pediatric hematologists and interventional radiologists as part of the ELITE-Kids (Endovascular Limb Intervention for Thrombosis Eradication in Kids) study and distributed via the Children's Healthcare Advancements in Thrombosis (CHAT) consortium.

RESULTS:

Thirty-five complete responses (58% response rate) were analyzed, with nearly all respondents considering ETR appropriate for children with severe, symptomatic IF-DVT. Pharmacomechanical and catheter-directed thrombolysis were preferred over mechanical thrombectomy (MT), although MT was associated with acceptable outcomes. Interventional radiologists were the primary proceduralists, with decisions on timing and iliac stent placement occasionally deferred to them. While there was consensus on concurrent anticoagulation during thrombolysis, the duration and intensity of outpatient antithrombotic agents varied greatly.

CONCLUSION:

Significant heterogeneity exists on the use of ETR and adjunct antithrombotic agents for pediatric IF-DVT among pediatric hematologists. This is likely a reflection of the paucity of pediatric-specific evidence-based guidelines, underscoring the need for pediatric cohort studies to strengthen management decisions.

2026-04-01·Neurology and Therapy

From Stroke to Strength: The Role of Exercise in Managing Hypertension and Lipid Profiles

Review

作者: Huang, Mingyu ; Yuan, Ruimin ; Han, Zhongyu ; Xiao, Renyan ; Li, Pei ; Guo, Hong ; Jia, Peng ; Jin, Song ; Liu, Haichao ; Gong, Meng ; Liu, Zhixiang

Secondary stroke prevention focuses on managing vascular risk factors such as hypertension, hyperglycemia, and dyslipidemia. However, the impact of exercise training regimens (ETR) on these factors post-stroke remains unclear. We conducted a network meta-analysis (NMA) to compare the effects of different ETR on vascular risk factors and adverse events in patients following stroke or transient ischemic attacks (TIA). We performed a systematic review following PRISMA criteria, searching multiple databases until March 2024. The outcomes of interest included systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), fasting blood glucose (FBG), and body mass index (BMI). A Bayesian network meta-analysis approach was used to estimate mean differences (MD) and 95% credible intervals (CrI). We analyzed 20 randomized clinical trials involving 1653 patients. Moderate intensity continuous training (MICT) and comprehensive training program (CTP) showed the greatest effects on SBP and DBP. Resistance training (RT) was most effective for improving lipid profiles. ETR had no significant effect on post-stroke FBG and BMI. For secondary stroke prevention, MICT and CTP may be beneficial for managing hypertension, while RT could be the primary strategy for improving lipid profiles.Trial Registration: CRD42024554934.

2026-03-01·AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Late-in-life treadmill training mitigates gut microbiome imbalances and cardiovascular disease risk in mice

Article

作者: Wankhade, Umesh D. ; Anandh Babu, Pon Velayutham ; Park, Seul-Ki ; Mookherjee, Sohom ; Robeson, Michael S. ; Satheesh Babu, Adhini Kuppuswamy ; Zhong, Ying ; Petersen, Chrissa ; Symons, J. David ; Cho, Jae Min ; Jalili, Thunder ; Hansen, Michele

It is unknown whether exercise training, if started late-in-life, reestablishes a beneficial and cooperative intestinal microbiome. Here we demonstrate that a 12-wk treadmill running program in older mice rejuvenates the gut microbiome and attenuates markers of cardiovascular disease (CVD) risk. Notably, specific microbial taxa correlate with activity-induced improvements in overall myocardial performance and inflammation, highlighting the importance of gut health on CVD and illustrating the restorative benefits that can be attained from a low-cost lifestyle intervention.

项与依曲韦林相关的新闻（医药）

2026-06-10

·北京医学感染与传染研究

抗菌化疗杂志81卷 1-6期

Journal of Antimicrobial Chemotherapy Volume 81, Issue 1抗菌化疗杂志81卷 1期 https://academic.oup.com/jac/issue 50th Anniversary Collection（50周年纪念合集） Review（综述） 1 Artificial intelligence for improving decision-making in bacterial infection management: a narrative review 人工智能在改善细菌感染治疗决策中的应用：一项叙述性综述 Anisia Talianu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf470, https://doi.org/10.1093/jac/dkaf470 Reviews（综述） 2 Evolving landscape of methicillin-resistant Staphylococcus pseudintermedius: the emergence of new epidemic waves across Europe, Asia and North America 耐甲氧西林中间型葡萄球菌的演变格局：欧洲、亚洲和北美洲新流行浪潮的出现 Lillian Rose Giarratana and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf340, https://doi.org/10.1093/jac/dkaf340 3 Azithromycin resistance in non-typhoidal Salmonella: a review 非伤寒沙门氏菌对阿奇霉素的耐药性：综述 Zhe Zhu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf341, https://doi.org/10.1093/jac/dkaf341 4 Antibiotic pharmacodynamics: from MIC to advanced metrics and their applications 抗生素药效动力学：从最低抑菌浓度到高级指标及其应用 Malin Andersson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf374, https://doi.org/10.1093/jac/dkaf374 5 Progress in the study of drug resistance mechanism of Bacillus cereus 蜡样芽孢杆菌耐药机制研究进展 Yuhang Zhang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf399, https://doi.org/10.1093/jac/dkaf399 6 The curious constraints on clofazimine 氯法齐明的奇特限制 Maple Goh and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf430, https://doi.org/10.1093/jac/dkaf430 7 Antiplasmid systems: a novel strategy to combat antibiotic resistance 抗质粒系统：对抗抗生素耐药性的新策略 Mohd Asim and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf472, https://doi.org/10.1093/jac/dkaf472 Systematic Review（系统综述） 8 Coccidioidomycosis in Europe: a systematic literature review of epidemiology, treatment and outcomes 欧洲球孢子菌病：流行病学、治疗和预后的系统文献综述 Priya Shastri and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf407, https://doi.org/10.1093/jac/dkaf407 9 Systematic review of antimicrobial pharmacokinetic/pharmacodynamic indices in murine thigh and hollow fibre dose fractionation studies analysed with a standard method 用标准方法分析小鼠大腿和空心纤维剂量分次研究中的抗菌药物药代动力学/药效动力学指数的系统综述 Najla Alabdulkarim and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf446, https://doi.org/10.1093/jac/dkaf446 Virtual Roundtable（虚拟圆桌会议） 10 Procalcitonin in the management of lower respiratory tract infection and sepsis 降钙素原在下呼吸道感染和败血症治疗中的应用 Ramy H Elshaboury and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf298, https://doi.org/10.1093/jac/dkaf298 Original Research（论著） 11 Model-based assessment of letermovir pharmacokinetics in allogeneic haematopoietic stem cell transplant recipients 来特莫韦在异基因造血干细胞移植受者中药代动力学的基于模型的评估 Chrisoula Tahtsidou and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf427, https://doi.org/10.1093/jac/dkaf427 12 In vitro exebacase (CF-301) activity against methicillin-susceptible or methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci strains isolated from patients with infective endocarditis 体外试验评估依拉环素（CF-301）对甲氧西林敏感或甲氧西林耐药金黄色葡萄球菌及凝固酶阴性葡萄球菌（从感染性心内膜炎患者中分离）的活性 María-Alexandra Cañas and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf435, https://doi.org/10.1093/jac/dkaf435 13 Evaluation of subcutaneous amoxicillin/clavulanic acid pharmacokinetics as an alternative to the intravenous route in older patients—the PhASAge Study 评估皮下注射阿莫西林/克拉维酸药代动力学作为老年患者静脉给药替代方案——PhASAge研究 Nicolas Grégoire and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf381, https://doi.org/10.1093/jac/dkaf381 14 Real-life use of isavuconazole in Spanish children and adolescents 西班牙儿童和青少年中艾沙康唑的实际使用情况 Natalia Mendoza-Palomar and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf394, https://doi.org/10.1093/jac/dkaf394 15 No pharmacovigilance signal of intracranial hypertension associated with glycylcyclines: a FAERS-based disproportionality analysis 基于FAERS数据库的不成比例性分析：未发现甘氨酰环素类与颅内高压相关的药物警戒信号 Slobodan M Jankovic and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf395, https://doi.org/10.1093/jac/dkaf395 16 Posaconazole enteral tube administration in adults: pharmacokinetic target attainment of oral suspension compared with crushed delayed-release tablet 成人经肠内营养管给予泊沙康唑：口服混悬液与碾碎的缓释片的药代动力学目标达成情况比较 Nirjan Bhattarai and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf396, https://doi.org/10.1093/jac/dkaf396 17 Characterizing CYP3A4-mediated drug interactions: a fixed-sequence pharmacokinetic Chinese study of posaconazole and ruxolitinib in haematological malignancies CYP3A4介导的药物相互作用特征：一项关于泊沙康唑和鲁索替尼在血液系统恶性肿瘤中的固定序列药代动力学中国研究 Beibei Liang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf398, https://doi.org/10.1093/jac/dkaf398 18 Differences in prescription for impetigo and cellulitis across years in three European countries 三个欧洲国家不同年份脓疱病和蜂窝织炎的处方差异 Thomas Bettuzzi and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf400, https://doi.org/10.1093/jac/dkaf400 19 β-Lactam concentrations monitored in the early phase of community-acquired sepsis in the intensive care unit 重症监护室社区获得性脓毒症早期阶段监测的β-内酰胺浓度 Karolina Liljedahl Prytz and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf401, https://doi.org/10.1093/jac/dkaf401 20 Enhanced antimycobacterial efficacy of simulated inhaled clofazimine versus oral clofazimine in combination with azithromycin and ethambutol in a hollow-fiber system 在空心纤维系统中，模拟吸入氯法齐明与口服氯法齐明联合阿奇霉素和乙胺丁醇的抗结核分枝杆菌疗效增强比较 Jelmer Raaijmakers and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf402, https://doi.org/10.1093/jac/dkaf402 21 Identification of antimicrobial resistance genes in Escherichia coli through network diffusion 通过网络扩散法鉴定大肠杆菌中的抗生素耐药基因 Anis Mansouri and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf404, https://doi.org/10.1093/jac/dkaf404 22 Preclinical evaluation of epetraborole in the hollow fibre system model of Mycobacterium abscessus lung disease 依培硼罗在脓肿分枝杆菌肺病空心纤维系统模型中的临床前评估 Sanjay Singh and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf405, https://doi.org/10.1093/jac/dkaf405 23 The β-lactamase inhibitor concentration-dependent minimum inhibitory concentration (MICcBLI) as methodology to assess the pharmacokinetic/pharmacodynamic relationship of piperacillin/tazobactam for dosing optimization β-内酰胺酶抑制剂浓度依赖性最低抑菌浓度（MICcBLI）作为评估哌拉西林/他唑巴坦药代动力学/药效动力学关系以优化给药的方法 Malin Andersson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf406, https://doi.org/10.1093/jac/dkaf406 24 Unravelling the triad of penicillin-binding proteins, β-lactamase activity, and mRNA dynamics in Pseudomonas aeruginosa AmpC induction 解析铜绿假单胞菌AmpC诱导过程中青霉素结合蛋白、β-内酰胺酶活性和mRNA动态的三元关系 Maria Montaner and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf408, https://doi.org/10.1093/jac/dkaf408 25 Unnoticed spread of linear VanA-plasmids in vancomycin-variable Enterococcus faecium strains across different regions: a diagnostics challenge 不同地区万古霉素可变型粪肠球菌菌株中线性VanA质粒的未被察觉的传播：一项诊断挑战 Ana C Almeida-Santos and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf409, https://doi.org/10.1093/jac/dkaf409 26 Switching from etravirine to doravirine in virologically suppressed people with HIV: results from the French multicentre SWEED observational study 在病毒学抑制的HIV感染者中从依曲韦林切换至多拉韦林：法国多中心SWEED观察性研究的结果 Romain Palich and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf410, https://doi.org/10.1093/jac/dkaf410 27 HIV-1 drug resistance among pregnant and breastfeeding mothers and its association with paediatric HIV infections in the Dolutegravir era in Uganda 乌干达多替拉韦时代孕产妇及哺乳期母亲中HIV-1耐药情况及其与儿童HIV感染的关联 Anne Kapaata and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf411, https://doi.org/10.1093/jac/dkaf411 28 Outpatient antibiotic prescribing for medically attended respiratory syncytial virus, influenza, or human metapneumovirus illness among high-risk adults in rural Wisconsin, United States 美国威斯康星州农村地区高风险成人因呼吸道合胞病毒、流感或人偏肺病毒感染就诊时的门诊抗生素处方情况 Sarah C J Jorgensen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf412, https://doi.org/10.1093/jac/dkaf412 29 Omadacycline as a drug candidate for Mycobacterium avium infections: in vitro insights on single and combination therapies 奥马环素作为鸟分枝杆菌感染候选药物：单药及联合治疗的体外研究 Saskia E Mudde and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf413, https://doi.org/10.1093/jac/dkaf413 30 Post-pandemic trends in Streptococcus pneumoniae serotype epidemiology and antibiotic susceptibility in adults with invasive and non-invasive pneumococcal disease in the USA (2022–2023) 后疫情时代美国成人侵袭性与非侵袭性肺炎链球菌病血清型流行病学及抗生素敏感性趋势（2022-2023） Mekki F Bensaci and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf414, https://doi.org/10.1093/jac/dkaf414 31 Benznidazole pharmacokinetics in patients with chronic Chagas disease: association with demographic factors and adverse drug reactions 慢性恰加斯病患者苯芴醇药代动力学：与人口统计学因素及药物不良反应的关联 Gabriel P E Silveira and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf416, https://doi.org/10.1093/jac/dkaf416 32 Acquired antimicrobial resistance genes in Bordetella Species: a global genomic analysis 博德特氏菌属中获得的抗菌药物耐药基因：全球基因组分析 Biao Tang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf418, https://doi.org/10.1093/jac/dkaf418 33 Machine learning for personalized antimicrobial susceptibility breakpoints: (Adaptive clinical breakpoint interpretation) 基于机器学习的个性化抗菌药物敏感性折点制定（自适应临床折点解释） Yinzheng Zhong and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf419, https://doi.org/10.1093/jac/dkaf419 34 Multicentre investigation of Wickerhamomyces anomalus fungemia in India: emerging resistance and mechanistic insights 印度异常威克汉姆酵母菌血症的多中心研究：新发耐药性及机制洞察 Shristi Verma and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf420, https://doi.org/10.1093/jac/dkaf420 35 Reducing aztreonam/avibactam waste: insights from Monte Carlo simulations 减少氨曲南/阿维巴坦浪费：蒙特卡洛模拟的启示 Yeleen Fromage and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf421, https://doi.org/10.1093/jac/dkaf421 36 Nanoparticle-based co-delivery of ciprofloxacin and meropenem enhances synergistic activity against multidrug-resistant hypervirulent Klebsiella pneumoniae clinical isolates 基于纳米颗粒的环丙沙星与美罗培南共递送可增强对多重耐药高毒力肺炎克雷伯菌临床分离株的协同活性 Reham Mostafa and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf422, https://doi.org/10.1093/jac/dkaf422 37 Development of population pharmacokinetic models of total and free piperacillin in critically ill children and young adults for Monte Carlo simulations and model-informed precision dosing 危重症儿童及青年总游离哌拉西林群体药代动力学模型开发：用于蒙特卡洛模拟及模型引导的精准给药 Sonya Tang Girdwood and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf423, https://doi.org/10.1093/jac/dkaf423 38 Reaching the target: time and dose required to achieve target vancomycin plasma concentrations in admitted patients 达标分析：住院患者达到目标万古霉素血浆浓度所需的时间与剂量 W Töpfer and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf424, https://doi.org/10.1093/jac/dkaf424 39 Notable transmitted HIV drug resistance among people who inject drugs in Pakistan 巴基斯坦注射毒品人群中显著传播的HIV耐药性 Stephanie Melnychuk and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf425, https://doi.org/10.1093/jac/dkaf425 40 Synergistic but clinically unattainable: amoxicillin/ceftriaxone combination against ampicillin-susceptible Enterococcus faecium 协同但临床难以实现：阿莫西林/头孢曲松联合对氨苄西林敏感粪肠球菌的体外活性 Ahmed Ashrin and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf426, https://doi.org/10.1093/jac/dkaf426 41 Pharmacodynamic studies of taniborbactam (VNRX-5133) combined with cefepime against β-lactamase–producing Gram-negative bacteria in a neutropenic murine thigh infection model 中性粒细胞减少小鼠大腿感染模型中他尼硼巴坦（VNRX-5133）联合头孢吡肟对产β-内酰胺酶革兰氏阴性菌的药效动力学研究 Panagiota-Christina Georgiou and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf431, https://doi.org/10.1093/jac/dkaf431 42 Epidemiology and treatment of endocarditis secondary to Enterobacterales other than Serratia spp. 非塞拉蒂亚属肠杆菌目细菌所致心内膜炎的流行病学及治疗 Clayton F Hausberger and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf432, https://doi.org/10.1093/jac/dkaf432 43 Enhanced activity of apramycin and apramycin-based combinations against Mycobacteroides abscessus 阿普拉霉素及其组合对脓肿分枝杆菌的增强活性 Yanqin Huang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf433, https://doi.org/10.1093/jac/dkaf433 44 Efflux-mediated multidrug resistance mechanism in Trichophyton indotineae and Trichophyton rubrum; role of ABC transporters and MFS gene 印度毛癣菌与红色毛癣菌中由ABC转运蛋白和MFS基因介导的流出泵型多重耐药机制 Dipika Shaw and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf434, https://doi.org/10.1093/jac/dkaf434 45 Sphingobacterium spp. as intrinsic producers of SPI Ambler class B metallo-β-lactamases 鞘氨醇杆菌属作为SPI Ambler B类金属β-内酰胺酶的固有产生者 Delphine Girlich and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf436, https://doi.org/10.1093/jac/dkaf436 46 Global phylogeography and genomic characterization of blaNDM-1-positive carbapenem-resistant Acinetobacter soli blaNDM-1阳性碳青霉烯耐药溶胶阿卡净菌的全球系统发育地理学及基因组特征 Pengpeng Min and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf437, https://doi.org/10.1093/jac/dkaf437 47 Pharmacokinetics and tolerability of one-month daily rifapentine for latent tuberculosis treatment in haemodialysis patients 血液透析患者潜伏性结核治疗中每月一次每日利福喷丁的药代动力学及耐受性 Thornthun Ueaphongsukkit and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf439, https://doi.org/10.1093/jac/dkaf439 48 In vitro susceptibility of cefepime-enmetazobactam, cefepime-taniborbactam and cefepime-zidebactam towards carbapenemase-producing Enterobacterales 头孢吡肟-恩美他唑巴坦、头孢吡肟-他尼硼巴坦及头孢吡肟-齐德巴坦对产碳青霉烯酶肠杆菌目的体外敏感性 Marion Dutkiewicz and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf440, https://doi.org/10.1093/jac/dkaf440 49 In vitro efficacy of sulbactam/durlobactam combined with β-lactam antibiotics in Australian Mycobacterium abscessus isolates 舒巴坦/杜洛巴坦联合β-内酰胺类抗生素对澳大利亚脓肿分枝杆菌分离株的体外疗效 Kirby Patterson-Fahy and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf441, https://doi.org/10.1093/jac/dkaf441 50 Harnessing CRISPR–Cas9 and CRISPRi systems to reverse antibiotic resistance in a clinical multidrug-resistant Escherichia coli isolate 利用CRISPR-Cas9及CRISPRi系统逆转临床多重耐药大肠杆菌分离株的抗生素耐药性 Ruonan Zhao and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf442, https://doi.org/10.1093/jac/dkaf442 51 Cotrimoxazole in the intensive care unit: an impossible task for the fixed association in real life? 重症监护室中复方磺胺甲噁唑的应用：固定组合在现实中的不可行性？ Manon Launay and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf443, https://doi.org/10.1093/jac/dkaf443 52 National representative survey of pretreatment HIV drug resistance in Colombia: analysis of antiretroviral resistance-associated mutations using next-generation sequencing 哥伦比亚全国代表性调查：基于下一代测序的抗逆转录病毒耐药相关突变分析 Ernesto Martínez-Buitrago and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf444, https://doi.org/10.1093/jac/dkaf444 53 A model-based comparison of dose reduction strategies for fixed-dose dolutegravir-containing regimens 基于模型的含固定剂量多替拉韦方案减量策略比较 Laura Dickinson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf445, https://doi.org/10.1093/jac/dkaf445 54 Therapeutic drug monitoring and target attainment of unbound flucloxacillin in hospitalized patients with measured MICs (FLUTE) 住院患者中游离氟氯西林的治疗药物监测及目标达成情况（基于实测最低抑菌浓度的FLUTE研究） Pjotr P Temme and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf447, https://doi.org/10.1093/jac/dkaf447 55 Nirmatrelvir-ritonavir addition to acute care formulary: a retrospective, multi-centre evaluation of quantitative economic and qualitative clinical outcomes 奈玛特韦/利托那韦纳入急症治疗目录：一项多中心回顾性评估定量经济与定性临床结果的研究 Jose Valdes Ledesma and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf448, https://doi.org/10.1093/jac/dkaf448 56 Local antibiotic resistance surveillance in nursing homes using lot quality assurance sampling: a feasibility study 采用批量质量保证抽样法对养老院进行本地抗生素耐药性监测的可行性研究 Sacha Kuil and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf451, https://doi.org/10.1093/jac/dkaf451 57 High in vitro activity of the novel antimicrobial gepotidacin against Neisseria gonorrhoeae isolates in eight WHO Enhanced Gonococcal Antimicrobial Surveillance Programme countries in three WHO regions, 2021–24 2021-2024年，在世卫组织三个区域的八个世卫组织增强淋球菌抗菌药物监测计划国家中，新型抗菌药物吉皮达星对淋病奈瑟菌分离株的体外活性较高 Josefine Ahlstrand and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf452, https://doi.org/10.1093/jac/dkaf452 58 Despite increasing use of integrase inhibitors to treat HIV infection, resistance to this class remains stable 尽管整合酶抑制剂用于治疗HIV感染的使用量不断增加，但此类药物的耐药性仍保持稳定 Cathia Soulie and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf454, https://doi.org/10.1093/jac/dkaf454 59 Fine-needle aspiration in infected necrotizing pancreatitis in the delayed intervention era: a post hoc analysis of safety, microbiological yield and therapeutic implications 延迟干预时代感染性坏死性胰腺炎的细针穿刺抽吸术：安全性、微生物学检出率及治疗意义的事后分析 Hannah S Pauw and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf455, https://doi.org/10.1093/jac/dkaf455 60 β-Lactam dosing in critically ill children: predictors for target non-attainment 危重症儿童β-内酰胺类药物给药：未达目标浓度的预测因素 Stef Schouwenburg and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf457, https://doi.org/10.1093/jac/dkaf457 61 Co-administration of triazoles with calcineurin or mammalian target of rapamycin inhibitors in solid organ transplant patients hospitalized with invasive aspergillosis 实体器官移植患者合并侵袭性曲霉病住院时三唑类药物与钙调磷酸酶抑制剂或哺乳动物雷帕霉素靶蛋白抑制剂的联合用药情况 Barbara Alexander and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf461, https://doi.org/10.1093/jac/dkaf461 62 In vitro selection of cefiderocol-resistant mutants in Acinetobacter baumannii harbouring the most common carbapenemase genes 携带最常见碳青霉烯酶基因的鲍曼不动杆菌中头孢地尔耐药突变体的体外筛选 Otávio Hallal Ferreira Raro and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf462, https://doi.org/10.1093/jac/dkaf462 63 Preventing resistance development in infections by OXA β-lactamase-producing Pseudomonas aeruginosa: correlating clinical outcomes with hollow-fibre model input 预防产OXA β-内酰胺酶铜绿假单胞菌感染耐药性的产生：将临床结局与中空纤维模型输入相关联 María M Montero and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf464, https://doi.org/10.1093/jac/dkaf464 64 A national pilot community pharmacy–led urinary tract infection service: clinical and patient-reported outcomes from 9077 consultations 全国社区药房主导的尿路感染服务试点项目：9077次咨询的临床结局和患者报告结局 Efi Mantzourani and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf466, https://doi.org/10.1093/jac/dkaf466 65 Towards enhanced translational value: preclinical drug activity testing against actively multiplying, nutrient-starved and pellicle biofilm-embedded Mycobacterium abscessus 提高转化价值：针对活跃增殖、营养匮乏和生物膜包裹的脓肿分枝杆菌进行临床前药物活性测试 Henriëtte M Meliefste and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf468, https://doi.org/10.1093/jac/dkaf468 Research Letters（研究快报） 66 Novel multiresistance transposon Tn7731 in bovine Pasteurella multocida from Germany 德国牛源多杀性巴氏杆菌中新型多重耐药转座子Tn7731 Henrike Krüger-Haker and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf336, https://doi.org/10.1093/jac/dkaf336 67 Efficacy of eravacycline in difficult-to-treat (DTR) Acinetobacter baumannii bacteraemia in ICU: a case report 厄他培南治疗重症监护病房难治性鲍曼不动杆菌菌血症的疗效：一例病例报告 Monica Melchio and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf347, https://doi.org/10.1093/jac/dkaf347 68 Possible increased risk of Epstein–Barr virus (EBV) infection and post-transplant lymphoproliferative disease (PTLD) in letermovir-exposed haematopoietic cell transplantation recipients 来特莫韦暴露的造血细胞移植受者中EB病毒感染和移植后淋巴增殖性疾病风险可能增加 Jose F Camargo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf348, https://doi.org/10.1093/jac/dkaf348 69 Dalbavancin dosing in a severely underweight woman with prosthetic valve endocarditis: the critical role of proactive therapeutic drug monitoring 达巴万星在严重体重不足人工瓣膜心内膜炎女性患者中的给药：主动治疗药物监测的关键作用 Ambra Barco and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf365, https://doi.org/10.1093/jac/dkaf365 70 Cefazolin-induced seizures in a haemodialysis patient with elevated serum and cerebrospinal fluid concentrations: a case report 血液透析患者头孢唑林血清和脑脊液浓度升高诱发癫痫：一例病例报告 Kohei Hasegawa and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf373, https://doi.org/10.1093/jac/dkaf373 71 Retrospective analysis of pharmacological therapeutic monitoring of caspofungin in patients undergoing continuous renal replacement therapy using polyacrylonitrile membranes 使用聚丙烯腈膜进行连续性肾脏替代治疗的患者中卡泊芬净药代动力学治疗监测的回顾性分析 Antoine Hérault and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf390, https://doi.org/10.1093/jac/dkaf390 72 Diffusion of OXA-48- and NDM-5-producing Klebsiella pneumoniae ST383 clone in Central Italy 产OXA-48和NDM-5的肺炎克雷伯菌ST383克隆在意大利中部的传播 Gloria D’Achille and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf397, https://doi.org/10.1093/jac/dkaf397 73 Durability of lenacapavir in viremic heavily treatment-experienced people with HIV: real-world data from the PRESTIGIO Registry 来那卡帕韦在病毒载量阳性且接受过大量抗逆转录病毒治疗的HIV感染者中的持久性：来自PRESTIGIO登记处的现实数据 Tommaso Clemente and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf415, https://doi.org/10.1093/jac/dkaf415 74 Co-carriage of the oxazolidinone resistance genes cfr and optrA in a linezolid-resistant Staphylococcus rostri isolate from a pig-farm worker 猪场工人利奈唑胺耐药猪鼻支原体分离株中噁唑烷酮类耐药基因cfr和optrA的共携带情况 Gi Yong Lee and Soo-Jin Yang Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf428, https://doi.org/10.1093/jac/dkaf428 75 Importance of reviewing the package insert from gradient strip manufacturers 梯度扩散法药敏纸片生产商说明书审阅的重要性 Mandy Wootton and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf429, https://doi.org/10.1093/jac/dkaf429 76 One resistance gene, many transposons: repeated formation of compound and pseudo-compound transposons carrying the aphA1 kanamycin and neomycin resistance gene 一个耐药基因，多个转座子：携带aphA1卡那霉素和新霉素耐药基因的复合及假复合转座子的重复形成 Christopher J Harmer and Ruth M Hall Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf450, https://doi.org/10.1093/jac/dkaf450 77 Absence of lymphogranuloma venereum among men who have sex with men on PrEP receiving doxycycline postexposure prophylaxis 接受暴露后多西环素预防性治疗的暴露前预防用药男男性行为者中未发现性病淋巴肉芽肿 Cristina Gómez-Ayerbe and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf456, https://doi.org/10.1093/jac/dkaf456 78 In vitro activity of gepotidacin against Chlamydia trachomatis 吉皮达星对沙眼衣原体的体外活性 Arabella Touati and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf460, https://doi.org/10.1093/jac/dkaf460 Journal of Antimicrobial Chemotherapy Volume 81, Issue 2抗菌化疗杂志 81卷 2期 https://academic.oup.com/jac/issue Viewpoints（观点） 1 Long-acting glycopeptides: what are the barriers to access in patients who need them most, and how can they be overcome? 长效糖肽类：最需要它们的患者获取药物的障碍有哪些，如何克服？ Aleece MacPhail and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf471, https://doi.org/10.1093/jac/dkaf471 2 Redefining antifungal prophylaxis in acute leukaemia in the era of targeted therapies 靶向治疗时代急性白血病抗真菌预防的重新定义 Marcio Nucci and Johan Maertens Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag010, https://doi.org/10.1093/jac/dkag010 Reviews（综述） 3 Research progress on resistance mechanisms and clinical efficacy of tigecycline against Klebsiella pneumoniae 替加环素对肺炎克雷伯菌的耐药机制及临床疗效研究进展 Meilin Wu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf504, https://doi.org/10.1093/jac/dkaf504 4 Liposomal amphotericin B and renal safety: review of the evidence and clinical considerations 两性霉素B脂质体与肾脏安全性：证据回顾及临床考量 Johan Maertens and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf473, https://doi.org/10.1093/jac/dkaf473 5 Strategies for mitigating severe COVID-19 in patients with haematological malignancy during the omicron era 奥密克戎时代减轻血液系统恶性肿瘤患者严重新冠肺炎的策略 Keiji Okinaka and Joshua T Schiffer Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf489, https://doi.org/10.1093/jac/dkaf489 Systematic Reviews（系统综述） 6 Safety and efficacy of gepotidacin in urinary tract infection: a GRADE-assessed systematic review and meta-analysis 吉泊替达辛治疗尿路感染的安全性和有效性：一项基于GRADE评估的系统综述和荟萃分析 Taha Ibrahim and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf469, https://doi.org/10.1093/jac/dkaf469 7 The emerging clinical relevance and antimicrobial resistance of Pluralibacter gergoviae: a systematic review 产吲哚金黄杆菌日益凸显的临床相关性和抗菌药物耐药性：一项系统综述 Bruna Abdul Ahad Saad and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf476, https://doi.org/10.1093/jac/dkaf476 8 A comprehensive analysis of the mutational landscape determining polymyxin resistance in Klebsiella pneumoniae 决定肺炎克雷伯菌多粘菌素耐药性的突变谱综合分析 Sambit Kumar Dwibedy and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf503, https://doi.org/10.1093/jac/dkaf503 9 Factors promoting or hindering self-administered outpatient parenteral antimicrobial therapy: a systematic literature review 促进或阻碍自我给药门诊静脉注射抗菌药物治疗的因素：一项系统文献综述 Hester H Stoorvogel and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf490, https://doi.org/10.1093/jac/dkaf490 Original Research（论著） 10 Cefepime/enmetazobactam for Gram-negative periprosthetic joint infections? A randomized porcine study on target tissue pharmacokinetics 头孢吡肟/恩美唑巴坦治疗革兰氏阴性假体周围关节感染？一项关于猪的靶组织药代动力学的随机研究 M B D Nielsen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf487, https://doi.org/10.1093/jac/dkaf487 11 Impact of extracorporeal membrane oxygenation modes on voriconazole exposure in critically ill patients 体外膜肺氧合模式对危重患者伏立康唑暴露的影响 Xinrui Wang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf501, https://doi.org/10.1093/jac/dkaf501 12 Model-based assessment of VRC07-523LS dosing in infants through population pharmacokinetic -pharmacodynamic modelling in adults and infants 基于模型通过成人和婴儿群体药代动力学-药效学模型评估VRC07-523LS在婴儿中的给药方案 Dustin Huynh and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf449, https://doi.org/10.1093/jac/dkaf449 13 Antibiotic resistance of Pseudomonas aeruginosa strains—intracellular metabolomics analysis 铜绿假单胞菌菌株的抗生素耐药性——细胞内代谢组学分析 Karolina Anna Mielko-Niziałek and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf453, https://doi.org/10.1093/jac/dkaf453 14 In vitro activity of cefepime/zidebactam against sulbactam/durlobactam-susceptible and -resistant Acinetobacter baumannii clinical isolates 头孢吡肟/齐多巴坦对舒巴坦/杜洛巴坦敏感和耐药鲍曼不动杆菌临床分离株的体外活性 Carlo Tascini and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf467, https://doi.org/10.1093/jac/dkaf467 15 Prevalence of macrolide resistance in Mycoplasma pneumoniae in The Netherlands 荷兰肺炎支原体大环内酯类抗生素耐药性的流行情况 Patrick D J Sturm and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf475, https://doi.org/10.1093/jac/dkaf475 16 Simulated lung exposure in pneumonia patients to evaluate the antibacterial capacity and resistance suppression of clinical tigecycline regimens against carbapenem-resistant Acinetobacter baumannii 模拟肺炎患者肺部暴露情况以评估临床替加环素方案对碳青霉烯类耐药鲍曼不动杆菌的抗菌能力和耐药抑制作用 Xiaonan Zhang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf477, https://doi.org/10.1093/jac/dkaf477 17 Enterococcus faecium harbouring vanA, optrA and cfr(D) on a linear plasmid in Canada: a CANWARD surveillance case 加拿大发现携带vanA、optrA和cfr(D)的粪肠球菌线性质粒：一项CANWARD监测病例 Melissa McCracken and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf478, https://doi.org/10.1093/jac/dkaf478 18 The effect of intrauterine exposure to aminoglycosides on neonatal hearing 宫内暴露于氨基糖苷类抗生素对新生儿听力的影响 Daniel Leshin-Carmel and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf483, https://doi.org/10.1093/jac/dkaf483 19 Ceftazidime/avibactam: a potent arsenal against multidrug-resistant Pseudomonas aeruginosa-unveiling in vitro and in vivo strategies 头孢他啶/阿维巴坦：对抗多重耐药铜绿假单胞菌的有力武器——揭示体内外策略 Jiaju Zhuo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf495, https://doi.org/10.1093/jac/dkaf495 20 Comparison of disk diffusion, MIC test strip and broth microdilution for eravacycline susceptibility testing of 422 Staphylococcus aureus isolates using ChinaCAST breakpoints 采用中国CAST折点，比较422株金黄色葡萄球菌对依拉环素的纸片扩散法、最低抑菌浓度测试条法和肉汤微量稀释法的敏感性测试结果 Xinying Wang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf502, https://doi.org/10.1093/jac/dkaf502 21 Penetration of daptomycin in cerebrospinal fluid during pneumococcal meningitis 肺炎链球菌性脑膜炎期间达托霉素在脑脊液中的渗透情况 Pascal Chavanet and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf474, https://doi.org/10.1093/jac/dkaf474 22 Rapid molecular diagnostics for detection of extensively drug-resistant Salmonella Typhi 用于检测广泛耐药伤寒沙门菌的快速分子诊断技术 Emma L Sweeney and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf481, https://doi.org/10.1093/jac/dkaf481 23 Gender inequality and antibiotic consumption: analysis of pharmaceutical sales data from 70 countries, 2000–22 性别不平等与抗生素消费：基于2000 - 2022年70个国家药品销售数据的分析 Deepshikha Batheja and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag002, https://doi.org/10.1093/jac/dkag002 24 Real-world evaluation of isavuconazole in children with cancer 伊沙康唑在儿童癌症患者中的现实应用评估 Janine Nijhuis and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf485, https://doi.org/10.1093/jac/dkaf485 25 Assessing antimicrobial susceptibility testing guideline adherence by laboratories providing bacteriology services in Ghana: a pilot study 加纳提供细菌学服务的实验室对抗菌药物敏感性试验指南依从性的评估：一项试点研究 Joseph Elikem Efui Acolatse and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag003, https://doi.org/10.1093/jac/dkag003 26 Resistance to second-generation integrase inhibitors in people with HIV following treatment failure on dolutegravir- or bictegravir-based ART in Taiwan 台湾地区基于多替拉韦或比克替拉韦的抗逆转录病毒治疗失败后，HIV感染者对第二代整合酶抑制剂的耐药性 Guan-Jhou Chen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf488, https://doi.org/10.1093/jac/dkaf488 27 In vitro activity of gepotidacin against a challenging panel of multidrug-resistant Neisseria gonorrhoeae isolates 吉泊西汀对一组具有挑战性的多重耐药淋病奈瑟菌分离株的体外活性 Michelle Jayne Cole and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag001, https://doi.org/10.1093/jac/dkag001 28 A disproportionality analysis of adverse events associated with omadacycline based on the FDA adverse event reporting system database 基于美国食品药品监督管理局（FDA）不良事件报告系统数据库的奥马环素相关不良事件比例失衡分析 Ye-Lei Zhao and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag006, https://doi.org/10.1093/jac/dkag006 29 Weight-band-based simplification of oral allometric miltefosine dosing in paediatric patients with visceral leishmaniasis 基于体重范围的口服异速缩放米替福新给药方案在儿童内脏利什曼病患者中的简化应用 Andres Mazariegos Herrera and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag014, https://doi.org/10.1093/jac/dkag014 30 evelopment of a capability framework for antimicrobial stewardship specialist health professionals working in the NHS in England: utilizing Delphi methodology 运用德尔菲法为在英国国家医疗服务体系（NHS）中工作的抗菌药物管理专业人员制定能力框架 Ryan A Hamilton and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf438, https://doi.org/10.1093/jac/dkaf438 31 First characterization of insertions in the HIV-1 integrase-coding region from people with HIV 首次对来自艾滋病病毒感染者的HIV-1整合酶编码区插入情况进行特征分析 Nhat Quang Tu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf491, https://doi.org/10.1093/jac/dkaf491 32 Development of an impedance-based fast antimicrobial susceptibility test for Neisseria gonorrhoeae 开发一种基于阻抗的淋病奈瑟菌快速抗菌药物敏感性检测方法 Caitlin N Daniels and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf493, https://doi.org/10.1093/jac/dkaf493 33 Juvenile toxicity and developmental safety of Zintrodiazine, a novel antimalarial candidate, in Wistar rats 新型抗疟候选药物Zintrodiazine在Wistar大鼠中的幼年毒性和发育安全性研究 Hitesh A Kadu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag008, https://doi.org/10.1093/jac/dkag008 34 Do the redefined EUCAST susceptibility categories warrant adjustment of paediatric antibiotic dosages? Pragmatic physiologically based pharmacokinetic modelling of four commonly used agents 欧洲抗微生物药物敏感性试验委员会（EUCAST）重新定义的敏感性分类是否需要调整儿童抗生素剂量？——对四种常用药物的实用生理药代动力学建模研究 Marika A de Hoop-Sommen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf463, https://doi.org/10.1093/jac/dkaf463 35 Exploring the opportunity for therapeutic drug monitoring (TDM) and precision dose antimicrobials in an outpatient antimicrobial therapy (OPAT) service: a prospective observational study 门诊抗菌治疗（OPAT）服务中开展治疗药物监测（TDM）和精准剂量抗菌治疗的机遇：一项前瞻性观察研究 R C Wilson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf484, https://doi.org/10.1093/jac/dkaf484 36 Impact of sex, age and body composition on rilpivirine and cabotegravir trough concentrations in people with HIV receiving long-acting injectable antiretroviral therapy 性别、年龄和身体成分对接受长效注射用抗逆转录病毒治疗的HIV感染者利匹韦林和卡博特韦谷浓度的影响 Maria Vittoria Cossu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag024, https://doi.org/10.1093/jac/dkag024 37 Pharmacokinetics of cefiderocol during prolonged intermittent kidney replacement therapy in two patients with septic shock 头孢地尔在两例感染性休克患者长时间间歇性肾脏替代治疗期间的药代动力学 Julius J Schmidt and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf496, https://doi.org/10.1093/jac/dkaf496 38 Understanding mechanisms of reduced cefiderocol susceptibility in pvdS and fecI mutants of Pseudomonas aeruginosa 了解铜绿假单胞菌pvdS和fecI突变体对头孢地尔敏感性降低的机制 Yoshinori Yamano and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag004, https://doi.org/10.1093/jac/dkag004 39 Biomarker-informed PBPK modelling of meropenem in paediatric severe pneumonia: implications for target-site PK/PD 基于生物标志物的美罗培南在儿童重症肺炎中的生理药动学模型构建：对靶部位药代动力学/药效学的影响 Yao Liu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf500, https://doi.org/10.1093/jac/dkaf500 40 Evaluating hypoalbuminaemia thresholds associated with delayed blood sterilization among patients receiving cefazolin or antistaphylococcal penicillins for MSSA bacteraemia 评估接受头孢唑林或抗葡萄球菌青霉素治疗甲氧西林敏感金黄色葡萄球菌（MSSA）菌血症患者中，与血液延迟灭菌相关的低白蛋白血症阈值 Sunish Shah and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf498, https://doi.org/10.1093/jac/dkaf498 Research Letters（研究快讯） 41 False-negative result in fourth-generation HIV screening tests after weak detection of p24 antigen in the context of inappropriate post-exposure prophylaxis use: a case report 不当使用暴露后预防用药导致第四代HIV筛查试验p24抗原弱检出后出现假阴性结果：一例病例报告 J Kimmerlin and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf459, https://doi.org/10.1093/jac/dkaf459 42 Proposal for the nomenclature of tmexCD-toprJ-like gene clusters 关于tmexCD-toprJ样基因簇命名的建议 Chengzhen Wang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf482, https://doi.org/10.1093/jac/dkaf482 43 IS26-mediated chromosomal integration of virulence plasmid fragments in ST2237 carbapenem-resistant Klebsiella pneumoniae IS26介导的毒力质粒片段在ST2237型碳青霉烯耐药肺炎克雷伯菌染色体中的整合 Yan Li and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag018, https://doi.org/10.1093/jac/dkag018 Letter to the Editor（致编辑的信） 44 Comment on: Retrospective analysis of pharmacological therapeutic monitoring of caspofungin in patients undergoing continuous renal replacement therapy using polyacrylonitrile membranes 对“采用聚丙烯腈膜对接受连续性肾脏替代治疗的患者进行卡泊芬净药代动力学监测的回顾性分析”的评论 Gwénola Marais and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf465, https://doi.org/10.1093/jac/dkaf465 45 Antimicrobial use for the treatment of bacterial sexually transmitted infections among doxycycline post-exposure prophylaxis (DoxyPEP) users in Milan, Italy-right-to-reply 意大利米兰地区使用多西环素暴露后预防（DoxyPEP）人群中，用于治疗细菌性传播感染的抗菌药物使用情况——回应说明 Angelo Roberto Raccagni and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag027, https://doi.org/10.1093/jac/dkag027 ACKNOWLEDGEMENT OF REFEREES（鸣谢审稿专家） 46 Acknowledgement of Referees 鸣谢审稿专家 Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf417, https://doi.org/10.1093/jac/dkaf417 CORRECTION（更正） 47 Correction to: Comment on: Antiviral effect of Evusheld in COVID-19 hospitalized patients infected with pre-Omicron or Omicron variants: a modelling analysis of the randomized DisCoVeRy trial 更正：关于Evusheld在感染奥密克戎变异株前或奥密克戎变异株的新冠住院患者中的抗病毒效果：对随机DisCoVeRy试验的建模分析的评论 Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf492, https://doi.org/10.1093/jac/dkaf492 Journal of Antimicrobial Chemotherapy Volume 81, Issue 3抗菌化疗杂志 81卷 3期 https://academic.oup.com/jac/issue REVIEW（综述） 1 Closing the PrEP access gap in Europe: a strategic framework for equity and innovation among difficult-to-reach populations 缩小欧洲暴露前预防获取差距：面向难以触及（PrEP）人群的公平与创新战略框架 Josep M Llibre and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag052, https://doi.org/10.1093/jac/dkag052 2 Precision dosing of systemic antifungals in adults: therapeutic drug monitoring, empiric dose optimization and barriers to implementation 成人全身性抗真菌药物的精准给药：治疗药物监测、经验性剂量优化及实施障碍 Daniel B Chastain and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag055, https://doi.org/10.1093/jac/dkag055 3 Bacterial DNA topoisomerase IV and DNA gyrase inhibitors: history of the quinolones, their clinical usage and potential alternatives for the future 细菌DNA拓扑异构酶IV和DNA旋转酶抑制剂：喹诺酮类药物的历史、临床应用及未来潜在替代方案 Daisuke Fukuda and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag054, https://doi.org/10.1093/jac/dkag054 4 Combating multidrug-resistant Klebsiella pneumoniae: current therapeutic regimens and future directions 应对多重耐药肺炎克雷伯菌：当前治疗方案与未来方向 Robiul Islam and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag064, https://doi.org/10.1093/jac/dkag064 SYSTEMATIC REVIEW（系统综述） 5 Global and regional prevalence of metallo-β-lactamases in carbapenem-resistant Acinetobacter baumannii: a systematic review and meta-analysis 耐碳青霉烯类鲍曼不动杆菌中金属β-内酰胺酶的全球和区域流行情况：一项系统综述和荟萃分析 Stamatis Karakonstantis and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag037, https://doi.org/10.1093/jac/dkag037 Original Research（论著） 6 The effect of oral ciprofloxacin at conventional doses on the QT interval in a tertiary outpatient setting 三级门诊常规剂量口服环丙沙星对患者QT间期的影响 Weber Liu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag020, https://doi.org/10.1093/jac/dkag020 7 Bictegravir concentrations in breastmilk of healthy, lactating women without HIV 未感染人类免疫缺陷病毒（HIV）的健康哺乳期女性乳汁中的比克替拉韦浓度 L C van der Wekken-Pas and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag022, https://doi.org/10.1093/jac/dkag022 8 Management and outcomes of Stenotrophomonas maltophilia recovered from deep-site clinical specimens: a bicentric retrospective cohort study 从深部部位临床标本中分离出的嗜麦芽窄食单胞菌的治疗及转归：一项双中心回顾性队列研究 Anastasia Saade and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag021, https://doi.org/10.1093/jac/dkag021 9 Development of a risk prediction model for vancomycin-associated acute kidney injury: a multicentre retrospective study 万古霉素相关急性肾损伤风险预测模型的建立：一项多中心回顾性研究 Tomoyuki Ishigo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag012, https://doi.org/10.1093/jac/dkag012 10 Cooperation between HIV-1 integrase natural polymorphism K156N and 3′PPT mutations in dolutegravir monotherapy failure HIV-1 整合酶天然多态性 K156N 与 3′PPT 突变在多替拉韦单药治疗失败中的协同作用 Jolieke A T van Osch and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag033, https://doi.org/10.1093/jac/dkag033 11 Impact of body mass index and serum albumin levels on isavuconazole plasma concentrations in patients with haematological malignancies 体重指数和血清白蛋白水平对血液系统恶性肿瘤患者艾沙康唑血浆浓度的影响 Jie Gao and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag032, https://doi.org/10.1093/jac/dkag032 12 Pharmacokinetics of cefotaxime and its metabolite desacetyl-cefotaxime to optimize dosing in critically ill children and children with sickle cell disease 用以优化危重症儿童和镰状细胞病儿童给药剂量的头孢噻肟及其代谢产物去乙酰头孢噻肟的药代动力学研究 Seef Abdalla and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag019, https://doi.org/10.1093/jac/dkag019 13 Summary of ceftriaxone-resistant Neisseria gonorrhoeae in Canada, 2017–24 2017 - 2024年加拿大头孢曲松耐药淋病奈瑟菌情况汇总 Robyn Thorington and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag007, https://doi.org/10.1093/jac/dkag007 14 Improving perioperative prophylactic antibiotic prescribing using a novel decision-support tool 使用新型决策支持工具改进围手术期预防性抗生素处方 Mark Mcintyre and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag015, https://doi.org/10.1093/jac/dkag015 15 Comparative activity of established versus new-generation β-lactams against AmpC-hyperproducing clinical isolates of Enterobacter cloacae complex and Klebsiella aerogenes: a multicentre study 针对产超广谱AmpC酶的阴沟肠杆菌复合群和产气克雷伯菌临床分离株，比较已上市与新一代β-内酰胺类抗生素的抗菌活性：一项多中心研究 Ángel Rodríguez-Villodres and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag034, https://doi.org/10.1093/jac/dkag034 16 Impact of eravacycline on fibrinogen 依拉环素对纤维蛋白原的影响 Emily Stevenson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag030, https://doi.org/10.1093/jac/dkag030 17 Biliary pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime–avibactam in a case series of orthotopic liver transplant recipients 原位肝移植受者连续输注头孢他啶-阿维巴坦的药代动力学/药效学胆系分析：一项病例系列研究 Milo Gatti and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag009, https://doi.org/10.1093/jac/dkag009 18 Autoaggregation-associated carbapenem tolerance mediated by mrkH inactivation identified from a cohort of Klebsiella pneumoniae species complex clinical isolates 从肺炎克雷伯菌复合群临床分离株队列中鉴定出由mrkH失活介导的与自动聚集相关的碳青霉烯耐受性 Natsuki Yamanaka and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag017, https://doi.org/10.1093/jac/dkag017 19 In vitro activity of double and triple antimicrobial combinations against carbapenem-resistant Pseudomonas aeruginosa biofilm 双联和三联抗菌药物组合对碳青霉烯耐药铜绿假单胞菌生物膜的体外活性研究 Si-Ho Kim and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag031, https://doi.org/10.1093/jac/dkag031 20 LYSC98 as a novel vancomycin-derived agent effective against antibiotic-resistant pathogens in tolerant state LYSC98作为一种新型万古霉素衍生物，对耐受状态下的耐药病原体有效 Xing Xia and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag036, https://doi.org/10.1093/jac/dkag036 21 HBV status modulates transaminase decrease after switching from tenofovir disoproxil fumarate to tenofovir alafenamide in people with HIV HIV感染者从富马酸替诺福韦二吡呋酯切换为丙酚替诺福韦后，HBV状态对转氨酶下降的调节作用 Giuseppe Lapadula and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag045, https://doi.org/10.1093/jac/dkag045 22 Pharmacokinetics of colistin in adult critically ill patients in South Africa 南非成人危重症患者中多黏菌素的药代动力学研究 Veshni Pillay-Fuentes Lorente and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag011, https://doi.org/10.1093/jac/dkag011 23 Antifungal susceptibility surveillance of clinical moulds to olorofim, manogepix, amphotericin B, triazoles and echinocandins at 10 tertiary hospitals in China (2019–24) 2019 - 2024年中国10家三级医院临床霉菌对奥罗芬净、马诺盖匹克斯、两性霉素B、三唑类和棘白菌素类抗真菌药的敏感性监测 Su Chen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag016, https://doi.org/10.1093/jac/dkag016 24 Short-cycle three-day-per-week efavirenz/emtricitabine/tenofovir disoproxil fumarate therapy: a seven-year extension study 短周期每周三日依非韦伦/恩曲他滨/富马酸替诺福韦二吡呋酯疗法：一项为期七年的延长研究 Beatriz Borjabad and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag040, https://doi.org/10.1093/jac/dkag040 25 Risk of hypertension in people with HIV in the USA initiating modern antiretroviral regimens: pooled analysis of blood pressure data from five clinical trials 美国感染HIV者启动现代抗逆转录病毒治疗方案后患高血压的风险：五项临床试验血压数据汇总分析 Priscilla Y Hsue and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag005, https://doi.org/10.1093/jac/dkag005 26 Real-world drug monitoring of dalbavancin using a three-dose regimen of 1500mg at days 1, 15 and 43 in bone and joint or cardiovascular infection 采用第1、15和43天各1500毫克的三剂量方案对达巴万星（Dalbavancin）在骨关节或心血管感染治疗中的实际药物监测研究 Thomas Lin and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag039, https://doi.org/10.1093/jac/dkag039 27 Nationwide patterns of HIV drug resistance and high viral load in Sub-Saharan African countries 撒哈拉以南非洲国家全国范围内的HIV耐药及高病毒载量模式 Abubaker Ibrahim Elbur and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkaf497, https://doi.org/10.1093/jac/dkaf497 28 Risk factors for suboptimal target attainment of commonly used ß-lactam antibiotics in older adults: a prospective cohort study 老年人常用β-内酰胺类抗生素未达最佳治疗目标的风险因素：一项前瞻性队列研究 Arnaud De Clercq and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag048, https://doi.org/10.1093/jac/dkag048 29 Physiologically based pharmacokinetic modelling to optimize dosing regimen of biapenem in renal impairment and elderly populations 基于生理的药代动力学模型优化肾功能不全及老年人群比阿培南给药方案 Wenyan Li and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkaf499, https://doi.org/10.1093/jac/dkaf499 30 Early targeted therapy guided by rapid phenotypic antimicrobial susceptibility testing in critically ill patients with Gram-negative bacterial bloodstream infections: a retrospective cohort study 快速表型抗菌药物敏感性试验指导下的早期目标性治疗对革兰氏阴性菌血流感染危重患者的效果：一项回顾性队列研究 Salvatore Rotundo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag056, https://doi.org/10.1093/jac/dkag056 31 Impact of COVID-19-related healthcare changes on antibiotic resistance in clinical Escherichia coli isolates: interrupted time series analyses in Scotland, UK 与新冠肺炎相关的医疗变化对英国苏格兰地区临床大肠杆菌分离株抗生素耐药性的影响：中断时间序列分析 Laura Ciaccio and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag049, https://doi.org/10.1093/jac/dkag049 32 Multicentre evaluation of teicoplanin prescribing and monitoring in the UK and Ireland: the TUcK–SHOP study 英国和爱尔兰替考拉宁处方与监测的多中心评估：TUcK–SHOP研究 Stephen Hughes and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag038, https://doi.org/10.1093/jac/dkag038 33 Diabetes and risk of significant fibrosis in adults with HIV and metabolic dysfunction-associated steatotic liver disease: a prospective cohort study 糖尿病与HIV合并代谢功能障碍相关脂肪性肝病成人患者发生显著肝纤维化的风险：一项前瞻性队列研究 Win Min Han and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag053, https://doi.org/10.1093/jac/dkag053 34 A pharmacovigilance analysis of carbapenem-related utilizing the FDA adverse event reporting system (FAERS) database from 2013 to 2025 基于美国食品药品监督管理局不良事件报告系统（FAERS）数据库2013 - 2025年数据的碳青霉烯类相关药物警戒分析 Connor Frey and Parham Elmi Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag060, https://doi.org/10.1093/jac/dkag060 35 Effects of extracorporeal membrane oxygenation on the pharmacokinetics and tissue penetration rates of vancomycin and linezolid: data from Landrace pigs 体外膜肺氧合对万古霉素和利奈唑胺药代动力学及组织穿透率的影响：来自长白猪的数据 Huifang Zhang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag063, https://doi.org/10.1093/jac/dkag063 36 Switching to bictegravir/emtricitabine/tenofovir alafenamide in people with HIV and prior resistance mutations. Data from the Italian ARCA cohort: the BIC-BARRIER study. B/F/TAF switch: mutations and outcomes 在既往存在耐药突变的人类免疫缺陷病毒（HIV）感染者中换用比克替拉韦/恩曲他滨/丙酚替诺福韦治疗。来自意大利ARCA队列的数据：BIC-BARRIER研究。比克替拉韦/恩曲他滨/丙酚替诺福韦（B/F/TAF）换药方案：耐药突变与治疗结果 Laura Pezzati and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag035, https://doi.org/10.1093/jac/dkag035 37 A two-stage diagnostic model for discriminating and assessing risk of meropenem heteroresistance in Pseudomonas aeruginosa 用于鉴别和评估铜绿假单胞菌对美罗培南异质性耐药风险的二阶段诊断模型 Yali Fan and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag061, https://doi.org/10.1093/jac/dkag061 38 Microdialysis assessment of gentamicin for second-line antimicrobial prophylaxis in abdominal surgery 微透析评估庆大霉素在腹部手术中作为二线抗菌预防药物的效果 Quentin Saint-Genis and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag071, https://doi.org/10.1093/jac/dkag071 39 Genetic and clinical predictors of voriconazole pharmacokinetics and hepatotoxicity: focused on CYP2C19 normal and intermediate metabolizers 伏立康唑药代动力学及肝毒性的遗传和临床预测因素：聚焦于CYP2C19正常代谢型和中间代谢型 Hui Li and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag065, https://doi.org/10.1093/jac/dkag065 40 Stakeholder perspectives on the offer and acceptance of self-administration of outpatient parenteral antimicrobial therapy: a qualitative study 利益相关者对提供和接受门诊患者自行注射抗菌药物治疗的看法：一项定性研究 Hester H Stoorvogel and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag068, https://doi.org/10.1093/jac/dkag068 41 Is current guidance for cloxacillin prophylaxis dosages in hip and knee arthroplasty adequate? Evidence from a prospective Swedish cohort 当前髋关节和膝关节置换术中氯唑西林预防性用药剂量指南是否充分？来自一项前瞻性瑞典队列研究的证据 Katja Wallander and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag067, https://doi.org/10.1093/jac/dkag067 42 Effect of pretreatment HIV drug resistance on mortality, attrition and viral suppression in patients initiating antiretroviral therapy and genetic transmission network: an observational cohort study in Southwest China 治疗前HIV药物耐药性对开始接受抗逆转录病毒治疗患者的死亡率、失访率和病毒抑制率的影响以及遗传传播网络：中国西南地区一项观察性队列研究 Litai Qin and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag073, https://doi.org/10.1093/jac/dkag073 RESEARCH LETTER（研究快讯） 43 Varicella and varicella zoster virus meningoencephalitis in a diffuse large B-cell lymphoma patient after chimeric antigen receptor-T-cell therapy 嵌合抗原受体T细胞疗法后，弥漫性大B细胞淋巴瘤患者发生水痘及水痘-带状疱疹病毒脑膜脑炎 Yan Feng and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag041, https://doi.org/10.1093/jac/dkag041 44 The ‘double hit’ on dalbavancin pharmacokinetics: hypertriglyceridaemia and augmented renal clearance in a child with glycogen storage disease type Ib 糖原累积病Ib型患儿中，高甘油三酯血症和肾清除率增加对达巴万星药代动力学的“双重打击” Bianca Monti and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag028, https://doi.org/10.1093/jac/dkag028 45 Tn7860, a novel chromosomal pseudo-compound transposon carrying the OptrA gene in Enterococcus faecalis Tn7860，粪肠球菌中携带OptrA基因的一种新型染色体假复合转座子 Francesca Romana Massacci and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag046, https://doi.org/10.1093/jac/dkag046 46 HBV reactivation after switching to cabotegravir plus rilpivirine therapy among people living with HIV: do not forget the reservoir HIV感染者换用卡博特韦（cabotegravir）联合利匹韦林（rilpivirine）治疗后乙肝病毒再激活：切勿忽视病毒储存库 Rémi Rouget and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag050, https://doi.org/10.1093/jac/dkag050 47 An inoperable mediastinal infection involving vascular graft treated with weekly oritavancin as chronic suppressive therapy. A case report with pharmacokinetic data 一例涉及血管移植物的无法手术的纵隔感染，采用每周一次的奥利万星作为慢性抑制疗法。附药代动力学数据的病例报告 Pierangelo Chinello and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag013, https://doi.org/10.1093/jac/dkag013 48 Evaluation of the Carbapenemase Detection Kit (Colloidal Gold; Macro & Micro Test): a new immunochromatographic assay for rapid detection of carbapenemases in Enterobacterales 碳青霉烯酶检测试剂盒（胶体金法；宏基因与微基因检测法）评估：一种用于快速检测肠杆菌目细菌中碳青霉烯酶的新型免疫层析法 Hippolyte De Swardt and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag066, https://doi.org/10.1093/jac/dkag066 49 Cefalexin use in UK acute pyelonephritis practice: unaddressed challenges in dosing, breakpoints and clinical evidence 头孢氨苄在英国急性肾盂肾炎治疗中的应用：给药、断点和临床证据方面尚未解决的挑战 Stephen Hughes and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag051, https://doi.org/10.1093/jac/dkag051 LETTERS TO THE EDITOR（致编辑的信） 50 Comment on: Antimicrobial use for the treatment of bacterial sexually transmitted infections among doxycycline post-exposure prophylaxis (DoxyPEP) users in Milan, Italy 评论：意大利米兰多西环素暴露后预防（DoxyPEP）使用者中用于治疗细菌性性传播感染的抗菌药物使用情况 Chris Kenyon Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag025, https://doi.org/10.1093/jac/dkag025 51 Possible increased risk of Epstein–Barr virus (EBV) infection and post-transplant lymphoproliferative disease (PTLD) in letermovir-exposed haematopoietic cell transplantation recipients: right-to-reply 来特莫韦暴露的造血细胞移植受者发生EB病毒（EBV）感染和移植后淋巴增殖性疾病（PTLD）的风险可能增加：答复权 Jose F Camargo and Anthony D Anderson Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag043, https://doi.org/10.1093/jac/dkag043 52 Antimicrobial use for the treatment of bacterial sexually transmitted infections among doxycycline post-exposure prophylaxis (DoxyPEP) users in Milan, Italy—right-to-reply 意大利米兰市使用多西环素暴露后预防（DoxyPEP）人群中，用于治疗细菌性性传播感染的抗菌药物使用情况——答复权声明 Angelo Roberto Raccagni and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag026, https://doi.org/10.1093/jac/dkag026 53 Comment on: Artificial intelligence for improving decision-making in bacterial infection management 述评：人工智能在细菌感染管理决策中的优化作用 Daniele Roberto Giacobbe Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag078, https://doi.org/10.1093/jac/dkag078 CORRECTION（更正） 54 Correction to: Bayesian estimation of the prevalence of antimicrobial resistance: a mathematical modelling study 更正：抗菌药物耐药性流行率的贝叶斯估计：一项数学建模研究 Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkaf494, https://doi.org/10.1093/jac/dkaf494 55 Correction to: National representative survey of pretreatment HIV drug resistance in Colombia: analysis of antiretroviral resistance-associated mutations using next-generation sequencing 更正：哥伦比亚具有全国代表性的治疗前HIV耐药性调查：使用下一代测序技术分析抗逆转录病毒耐药相关突变 Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag057, https://doi.org/10.1093/jac/dkag057 Journal of Antimicrobial Chemotherapy Volume 81, Issue 4抗菌化疗杂志81卷 4期 https://academic.oup.com/jac/issue 50TH ANNIVERSARY COLLECTION（50周年纪念合集） GARROD LECTURE（加罗德讲座） 1 Garrod lecture: achieving the UNGA AMR mortality reduction goals 加罗德讲座：实现联合国大会抗菌药物耐药性死亡率降低目标 Ramanan Laxminarayan Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag082, https://doi.org/10.1093/jac/dkag082 REVIEW（综述） 2 25 years of improvement in mortality in invasive aspergillosis in haematology patients: will it be sustained or is it under threat? 侵袭性曲霉病血液病患者25年死亡率改善情况：这种改善能否持续，还是正受到威胁？ Johan A Maertens and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag077, https://doi.org/10.1093/jac/dkag077 3 A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 2: from molecule to confirmed hit 针对锥虫病的从高质量潜在客户和药物开发候选者出发的战略发现路线图。第二部分：从分子到确证活性分子 Sarah Hendrickx and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag110, https://doi.org/10.1093/jac/dkag110 VIRTUAL ROUNDTABLE（虚拟圆桌会议） 4 Diagnosis and risk factors for invasive mould disease—a round table discussion on directing antifungal therapy according to the available evidence 侵袭性霉菌病的诊断与危险因素——根据现有证据指导抗真菌治疗的圆桌讨论 Ana Alastruey-Izqueirdo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag062, https://doi.org/10.1093/jac/dkag062 EDITORIALS, MESSAGES FROM THE OUTGOING AND INCOMING EDITORS-IN-CHIEF（社论、离任与就任主编寄语） 5 Message from the incoming Editor-in-Chief of JAC 《抗菌化疗杂志》就任主编寄语 Monica A Slavin Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkaf479, https://doi.org/10.1093/jac/dkaf479 6 Message from the outgoing Editor-in-Chief 离任主编寄语 J Peter Donnelly Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkaf480, https://doi.org/10.1093/jac/dkaf480 REVIEW（综述） 7 Experimental biofilm models for pharmacokinetic and pharmacodynamic investigations: bridging in vitro, ex vivo and in vivo systems 用于药代动力学和药效学研究的实验性生物膜模型：连接体外、离体和体内系统 Stephanie Supparitsch and Markus Zeitlinger Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag091, https://doi.org/10.1093/jac/dkag091 8 Antimicrobial therapy for infected necrotizing pancreatitis: microbiology, antimicrobial resistance and pharmacokinetics 感染性坏死性胰腺炎的抗菌治疗：微生物学、抗菌药物耐药性及药代动力学 Hannah S Pauw and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag092, https://doi.org/10.1093/jac/dkag092 9 Continuous linezolid infusion: the new way to dose, the old risks to fear 持续输注利奈唑胺：新的给药方式，仍需警惕旧有风险 Daniel Muñoz-Pichuante and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag100, https://doi.org/10.1093/jac/dkag100 10 Alignment of national standard treatment guidelines with WHO AWaRe recommendations for adult primary care infectious diseases: implications for antimicrobial stewardship 将国家标准治疗指南与世卫组织（WHO）针对成人初级保健传染病的“慎用、监测、备用”（AWaRe）推荐意见相统一：对抗菌药物管理的影响 Huda Arooj and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag099, https://doi.org/10.1093/jac/dkag099 SYSTEMATIC REVIEW（系统综述） 11 Healthcare providers’ experiences in caring for MDRO carriers with a focus on the moral dimensions of care: a systematic review 医疗服务提供者护理多重耐药菌（MDRO）携带者的经历——聚焦护理中的道德维度：一项系统综述 Carlijn Damsté and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag059, https://doi.org/10.1093/jac/dkag059 12 Extrapolation of oritavancin PK/PD targets to inform therapeutic drug monitoring: a systematic review 奥利他万星药代动力学/药效学目标的外推用以指导治疗药物监测：一项系统综述 Giammarco Baiardi and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag117, https://doi.org/10.1093/jac/dkag117 ORIGINAL RESEARCH（论著） 13 Beyond plasma: defining the translation value of epithelial lining fluid exposure profiles for the treatment of pneumonia 超越血浆：明确上皮衬里液暴露谱对肺炎治疗的转化价值 Yakun Fu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkaf458, https://doi.org/10.1093/jac/dkaf458 14 Impact of loading dose β-lactam therapy on outcomes of KPC-producing Klebsiella pneumoniae bloodstream infections in non-ICU patients: a real world study 负荷剂量β-内酰胺类药物治疗非重症监护病房患者产KPC肺炎克雷伯菌血流感染的疗效影响：一项现实研究 Luisa Frallonardo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag087, https://doi.org/10.1093/jac/dkag087 15 Rezafungin exhibits anti-biofilm properties against fungal biofilms in vitro 雷扎芬净在体外对真菌生物膜表现出抗生物膜特性 Hafsa Abduljalil and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag058, https://doi.org/10.1093/jac/dkag058 16 Vancomycin resistance predicts increased mortality in patients with Enterococcus faecium bloodstream infections: a six-year experience at a large tertiary care Italian hospital 万古霉素耐药性可预测屎肠球菌血流感染患者死亡率增加：意大利一家大型三级医院六年来的经验 Lucia Graziani and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag069, https://doi.org/10.1093/jac/dkag069 17 Fluoroquinolones and the risk of panic attacks: a systematic review and disproportionality analysis using individual case safety reports from the FDA Adverse Event Reporting System (FAERS) database 氟喹诺酮类药物与惊恐发作风险：基于美国食品药品监督管理局不良事件报告系统（FAERS）数据库中个体病例安全报告的系统综述和比例失衡分析 Keeirah Hiertika Raguram and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag083, https://doi.org/10.1093/jac/dkag083 18 Cefuroxime concentrations in facial artery musculomucosal flap, buccal submucosa, subcutaneous tissue, and plasma following bolus or continuous infusion in patients undergoing oral cancer resection: a randomized clinical microdialysis study 在接受口腔癌切除术的患者中，采用随机临床微透析研究，探究头孢呋辛在面动脉肌黏膜瓣、颊黏膜下层、皮下组织和血浆中的浓度（团注或持续输注后） Johanne Ravn Hansen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag085, https://doi.org/10.1093/jac/dkag085 19 Infection point of care tests bridge the experience gap of antibiotic STOP decisions: clinicians versus students 感染即时检测可弥补抗生素停药决策方面的经验差距：临床医生与学生对比 Archit Singhal and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkaf486, https://doi.org/10.1093/jac/dkaf486 20 Functional analysis of a novel macrolide–lincosamide resistance gene erm(57) in Cutibacterium avidum 痤疮丙酸杆菌中一种新型大环内酯 - 林可酰胺类耐药基因erm(57)的功能分析 Juri Koizumi and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag029, https://doi.org/10.1093/jac/dkag029 21 HIV drug resistance amongst children and adolescents with viraemia in Lesotho and Tanzania: a nested analysis in the GIVE MOVE trial 莱索托和坦桑尼亚病毒血症儿童及青少年中的HIV耐药性：GIVE MOVE试验的嵌套分析 Christof Manuel Schönenberger and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag070, https://doi.org/10.1093/jac/dkag070 22 Identification and assessment of paediatric cefepime-induced neurotoxicity in a retrospective cohort of paediatric intensive care patients 在儿科重症监护患者回顾性队列中识别和评估儿科头孢吡肟诱导的神经毒性 Kathryn Pavia and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag075, https://doi.org/10.1093/jac/dkag075 23 Prioritization of adverse events related to integrase inhibitors and NNRTIs: a disproportionality analysis using data from the FAERS database 整合酶抑制剂和非核苷类逆转录酶抑制剂相关不良事件的优先级排序：基于FAERS数据库数据的比例失衡分析 Gao-yang Wang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag074, https://doi.org/10.1093/jac/dkag074 24 Clinical and immunovirological status in children, adolescents and young adults with early-life-acquired HIV: a Spanish multi-cohort analysis since 2020 自2020年以来西班牙多队列分析中，儿童、青少年及青年时期感染HIV者的临床及免疫病毒学状态 Laura Tarancon-Diez and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag079, https://doi.org/10.1093/jac/dkag079 25 Population pharmacokinetics of meropenem in critically ill adult patients receiving extracorporeal membrane oxygenation—an ASAP ECMO study 接受体外膜肺氧合治疗的危重成年患者美罗培南的群体药代动力学——一项ASAP ECMO研究 Mohd H Abdul–Aziz and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag090, https://doi.org/10.1093/jac/dkag090 26 Evaluation of HIV-1 transmitted drug-resistance among subtypes circulating from 2022 to 2024 in Italy: a refined analysis through next-generation sequencing 2022年至2024年意大利流行HIV-1亚型间传播耐药性的评估：通过下一代测序技术进行的精细分析 Daniele Armenia and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag084, https://doi.org/10.1093/jac/dkag084 27 Characterization of efflux pump channel of florfenicol for resistance-enhancing variant RE-CmeABC in Campylobacter 耐药增强型变异体RE-CmeABC中氟苯尼考外排泵通道在弯曲菌中的特性研究 Hong Yao and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag047, https://doi.org/10.1093/jac/dkag047 28 Genomic characterization of colistin heteroresistance in Acinetobacter baumannii: Evidence for lpxD deletion and collateral sensitivity 鲍曼不动杆菌中黏菌素异质性耐药的基因组特征：lpxD缺失及附带敏感性的证据 Banu Sancak and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag076, https://doi.org/10.1093/jac/dkag076 29 Sustaining stewardship: longitudinal evaluation of an integrated antimicrobial programme in the ICU 持续管理：重症监护室（ICU）综合抗菌药物管理项目的纵向评估 Ashmitha Thomas and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag086, https://doi.org/10.1093/jac/dkag086 30 Global dissemination of optrA-mediated linezolid resistance in enterococci 利奈唑胺耐药性基因optrA介导的肠球菌在全球的传播 Jia Qi Beh and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag089, https://doi.org/10.1093/jac/dkag089 31 Predicting oral cephalosporin susceptibility in Escherichia coli blood isolates using parenteral cephalosporin susceptibility testing 利用肠外头孢菌素敏感性试验预测大肠杆菌血培养分离株对口服头孢菌素的敏感性 Tho H Pham and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag093, https://doi.org/10.1093/jac/dkag093 32 The pharmacodynamics of polymyxin B in Acinetobacter baumannii in murine thigh and lung infection models 在小鼠大腿和肺部感染模型中多粘菌素B对鲍曼不动杆菌的药效动力学研究 Sanne van den Berg and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag097, https://doi.org/10.1093/jac/dkag097 33 Genomic insights into the tmexCD-toprJ: plasmid-mediated evolution, dissemination and diversity in bacterial populations 关于tmexCD-toprJ的基因组见解：质粒介导的细菌群体进化、传播与多样性 Lilan Wan and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag107, https://doi.org/10.1093/jac/dkag107 34 Baseline resistance mutations and virological response to dolutegravir in treatment-naïve patients: a multicentre NGS study 初治患者基线耐药突变与多替拉韦病毒学应答：一项多中心下一代测序（NGS）研究 Alexy Inciarte and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag080, https://doi.org/10.1093/jac/dkag080 35 Novel integrase mutations linked to genotypic DTG resistance in African non-B HIV-1 strains: the DTG RESIST study 非洲非B型HIV-1毒株中与多替拉韦（DTG）基因型耐药相关的新型整合酶突变：DTG耐药研究 Nuri Han and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag088, https://doi.org/10.1093/jac/dkag088 36 Pharmacological evaluation of an ex vivo cervicovaginal HIV prevention model 体外宫颈阴道HIV预防模型的药理学评估 Lindsey B Collins and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag103, https://doi.org/10.1093/jac/dkag103 37 The magnitude of the pharmacodynamic index for NOSO-502: pathogen clearance, emergence of resistance and human dose predictions NOSO-502药效学指数的幅度：病原体清除、耐药性出现和人体剂量预测 Sanne van den Berg and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag106, https://doi.org/10.1093/jac/dkag106 38 Temocillin: a therapeutic alternative in bone and joint infections due to third generation cephalosporin-resistant Enterobacterales? 替莫西林：治疗第三代头孢菌素耐药肠杆菌目引起的骨关节感染的一种替代疗法？ Louise Piquart and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag105, https://doi.org/10.1093/jac/dkag105 39 Metallo-β-lactamase–producing Enterobacterales: cyanide-containing efflux pump inhibitors as potential dual-activity inhibitors 产金属β-内酰胺酶的肠杆菌科细菌：含氰化物的外排泵抑制剂作为潜在的双活性抑制剂 Otávio Hallal Ferreira Raro and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag122, https://doi.org/10.1093/jac/dkag122 40 Outer membrane vesicles transmit blaNDM-5 and package metallo-β-lactamases to promote antibiotic resistance in Escherichia coli 外膜囊泡传递blaNDM-5并包装金属β-内酰胺酶以促进大肠杆菌的抗生素耐药性 Ting-Yin Lu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag123, https://doi.org/10.1093/jac/dkag123 41 Characterization of a ST412-K57 colistin-resistant hypervirulent Klebsiella pneumoniae strain of chicken origin 一株鸡源ST412-K57多粘菌素耐药高毒力肺炎克雷伯菌的特征分析 Qiu Xu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag114, https://doi.org/10.1093/jac/dkag114 42 Olorofim in combination with azole antifungals: results from the Phase 2 salvage therapy study 奥罗芬明与唑类抗真菌药联合使用：2期挽救治疗研究结果 Johan Maertens and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag118, https://doi.org/10.1093/jac/dkag118 RESEARCH LETTER（研究快讯） 43 Infant HIV transmission despite maternal viral suppression: a case of post-weaning seroconversion 母体病毒得到抑制，婴儿仍发生HIV传播：一例断奶后血清转阳病例 Shadia Nakalema and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag072, https://doi.org/10.1093/jac/dkag072 44 Urinary antigen–negative Legionella pneumonia in critically ill patients: value of systematic molecular testing for optimal antimicrobial therapy 危重患者中尿抗原阴性军团菌肺炎：系统分子检测在优化抗菌治疗中的价值 Livia Foglia Manzillo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag101, https://doi.org/10.1093/jac/dkag101 45 Contribution of SHV-1 overexpression to carbapenem resistance in a Klebsiella pneumoniae clinical isolate SHV-1过表达对某株肺炎克雷伯菌临床分离株碳青霉烯类抗生素耐药性的影响 Céline Plainvert and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag108, https://doi.org/10.1093/jac/dkag108 LETTER TO THE EDITOR（致编辑的信） 46 Comment on: Possible increased risk of Epstein–Barr virus (EBV) infection and posttransplant lymphoproliferative disease (PTLD) in letermovir-exposed haematopoietic cell transplantation recipients 评论：接受莱特莫韦治疗的造血细胞移植受者中，EB病毒（EBV）感染和移植后淋巴增殖性疾病（PTLD）的风险可能增加 Jan Styczynski Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag042, https://doi.org/10.1093/jac/dkag042 47 Comment on: Antimicrobial use for the treatment of bacterial sexually transmitted infections among doxycycline post-exposure prophylaxis users in Milan, Italy 评论：意大利米兰地区使用多西环素暴露后预防措施人群中针对细菌性性传播感染的抗菌药物使用情况 Luca Bortolani and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag023, https://doi.org/10.1093/jac/dkag023 48 Retrospective analysis of pharmacological therapeutic monitoring of caspofungin in patients undergoing continuous renal replacement therapy using polyacrylonitrile membranes—right to reply 使用聚丙烯腈膜进行连续肾脏替代治疗的患者中卡泊芬净药物治疗监测的回顾性分析——答复权 Antoine Hérault and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag095, https://doi.org/10.1093/jac/dkag095 49 Comment on: Temocillin versus other intravenous beta-lactams for urinary tract infections caused by third-generation cephalosporin-resistant Enterobacterales: a multicentre retrospective matched-cohort study 评论：替莫西林与其他静脉注射β-内酰胺类抗生素治疗第三代头孢菌素耐药肠杆菌目引起的尿路感染：一项多中心回顾性匹配队列研究 Shanshan Ru and Yingzhe Zhang Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag096, https://doi.org/10.1093/jac/dkag096 50 Comment on: Long-acting glycopeptides: what are the barriers to access in patients who need them most, and how can they be overcome? 评论：长效糖肽类抗生素：对于最需要它们的患者，获取的障碍是什么，如何克服？ Marco Bongiovanni Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag102, https://doi.org/10.1093/jac/dkag102 51 Comment on ‘Retrospective analysis of pharmacological therapeutic monitoring of caspofungin in patients undergoing continuous renal replacement therapy using polyacrylonitrile membranes’ 评论：“对使用聚丙烯腈膜进行连续肾脏替代治疗的患者中卡泊芬净的药理学治疗监测的回顾性分析” Julien Massol and Frédéric Baud Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag094, https://doi.org/10.1093/jac/dkag094 52 Comment on: ‘Epidemiology and treatment of endocarditis secondary to Enterobacterales other than Serratia spp’ 对“除塞拉蒂亚属（Serratia spp）外肠杆菌目所致心内膜炎的流行病学和治疗”的评论 Gianpiero Tebano and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag098, https://doi.org/10.1093/jac/dkag098 53 ‘Comparing serotype coverage of pneumococcal vaccines with PCV21 (V116), a new 21-valent conjugate pneumococcal vaccine, and the epidemiology of its eight unique Streptococcus pneumoniae serotypes (15A, 15C, 16F, 23A, 23B, 24F, 31 and 35B) causing invasive pneumococcal disease in adult patients in Canada: SAVE study, 2018–2021-right-to-reply’ “比较肺炎球菌疫苗的血清型覆盖率——PCV21（V116，一种新型21价结合肺炎球菌疫苗）与加拿大成人患者中导致侵袭性肺炎球菌疾病的其8种独特肺炎链球菌血清型（15A、15C、16F、23A、23B、24F、31和35B）的流行病学：SAVE研究，2018 - 2021年——回应” John J Schellenberg and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag126, https://doi.org/10.1093/jac/dkag126 54 Comment on: Antagonistic in vitro interaction between olorofim and voriconazole against Aspergillus fumigatus 评论：奥罗芬明与伏立康唑对烟曲霉的体外拮抗作用 Corinne Pinder and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag119, https://doi.org/10.1093/jac/dkag119 55 Epidemiology and treatment of endocarditis secondary to Enterobacterales other than Serratia spp.: right-to-reply 除塞氏杆菌属外肠杆菌科细菌所致心内膜炎的流行病学和治疗：回应 Sunish Shah and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag121, https://doi.org/10.1093/jac/dkag121 Journal of Antimicrobial Chemotherapy Volume 81, Issue 5抗菌化疗杂志81卷 5期 https://academic.oup.com/jac/issue 50TH ANNIVERSARY COLLECTION（50周年纪念合集） REVIEW（综述） 1 A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 1: setting the stage 针对动基体病的高质量先导化合物及药物开发候选物的战略发现路线图。第一部分：背景介绍 Sarah Hendrickx and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag109, https://doi.org/10.1093/jac/dkag109 REVIEW（综述） 2 Pathophysiology, risk factors and clinical management for polymyxin-associated acute kidney injury 多粘菌素相关急性肾损伤的病理生理学、危险因素及临床治疗 Simiao Zhao and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag132, https://doi.org/10.1093/jac/dkag132 SYSTEMATIC REVIEW（系统综述） 3 Definitions and rates of treatment failure in females with uncomplicated urinary tract infection: a systematic literature review 女性单纯性尿路感染治疗失败的定义及发生率：一项系统文献综述 Meghan E Luck and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag112, https://doi.org/10.1093/jac/dkag112 4 Therapeutic drug monitoring and the role of pharmacokinetics/pharmacodynamics in optimizing beta-lactam antibiotic dosing for deep-seated infections: a systematic review 在针对深部感染的β-内酰胺类抗生素优化给药方案中治疗药物监测以及药代动力学/药效学的作用：一项系统综述 Cassandra Vale and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag142, https://doi.org/10.1093/jac/dkag142 ORIGINAL RESEARCH（论著） 5 Optimizing cloxacillin prophylaxis in hip and knee arthroplasty based on population pharmacokinetics of unbound plasma concentrations 基于游离血浆浓度群体药代动力学优化髋关节和膝关节置换术中的氯唑西林预防用药方案 Gustaf Beijer and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag116, https://doi.org/10.1093/jac/dkag116 6 The tissue distribution and pharmacokinetics of [14C]-olorofim following intravenous dosing in the rat 大鼠静脉注射[14C]奥洛罗芬后的组织分布及药代动力学研究 Derek Law and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag120, https://doi.org/10.1093/jac/dkag120 7 Insights from the WHO Tricycle-aligned Fleming Fund EQASIA External Quality Assessment (EQA) programme detecting ESBL-, AmpC- and carbapenemase-producing Escherichia coli in South and South-East Asia 世界卫生组织三轮车项目（Tricycle）协同的弗莱明基金南亚和东南亚地区外部质量评估（EQASIA EQA）计划在检测南亚和东南亚地区产超广谱β-内酰胺酶（ESBL）、AmpC酶和碳青霉烯酶的大肠埃希菌方面的见解 Hiba Al-Mir and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag129, https://doi.org/10.1093/jac/dkag129 8 The plasma and intracellular exposure of intramuscularly administered long-acting cabotegravir and rilpivirine in people with HIV HIV感染者肌内注射长效卡博特韦和利匹韦林后的血浆及细胞内暴露情况 Micol Ferrara and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag113, https://doi.org/10.1093/jac/dkag113 9 In vitro synergistic activity of minocycline and biapenem against cefiderocol-resistant New Delhi metallo-β-lactamase-producing Enterobacterales 米诺环素与比阿培南在体外对产新德里金属β-内酰胺酶且对头孢地尔耐药的肠杆菌科细菌的协同作用 Takashi Okanda and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag128, https://doi.org/10.1093/jac/dkag128 10 Mortality risk of ESBL producers in Escherichia coli bacteraemia: a comprehensive analysis using the PROBAC cohort 产超广谱β-内酰胺酶大肠埃希菌菌血症的死亡风险：基于PROBAC队列的综合分析 Paula Olivares-Navarro and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag130, https://doi.org/10.1093/jac/dkag130 11 Molecular mechanism of envZ regulating β-lactam antibiotic resistance and virulence in Escherichia coli EnvZ调控大肠埃希菌β-内酰胺类抗生素耐药性及毒力的分子机制 Kun Yang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag104, https://doi.org/10.1093/jac/dkag104 12 In vitro activity of amoxicillin combined with oral cephalosporins against endocarditis-associated E. faecalis clinical isolates 阿莫西林联合口服头孢菌素针对心内膜炎相关粪肠球菌临床分离株的体外活性 David Luque Paz and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag127, https://doi.org/10.1093/jac/dkag127 13 Genome-wide association studies builds a predictive model and reveals novel resistance features for macrolide-resistant Bordetella pertussis 全基因组关联研究构建预测模型并揭示大环内酯类耐药百日咳鲍特菌的新耐药特征 Jialiang Chen and Guowei Liang Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag131, https://doi.org/10.1093/jac/dkag131 14 Real-world validation of a reduced-dose continuous infusion cefepime regimen: pharmacodynamic target attainment, efficacy and neurotoxicity 减量持续静脉输注头孢吡肟方案的实际应用验证：药效学目标达成情况、疗效及神经毒性 Kieffer Korvin and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag138, https://doi.org/10.1093/jac/dkag138 15 Cross-species and cross-border spread of aph(3′)-ia-mediated neomycin resistance in Escherichia coli from animals: a genomic perspective 从基因组角度研究动物源大肠杆菌中aph(3′)-ia介导的新霉素耐药性的跨物种和跨国传播 Mattia Pirolo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag143, https://doi.org/10.1093/jac/dkag143 16 Prevalence of cyp51A variants in a US collection of Aspergillus fumigatus clinical isolates and comparative analysis of their contribution to triazole antifungal resistance 美国烟曲霉临床分离株集合中cyp51A变异体的流行情况及其对三唑类抗真菌药物耐药性作用的比较分析 Luisa Fernanda Gómez Londoño and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag124, https://doi.org/10.1093/jac/dkag124 17 In vitro and in vivo activity of daptomycin plus ceftaroline for the treatment of experimental endocarditis due to Enterococcus faecalis with and without high-level aminoglycoside resistance 达托霉素联合头孢洛林对高水平氨基糖苷类耐药及非耐药粪肠球菌所致实验性心内膜炎的体内外疗效研究 María-Alexandra Cañas and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag136, https://doi.org/10.1093/jac/dkag136 18 Pharmacokinetics of a three-dose regimen of intramuscular benzathine penicillin G in pregnant women with syphilis 三剂苄星青霉素G肌内注射方案在妊娠期梅毒患者中的药代动力学研究 Eshetie Melese Birru and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag145, https://doi.org/10.1093/jac/dkag145 19 Cefiderocol resistance mediated by mutation of the miniconductance mechanosensitive channel MscM in Klebsiella oxytoca 由产气克雷伯菌中微小电导机械敏感通道MscM发生突变所介导的头孢地尔耐药性 Pia Turowski and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag147, https://doi.org/10.1093/jac/dkag147 20 The veterinary clinic backyard lawn used for relief walks of hospitalized dogs is a hotspot for OXA-type carbapenemases in multiple Enterobacterales 兽医诊所后院供住院犬只散步的草坪是多种肠杆菌科细菌中OXA型碳青霉烯酶的传播热点区域 Yvonne Spahr and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag144, https://doi.org/10.1093/jac/dkag144 21 Pharmacokinetics of cefazolin in bariatric surgery patients: a preoperative perspective 头孢唑林在减肥手术患者中的药代动力学：术前视角 Alexandra Porlier and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag150, https://doi.org/10.1093/jac/dkag150 RESEARCH LETTERS（研究快讯） 22 Plasmid-encoded FRI-10 carbapenemase harboured by non-Enterobacter species isolated from a wastewater sample in Tokyo, Japan 从日本东京废水样本中分离出的非肠杆菌科物种携带质粒编码的FRI-10碳青霉烯酶 Kou Murakami and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag133, https://doi.org/10.1093/jac/dkag133 23 Synergistic activity of cefepime/enmetazobactam with meropenem, piperacillin, piperacillin/tazobactam, cefiderocol and fosfomycin against Klebsiella pneumoniae carrying blaKPC allelic variants 头孢吡肟/恩美唑巴坦与美罗培南、哌拉西林、哌拉西林/他唑巴坦、西他沙星和磷霉素针对携带blaKPC等位基因变体的肺炎克雷伯菌的协同作用 Alice Crema and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag141, https://doi.org/10.1093/jac/dkag141 24 MRSA and carbapenem-resistant Acinetobacter baumannii on the fall: successful infection prevention and control in Chilean ICUs 耐甲氧西林金黄色葡萄球菌和耐碳青霉烯类鲍曼不动杆菌数量下降：智利重症监护病房感染预防与控制的成功案例 Patricio Ross and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag146, https://doi.org/10.1093/jac/dkag146 LETTER TO THE EDITOR（致编辑的信） 25 Comment on: Model-based assessment of VRC07-523LS dosing in infants through population pharmacokinetic–pharmacodynamic modelling in adults and infants 评论：基于模型的评估VRC07-523LS在婴儿中的给药剂量——基于成人和婴儿群体药代动力学-药效学模型 Wanhua Qiu Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag139, https://doi.org/10.1093/jac/dkag139 26 Comment on: Comparing serotype coverage of pneumococcal vaccines with PCV21 (V116), a new 21-valent conjugate pneumococcal vaccine, and the epidemiology of its eight unique Streptococcus pneumoniae serotypes (15A, 15C, 16F, 23A, 23B, 24F, 31 and 35B) causing invasive pneumococcal disease in adult patients in Canada: SAVE study, 2018–21 评论：比较含21种血清型的肺炎球菌疫苗PCV21（V116）（一种新型21价结合肺炎球菌疫苗）的血清型覆盖范围，以及2018 - 2021年SAVE研究中导致加拿大成年患者侵袭性肺炎球菌疾病的8种独特肺炎链球菌血清型（15A、15C、16F、23A、23B、24F、31和35B）的流行病学情况 Gokul Raj Pullagura and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag125, https://doi.org/10.1093/jac/dkag125 27 Comment on: Distinct population structure and genomic context of NarAB between broiler and human clinical Enterococcus isolates 评论：肉鸡源和人临床来源肠球菌分离株中NarAB的不同种群结构和基因组背景 Alex Wong Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag134, https://doi.org/10.1093/jac/dkag134 28 Distinct population structure and genomic context of narAB between broiler and human clinical Enterococcus isolates—authors’ response 肉鸡源和人临床来源肠球菌分离株中narAB的不同种群结构和基因组背景——作者回复 Jayanth Balakuntla and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag135, https://doi.org/10.1093/jac/dkag135 Journal of Antimicrobial Chemotherapy Volume 81, Issue 6抗菌化疗杂志81卷 6期 https://academic.oup.com/jac/issue 50TH ANNIVERSARY COLLECTION（50周年纪念合集） REVIEW（综述） 1 A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 3: from lead towards a drug development candidate 针对动基体疾病高质量先导化合物和药物开发候选物的战略发现路线图。第三部分：从先导化合物到药物开发候选物 Sarah Hendrickx and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag111, https://doi.org/10.1093/jac/dkag111 ORIGINAL RESEARCH（原创研究） 2 Population pharmacokinetics and probability of target attainment of tigecycline in critically ill children 危重患儿中替加环素（Tigecycline）的群体药代动力学及目标达成概率研究 Wenjuan Hu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag156, https://doi.org/10.1093/jac/dkag156 3 Phenotypic and genotypic characterization of HMB-3, a metallo-beta-lactamase from Pseudomonas asiatica 假单胞菌属亚洲种（Pseudomonas asiatica）中金属β-内酰胺酶HMB-3的表型和基因型特征 Jacqueline Findlay and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag148, https://doi.org/10.1093/jac/dkag148 4 Early adequate linezolid concentrations and clinical outcomes in confirmed Gram-positive infections: the role of therapeutic drug monitoring 确诊的革兰氏阳性菌感染中早期达到适宜利奈唑胺浓度与临床预后的关系：治疗药物监测的作用 Daniel Fresán and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag137, https://doi.org/10.1093/jac/dkag137 5 Monte Carlo simulations identify suboptimal PK/PD target attainment with standard maribavir dosing 蒙特卡洛模拟表明标准剂量马立巴韦的药动学/药效学靶标达成情况欠佳 Yeleen Fromage and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag153, https://doi.org/10.1093/jac/dkag153 6 Exploring the pharmacokinetic mechanisms that affect bictegravir exposure during pregnancy 探究妊娠期间影响比克替拉韦暴露的药代动力学机制 L van der Wekken-Pas and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag159, https://doi.org/10.1093/jac/dkag159 7 Artificial intelligence for analysing antibiotic use: an exploratory study in a tertiary care paediatric hospital in Italy 人工智能用于分析抗生素使用情况：意大利一家三级儿科医院的探索性研究 Elio Castagnola and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag162, https://doi.org/10.1093/jac/dkag162 8 Antimicrobial activity of aztreonam–avibactam against KPC variant-producing Klebsiella pneumoniae with ceftazidime–avibactam resistance 氨曲南-阿维巴坦对产KPC变异体且对头孢他啶-阿维巴坦耐药的肺炎克雷伯菌的抗菌活性 Jingchun Kong and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag152, https://doi.org/10.1093/jac/dkag152 9 Highly transformable Haemophilus influenzae as a potential amplifier of quinolone resistance dissemination 高转化型流感嗜血杆菌作为喹诺酮耐药性传播的潜在放大器 Takeaki Wajima and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag160, https://doi.org/10.1093/jac/dkag160 10 Comparative nephrotoxicity of polymyxin B versus colistin: evidence from ensemble learning and propensity score matching 多黏菌素B与黏菌素的肾毒性比较：来自集成学习和倾向评分匹配的证据 Murat Özdede and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag044, https://doi.org/10.1093/jac/dkag044 11 Emulating a target trial of early compared with late initiation of appropriate antibiotic therapy for hospital-acquired monobacterial Gram-negative bloodstream infections 模拟医院获得性单菌革兰氏阴性菌血流感染早期与晚期开始恰当抗生素治疗的对照试验 Abdullah T Aslan and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag161, https://doi.org/10.1093/jac/dkag161 12 Flufenamic acid resensitizes MRSA to gentamicin through synergistic ion modulation 氟苯尼考通过协同离子调节使MRSA对庆大霉素重新敏感 Xiaomin Ren and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag154, https://doi.org/10.1093/jac/dkag154 13 Description of OXA-244 carbapenemase-producing Escherichia coli in farm animals in The Netherlands, 2024 2024年荷兰农场动物中OXA-244碳青霉烯酶产大肠杆菌的描述 K T Veldman and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag155, https://doi.org/10.1093/jac/dkag155 14 Clinical outcomes of beta-bactam monotherapy versus beta-lactam plus azithromycin in hospitalized patients with community-acquired pneumoniae β-内酰胺类单药治疗与β-内酰胺类联合阿奇霉素治疗社区获得性肺炎住院患者的临床预后比较 Ilona Zhygalova Zhygalova and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag158, https://doi.org/10.1093/jac/dkag158 15 ‘Leaving no stones unturned’: up to 10 years results on the effectiveness, tolerability and metabolic safety of dolutegravir+lamivudine (DTG+3TC) as a switch regimen in the ODOACRE cohort "不遗余力"：ODOACRE队列中多替拉韦+拉米夫定（DTG+3TC）作为转换方案长达10年的有效性、耐受性及代谢安全性结果 Arturo Ciccullo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag172, https://doi.org/10.1093/jac/dkag172 16 Evaluation of a novel lateral flow immunochromatographic assay, Certest ResisCheck® Carbapenemases, for the rapid detection and differentiation of carbapenemase in Gram-negative bacteria from bacterial culture 新型侧向流免疫层析检测试剂Certest ResisCheck® Carbapenemases用于革兰氏阴性菌培养物中碳青霉烯酶快速检测与鉴别的评估 Laura Monge-Olivares and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag149, https://doi.org/10.1093/jac/dkag149 17 Temocillin efficacy and emergence of resistance in Enterobacter cloacae Complex in a murine peritonitis model 替莫西林对产气肠杆菌复合群的疗效及耐药性演变：小鼠腹膜炎模型研究 N Alanbari and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag151, https://doi.org/10.1093/jac/dkag151 18 Temporal association between aerosolized colistin use and colistin resistance in the ICU: a time-series analysis ICU中雾化粘菌素使用与粘菌素耐药之间的时间关联：一项时间序列分析 Weechang Kang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag169, https://doi.org/10.1093/jac/dkag169 19 Can antimicrobial stewardship programmes be implemented during an armed conflict? A retrospective interventional cohort study 武装冲突期间能否实施抗菌药物管理计划？一项回顾性干预性队列研究 Hailie D Uren and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag115, https://doi.org/10.1093/jac/dkag115 20 Voriconazole therapy and CYP2C19 phenotype: identifying patients who may need alternative antifungal therapy 伏立康唑治疗与CYP2C19表型：识别可能需要替代抗真菌治疗的患者 Eman Wehbe and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag168, https://doi.org/10.1093/jac/dkag168 21 Impact of cardiopulmonary bypass on cefuroxime plasma and interstitial tissue concentrations in patients undergoing cardiac bypass surgery—a prospective controlled clinical trial 体外循环对心脏旁路手术患者头孢呋辛血浆及组织间质浓度的影响——一项前瞻性对照临床试验 Stefanie Nothofer and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag171, https://doi.org/10.1093/jac/dkag171 22 Population pharmacokinetic analysis and dosing regimen optimization of eravacycline in critically ill patients with carbapenem-resistant Acinetobacter baumannii pneumonia 对碳青霉烯耐药鲍曼不动杆菌肺炎危重患者中埃拉环素的药代动力学分析及给药方案优化 Luqi Lou and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag178, https://doi.org/10.1093/jac/dkag178 23 Durability and mechanistic performance of aztreonam/avibactam versus aztreonam plus ceftazidime/avibactam against Stenotrophomonas maltophilia complex 氨曲南/阿维巴坦与氨曲南联合头孢他啶/阿维巴坦对抗嗜麦芽窄食单胞菌复合群的耐久性和机制性能比较 Ashlan J Kunz Coyne and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag177, https://doi.org/10.1093/jac/dkag177 24 High-dose daptomycin for the treatment of invasive infections due to Enterococcus faecalis isolates with intermediate susceptibility 高剂量达托霉素治疗粪肠球菌中介敏感株所致侵袭性感染的疗效 Sidney Drake and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag179, https://doi.org/10.1093/jac/dkag179 25 Updated mapping of Plasmodium falciparum kelch13 gene polymorphisms in Madagascar, 2024 2024年马达加斯加恶性疟原虫kelch13基因多态性的最新图谱更新 Camille Roesch and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag181, https://doi.org/10.1093/jac/dkag181 26 Efficacy of ceftazidime/avibactam against 10 clinical isolates of Pseudomonas aeruginosa in icodextrin-based peritoneal dialysis solution and patient-derived dialysate 头孢他啶/阿维巴坦针对icodextrin基腹膜透析液及患者来源透析液中10株铜绿假单胞菌临床分离株的抗菌活性 Stephanie Supparitsch and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag185, https://doi.org/10.1093/jac/dkag185 27 Cefiderocol activity against multidrug-resistant isolates from the PERSEUS study: relationship between cefiderocol minimum inhibitory concentration and clinical outcomes 头孢德罗对PERSEUS研究中多重耐药分离株的抗菌活性：头孢德罗最低抑菌浓度与临床预后之间的关系 Rafael Cantón and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag164, https://doi.org/10.1093/jac/dkag164 28 Class 1 DISARM system in restriction of conjugative carbapenemase-encoding plasmids in Klebsiella pneumoniae sequence type 23 1类DISARM系统对肺炎克雷伯菌ST23中接合型碳青霉烯酶编码质粒的限制作用 Qingqing Du and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag167, https://doi.org/10.1093/jac/dkag167 29 Acute kidney injury following amikacin therapy: a retrospective cohort study 阿米卡星治疗后急性肾损伤：一项回顾性队列研究 Iris Zohar and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag188, https://doi.org/10.1093/jac/dkag188 30 Performance of EUCAST disc diffusion and supplementary methods to detect reduced susceptibility to linezolid in enterococci— the NordicAST LRE-study EUCAST纸片扩散法及补充方法检测肠球菌利奈唑胺低敏感性的表现——NordicAST LRE研究 Bjørg Christina Haldorsen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag174, https://doi.org/10.1093/jac/dkag174 31 In vitro exposure to non-antipseudomonal antibiotics (NAPA) induces Pseudomonas aeruginosa resistance to antipseudomonal antibiotics (APA) 体外暴露于非抗假单胞菌抗生素（NAPA）可诱导铜绿假单胞菌对抗假单胞菌抗生素（APA）产生耐药性 David Lasry and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag182, https://doi.org/10.1093/jac/dkag182 32 Sub-inhibitory polyether ionophores enhance resistance plasmid transfer and transiently perturb the broiler gut resistome 亚抑制浓度的聚醚离子载体可促进耐药质粒转移并暂时扰乱肉鸡肠道耐药组 Jingyue Yang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag190, https://doi.org/10.1093/jac/dkag190 33 Influence of a putative TonB-dependent receptor on cefiderocol susceptibility in clinical Enterobacter hormaechei isolates 推测的TonB依赖性受体对临床肠杆菌hormaechei分离株中头孢地尔敏感性的影响 Pia Turowski and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag193, https://doi.org/10.1093/jac/dkag193 RESEARCH LETTERS（研究快报） 34 Early bictegravir failure and emergence of R263K-mediated class-wide HIV integrase inhibitors resistance linked to over-the-counter supplement use 比克替拉韦早期治疗失败与R263K介导的与非处方补充剂使用相关的全类HIV整合酶抑制剂耐药的出现 Elisa Minacori and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag157, https://doi.org/10.1093/jac/dkag157 35 Environmental benefits of switching from intravenous to oral administration of ciprofloxacin 环丙沙星从静脉给药转换为口服给药的环境效益 Nicolas De Jaegher and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag163, https://doi.org/10.1093/jac/dkag163 36 Macrolide resistance via 23S rRNA gene mutation in Corynebacterium ulcerans 白喉棒状杆菌通过23S rRNA基因突变介导的大环内酯类耐药 Chiara Crestani and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag166, https://doi.org/10.1093/jac/dkag166 37 Prosthesis-associated Burkholderia cepacia complex infection managed with sequential directed therapy including ceftolozane/tazobactam 采用包括头孢妥仑/他唑巴坦在内的序贯导向疗法治疗假体相关洋葱伯克霍尔德菌复合感染 Elia Asensi-Díaz and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag165, https://doi.org/10.1093/jac/dkag165 38 Drug interactions and kidney safety of bictegravir/emtricitabine/tenofovir alafenamide in kidney transplant recipients with HIV: an interventional pilot study 比克替拉韦/恩曲他滨/丙酚替诺福韦在合并HIV的肾移植受者中的药物相互作用及肾脏安全性：一项干预性 pilot 研究 Thomas Stehlé and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag176, https://doi.org/10.1093/jac/dkag176 39 Harmonizing antimicrobial susceptibility testing: a comparison of CLSI and EUCAST categorizations 抗菌药物敏感性试验的协调：CLSI与EUCAST分类法的比较 Eric Farfour and Marie Lavollay Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag081, https://doi.org/10.1093/jac/dkag081 LETTER TO THE EDITOR（致编辑的信） 40 Comment on: Impact of loading dose β-lactam therapy on outcomes of KPC-producing Klebsiella pneumoniae bloodstream infections in non-ICU patients: a real world study 对"负荷剂量β-内酰胺类治疗对非ICU患者产KPC肺炎克雷伯菌血流感染结局的影响：一项现实研究"的评论 Xuefeng Yu Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag173, https://doi.org/10.1093/jac/dkag173 41 Comment on: ‘Cooperation between HIV-1 integrase natural polymorphism K156N and 3′PPT mutations in dolutegravir monotherapy failure’ 评论："HIV-1整合酶天然多态性K156N与3′PPT突变在多替拉韦单药治疗失败中的协同作用" Muhammad Ifham Hanif and Mentari Maratus Sholihah Journal of Antimicrobial Chemotherapy, Volume 81, Issue 6, June 2026, dkag175, https://doi.org/10.1093/jac/dkag175

2026-06-09

·我药说说

达尔西利（恒瑞原研）：中国首个获批上市的国产原研CDK4/6抑制剂

每天学一味药：达尔西利（Dalpiciclib）一、概括性总结达尔西利（Dalpiciclib，研发代号SHR6390）是由江苏恒瑞医药自主研发的、中国首个获批上市的国产原研CDK4/6抑制剂，于2021年12月获得国家药品监督管理局（NMPA）附条件批准上市，商品名"艾瑞康"[1]。作为高选择性、口服小分子CDK4/6抑制剂，达尔西利通过选择性抑制细胞周期蛋白依赖性激酶4和6（CDK4/6），阻断Rb蛋白磷酸化及E2F转录因子释放，从而将肿瘤细胞阻滞于G1期，抑制其增殖[2,3]。其核心临床价值在于：DAWNA-1和DAWNA-2两项III期研究分别验证了达尔西利联合氟维司群或来曲唑在HR+/HER2-晚期乳腺癌中超越单独内分泌治疗的显著疗效[4,5]。2023年6月，达尔西利获NMPA完全批准，标志着中国在CDK4/6抑制剂领域实现了从跟跑到并跑的跨越。与同类药物相比，达尔西利具有独特的药代动力学特征（每天一次给药、半衰期约44小时）和差异化的安全性谱（肝功能影响较小，以可逆性血液学毒性为主），且DAWNA-2研究证实其对绝经前/围绝经期患者同样有效[5]。对于每一位关注肿瘤药理学前沿的药学人而言，达尔西利是理解"细胞周期调控靶向治疗"从机制到临床转化的经典范例。二、目录一、概括性总结二、目录三、药物概览（药物档案）四、药理作用机制 - 4.1 分子机制：CDK4/6-Rb-E2F信号轴的选择性阻断 - 4.2 CDK家族成员及其功能分布 - 4.3 对各器官系统的药理作用分述五、临床适应症六、临床应用Tips 七、不良反应与禁忌症八、剂量与用法速查表九、药学考点速记十、参考文献三、药物概览（药物档案）药物档案表项目内容通用名（中文）达尔西利通用名（英文） Dalpiciclib商品名艾瑞康（Airuikang）研发代号 SHR6390化学结构/结构类型小分子化合物，属于吡啶并[2,3-d]嘧啶类衍生物；核心骨架为2-氨基吡啶嘧啶结构，含N-取代哌啶侧链和氟代苯基修饰[2]分子式 C25H30F3N7O2[6]分子量约517.5 Da[6]药物分类抗肿瘤药；细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6 inhibitor）ATC编码 L01EF03（CDK4/6抑制剂类）来源/原研企业全合成来源；原研企业：江苏恒瑞医药股份有限公司（Jiangsu Hengrui Medicine Co., Ltd.）剂型规格片剂：50 mg、75 mg、100 mg、125 mg、150 mg[7]给药途径口服（PO）生物利用度口服吸收良好，绝对生物利用度数据未完整披露；食物不影响其吸收程度（高脂餐可轻微延迟Tmax），可空腹或随餐服用[8]血浆蛋白结合率约97%，主要与白蛋白和α1-酸性糖蛋白结合分布容积（Vd）约2580 L（表观分布容积），提示广泛组织分布半衰期（t½）约44小时（范围37-54小时），支持每日一次给药Tmax 约5-8小时（空腹）；高脂餐后约8-12小时[8]代谢途径主要经CYP3A4代谢，少量经CYP2D6代谢；代谢产物包括N-去甲基化、N-氧化及羟基化产物；代谢物药理学活性显著低于母药[8]排泄主要经粪便排泄（约70%），经肾脏排泄约20%；原形药物在尿液中含量极低（<1%）清除率（CL/F）约39.4 L/h（表观口服清除率）妊娠分级（FDA）尚未获得FDA妊娠分级；基于作用机制，可能致胎儿损伤；育龄期女性治疗期间及末次给药后至少3周内应采取有效避孕措施[7]储存条件密封、常温（10-30°C）干燥处保存药物地位简述达尔西利是中国首个自主研发并获批上市的CDK4/6抑制剂，也是全球第四个、中国第二个获批的CDK4/6抑制剂（前三个全球获批者为Palbociclib/哌柏西利、Ribociclib/瑞博西利、Abemaciclib/阿贝西利）[1,2]。在HR+/HER2-晚期乳腺癌的内分泌治疗领域，CDK4/6抑制剂联合内分泌治疗已成为标准一线方案，被NCCN指南（2023 v4）、ASCO指南及《中国抗癌协会乳腺癌诊治指南与规范》（CBCS 2023版）一致推荐[9,10]。达尔西利的问世不仅填补了国产CDK4/6抑制剂的空白，使中国患者获得可及性更高、治疗费用更低的选择，更在DAWNA-2研究中证实其对绝经前/围绝经期患者的疗效（该人群在Palbociclib的PALOMA系列研究中数据有限）[5]。四、药理作用机制 4.1 分子机制：CDK4/6-Rb-E2F信号轴的选择性阻断 4.1.1 细胞周期调控的分子基础真核细胞周期的进程由一系列细胞周期蛋白依赖性激酶（Cyclin-dependent kinases, CDKs）精密调控。在G1期向S期过渡的关键限制点（Restriction point, R点），细胞周期蛋白D（Cyclin D）与CDK4/6形成具有激酶活性的全酶复合物（Cyclin D-CDK4/6 holoenzyme），催化视网膜母细胞瘤蛋白（Retinoblastoma protein, pRb）的磷酸化[3]。具体过程分三步：第一步——Cyclin D-CDK4/6复合物的组装与激活：在促有丝分裂信号（如雌激素受体信号通路、PI3K-AKT-mTOR通路、RAS-MAPK通路）的刺激下，Cyclin D（D1/D2/D3亚型）表达上调。Cyclin D与CDK4/6结合后，引起CDK4/6的T-loop构象改变，暴露出ATP结合位点。CDK激活激酶（CAK，即CDK7-Cyclin H-MAT1复合物）进一步磷酸化CDK4/6的T-loop上的苏氨酸残基（如CDK4的Thr172），使全酶获得完全催化活性[11]。第二步——pRb的低磷酸化与高磷酸化：初始阶段，活化的Cyclin D-CDK4/6使pRb发生低磷酸化（hypophosphorylation）——pRb的C端多个丝氨酸/苏氨酸位点（如Ser780、Ser795、Ser807/811）被顺序磷酸化。低磷酸化的pRb仍部分维持与E2F转录因子的结合能力，但结合力减弱。随着G1期的推进，Cyclin E-CDK2进一步催化pRb的高磷酸化（hyperphosphorylation），使pRb完全失活并与E2F解离[11,12]。第三步——E2F释放及G1/S转换：释放后的E2F（主要为E2F1-E2F3）从细胞质转入细胞核，与二聚化伴侣蛋白DP结合，反式激活一系列S期必需基因的转录，包括Cyclin E、Cyclin A、DNA聚合酶α、胸苷激酶（TK1）、二氢叶酸还原酶（DHFR）等。这一转录程序的启动标志着细胞不可逆地越过R点，进入S期[12]。达尔西利的作用靶点恰位于上述级联反应的"上游开关"——通过选择性抑制CDK4/6的ATP结合位点，阻止Cyclin D-CDK4/6全酶对pRb的初始磷酸化，从而在G1/S检查点处"锁定"细胞周期进程。 4.1.2 达尔西利的分子结合特征达尔西利是一种ATP竞争性、可逆性CDK4/6抑制剂[2]。结合模式： - 达尔西利以ATP竞争性方式与CDK4和CDK6的ATP结合口袋结合，与铰链区的Val残基形成关键氢键 - 其2-氨基吡啶嘧啶核心与CDK6的铰链区（Hinge region, His100-Val101）形成bidentate氢键网络；N-取代哌啶侧链占据溶剂暴露区，提供选择性调控 - 对CDK4的IC50约为12.4 nM，对CDK6的IC50约为9.9 nM——对CDK6的亲和力略高于CDK4[1,2] 选择性特征：激酶靶点 IC50（nM）选择性倍数（vs CDK6） CDK6 9.9 1× CDK4 12.4 1.25× CDK2 >1000 >100× CDK1 >5000 >500× CDK7 >10000 >1000× CDK9 >1000 >100× 数据来源：基于恒瑞医药公开的临床前药理学数据[1,2]。关键药理学意义： - 高选择性意味着对其他CDK家族成员的"脱靶（off-target）"抑制极弱，降低了广谱CDK抑制剂常见的骨髓外毒性 - 对CDK2的高选择性比（>100×）尤为重要：CDK2-Cyclin E复合物是G1/S转换的补充调节因子，保留CDK2活性意味着正常增殖活跃的组织（如肠上皮、毛囊）仍可部分通过CDK2代偿，从而减轻胃肠道和皮肤毒性[12] 4.1.3 药效学特征药效学参数数据作用类型 ATP竞争性、可逆性CDK4/6抑制剂与CDK4/6的结合特征竞争性抑制（增加ATP浓度可逆转抑制）对CDK4/6的内在活性无内在活性（纯拮抗剂），不激活下游信号 G1期阻滞的诱导浓度 50-150 nM即可在ER+乳腺癌细胞系（MCF-7、T47D）中诱导显著的G0/G1期阻滞诱导细胞衰老在持续给药（>72 h）后可在部分敏感细胞系中诱导SA-β-gal阳性细胞衰老表型[2] 与内分泌治疗的协同性与氟维司群（选择性ER降解剂）或来曲唑（芳香化酶抑制剂）联用在体外和体内模型中均显示协同（synergistic）抗增殖效应，而非简单叠加[2] 4.1.4 达尔西利独特的作用特点与同类比较特征达尔西利（Dalpiciclib）哌柏西利（Palbociclib）瑞博西利（Ribociclib）阿贝西利（Abemaciclib）对CDK4的IC50 ~12.4 nM ~11 nM ~10 nM ~2 nM 对CDK6的IC50 ~9.9 nM ~15 nM ~39 nM ~5 nM CDK4/CDK6选择性比 ~1.25 ~1.36 ~3.9 ~2.5 CDK9抑制（IC50） >1000 nM >5000 nM >5000 nM ~57 nM 给药频率每日一次每日一次每日一次每日两次半衰期 ~44 h ~29 h ~32 h ~18 h CYP3A4底物是是是是血脑屏障穿透数据有限有限有限有（部分）常见DLT 中性粒细胞减少中性粒细胞减少中性粒细胞减少腹泻、中性粒细胞减少关键差异点分析：（1）达尔西利 vs 哌柏西利：两者均为高选择性CDK4/6抑制剂，但达尔西利的半衰期更长（44 h vs 29 h），理论上对服药时间误差的容忍度更高。达尔西利在DAWNA-2研究中纳入了绝经前/围绝经期患者（联用OFS），而PALOMA-2研究仅纳入绝经后患者[4,5] （2）达尔西利 vs 瑞博西利：瑞博西利对CDK4的亲和力优于CDK6（选择性比约3.9），这可能与其致命性QTc延长的靶向性（CDK4在心肌细胞中的高表达）有关。达尔西利的CDK4/CDK6选择性比值接近1:1，QTc延长风险显著低于瑞博西利[8] （3）达尔西利 vs 阿贝西利：阿贝西利对CDK9的IC50（~57 nM）较低，体现了部分CDK9抑制活性，这被认为是其胃肠道毒性（特别是腹泻）较高的原因之一。达尔西利对CDK9的IC50 >1000 nM，胃肠道毒性明显低于阿贝西利[3] 4.2 CDK家族成员及其功能分布 CDK亚型结合的Cyclin 主要功能期主要生物学功能主要分布组织 CDK1 Cyclin B G2/M 有丝分裂启动泛表达于所有增殖细胞 CDK2 Cyclin E/A G1/S, S G1/S转换；DNA复制起始泛表达；在肠上皮、毛囊、骨髓高表达 CDK3 Cyclin C G0/G1 G0期退出表达受限，功能未完全阐明CDK4Cyclin D1/D2/D3G1pRb磷酸化启动；R点转换泛表达；乳腺上皮细胞高表达 CDK5 p35/p39 非细胞周期神经发育、神经元迁移中枢神经系统高表达CDK6Cyclin D1/D2/D3G1pRb磷酸化；造血干细胞增殖泛表达；造血细胞高表达 CDK7 Cyclin H 全周期 CAK活性（磷酸化其他CDK）；TFIIH复合物组分（转录起始）泛表达 CDK8 Cyclin C 全周期转录调控（Mediator复合物）泛表达 CDK9 Cyclin T/K 全周期转录延伸（P-TEFb复合物核心组分）泛表达核心关注点： CDK4和CDK6在功能上高度冗余——两者均可结合Cyclin D并磷酸化pRb。然而，组织特异性敲除实验揭示了一个重要差异：CDK6是造血干细胞增殖的主要驱动因子，而CDK4在内分泌敏感组织（如乳腺上皮）中的作用更为突出。这解释了为什么CDK4/6抑制剂的主要剂量限制性毒性（DLT）是骨髓抑制（中性粒细胞减少），而非其他组织毒性[12,13]。 4.3 对各器官系统的药理作用分述 4.3.1 对骨髓造血系统的作用机制链路： - CDK4/6抑制剂 → 阻断造血干细胞和粒细胞前体中Cyclin D-CDK4/6的活性 → 抑制pRb磷酸化 → G1期阻滞 → 粒细胞前体增殖抑制 → 循环中性粒细胞数量减少效应特征： - 靶点：主要影响CDK6依赖性的髓系祖细胞增殖 - 动力学特征：给药后7-10天出现中性粒细胞计数最低值（nadir），停药后7-14天内可恢复。这种可逆性是CDK4/6抑制剂区别于化疗（如烷化剂、蒽环类药物）导致不可逆骨髓损伤的关键特点[2,8] - 剂量-效应关系：中性粒细胞减少的发生率和严重程度呈剂量依赖性。150 mg/d时≥3级中性粒细胞减少症发生率约53%（DAWNA-1研究）[4] - 临床意义：这是所有CDK4/6抑制剂共有的"预期内（on-target）"药理学效应，也是DLT。但不同于化疗，CDK4/6抑制剂导致的中性粒细胞减少不伴有黏膜炎、发热风险相对较低（粒缺性发热率<2%），机制上可能因为保留了向炎症部位迁移的中性粒细胞功能[13] 4.3.2 对乳腺/内分泌敏感组织的作用机制链路： - CDK4/6抑制剂 → 阻断ER信号驱动的Cyclin D1转录上调 → 抑制Cyclin D1-CDK4复合物的组装 → 阻断pRb磷酸化 → 抑制ER+乳腺癌细胞增殖 - 协同机制：芳香化酶抑制剂（来曲唑）降低雌激素水平→减少Cyclin D1转录；CDK4/6抑制剂阻断Cyclin D1的下游效应→"上下游双重阻断" 关键药理学特点： - ER+乳腺癌细胞对CDK4/6抑制剂具有敏感性依赖——ER信号驱动Cyclin D1表达是此类肿瘤的"驱动依赖性（oncogene addiction）"表现之一 - 临床前模型中，达尔西利联合氟维司群可使MCF-7异种移植物实现接近完全的肿瘤生长停滞（TGI > 90%），单药则约为TGI 60%[2] - 耐药机制警示：长期CDK4/6抑制剂选择压力下，CCNE1扩增或CDK2过表达可绕过CDK4/6需求而驱动增殖[12] 4.3.3 对肝脏的作用与其他CDK4/6抑制剂不同，达尔西利的肝功能影响较小： - DAWNA-1研究中，达尔西利组ALT/AST升高（≥3级）发生率仅为1%-2%，显著低于瑞博西利的肝毒性发生率（约5%-10%）[4,8] - 机制推测：达尔西利的代谢产物对肝细胞的直接毒性较弱，且其CYP3A4代谢不产生已知的线粒体毒性代谢物 - 临床意义：合并脂肪肝或轻度肝功能不全（Child-Pugh A级）的患者可相对安全使用，但仍需定期监测肝功能 4.3.4 对胃肠道的作用 - 达尔西利组腹泻发生率约18%-25%，以1-2级为主（≥3级<1%），显著低于阿贝西利（腹泻总发生率约81%-90%，≥3级约10%-13%）[4,5,8] - 机制：阿贝西利的腹泻与CDK9抑制导致的肠上皮细胞凋亡增加及肠蠕动加速有关；达尔西利对CDK9亲和力极低（>1000 nM），因此胃肠道安全性更优[3] 4.3.5 对皮肤和附属器的作用 - 皮疹：约5%-10%，多数为1级 - 脱发：CDK4/6抑制剂共有的效应，因毛囊基质细胞的增殖需要CDK4/6活性。发生率约10%-15%，远低于化疗脱发 - 口腔黏膜炎：约5%-8%，1-2级为主 4.3.6 对心血管系统的作用 - QTc延长：显著低于瑞博西利。DAWNA-1研究中未报告≥3级QTc延长[4] - 高血压：约2.5%（1期研究数据），多为1-2级[2] - 机制：达尔西利对心肌细胞CDK4的抑制较弱，且对hERG钾通道无明显直接阻断作用五、临床适应症适应症总览序号适应症重要性获批状态 1 HR+/HER2-晚期乳腺癌——联合氟维司群（既往内分泌治疗进展后） ⭐⭐⭐ NMPA完全批准（2023.6） 2 HR+/HER2-晚期乳腺癌——联合来曲唑（一线，绝经后或联合OFS） ⭐⭐⭐ NMPA完全批准（2023.6） 3 HR+/HER2-晚期乳腺癌——联合芳香化酶抑制剂或氟维司群（一线/二线） ⭐⭐ CSCO指南推荐（2023版）适应症一：联合氟维司群用于既往内分泌治疗进展后的HR+/HER2-晚期乳腺癌 ⭐⭐⭐ 适用疾病： HR阳性、HER2阴性的局部晚期或转移性乳腺癌，既往接受过内分泌治疗（包括辅助内分泌治疗期间或结束后12个月内复发，或晚期一线内分泌治疗进展后）推荐剂量：达尔西利 150 mg，每日一次，口服，服药21天，停药7天（28天为一个周期）；联合氟维司群 500 mg 肌肉注射（第1周期的第1天和第15天各一次，此后每28天一次）循证依据： DAWNA-1研究（NCT03927456）——一项多中心、随机、双盲、安慰剂对照的III期临床试验[4]： - 纳入361例既往内分泌治疗进展的HR+/HER2-晚期乳腺癌中国患者 - 按2:1随机分组至达尔西利+氟维司群组 vs 安慰剂+氟维司群组 - 主要终点结果： - 研究者评估的mPFS：15.7个月 vs 7.2个月（HR=0.42, 95% CI: 0.31-0.58, p<0.0001） - 独立评审委员会（IRC）评估的mPFS：未达到 vs 11.0个月（HR=0.39） - ORR（客观缓解率）：在可测量病灶患者中，达尔西利组27.0% vs 安慰剂组11.9% - 临床获益率（CBR）：达尔西利组61.1% vs 安慰剂组39.8% - 结论：达尔西利联合氟维司群显著改善了PFS，安全性可接受[4] 指南推荐： - CSCO乳腺癌诊疗指南（2023版）：达尔西利联合氟维司群推荐用于内分泌治疗进展后的HR+/HER2-晚期乳腺癌（I级推荐，1A类证据） - 《CDK4/6抑制剂临床应用专家共识》（2023版）：明确推荐[9] 适应症二：联合来曲唑用于HR+/HER2-晚期乳腺癌一线治疗 ⭐⭐⭐ 适用疾病： HR阳性、HER2阴性的局部晚期或转移性乳腺癌，既往未在晚期阶段接受过全身治疗；包括绝经后患者，以及接受卵巢功能抑制（OFS）的绝经前/围绝经期患者推荐剂量：达尔西利 150 mg，每日一次，口服，服药21天，停药7天（28天为一个周期）；联合来曲唑 2.5 mg，每日一次口服（连续给药）循证依据： DAWNA-2研究（NCT03966898）——一项多中心、随机、双盲、安慰剂对照的III期临床试验[5]： - 纳入456例既往未在晚期阶段接受全身治疗的HR+/HER2-晚期乳腺癌患者（允许绝经前患者入组，并接受OFS） - 按2:1随机分组至达尔西利+来曲唑组 vs 安慰剂+来曲唑组 - 主要终点结果： - 研究者评估的mPFS：30.6个月 vs 18.2个月（HR=0.51, 95% CI: 0.38-0.69, p<0.0001） - 亚组分析关键发现： - 绝经后亚组HR=0.48（95% CI: 0.33-0.70） - 绝经前/围绝经期+OFS亚组HR=0.53（95% CI: 0.33-0.85）——首次证实国产CDK4/6抑制剂在绝经前人群中的疗效 - OS数据（期中分析）： HR=0.72（95% CI: 0.50-1.03），虽然未达到统计学显著性阈值，但显示明确获益趋势[5] - 结论：达尔西利联合来曲唑显著改善了一线治疗的PFS，且对绝经前患者同样有效[5] 指南推荐： - CSCO乳腺癌诊疗指南（2023版）：达尔西利联合内分泌治疗推荐用于HR+/HER2-晚期乳腺癌一线治疗（I级推荐） - NCCN Guidelines Breast Cancer (Version 4.2023)：CDK4/6抑制剂联合AI推荐为HR+/HER2-晚期乳腺癌的一线优选方案特别提示——绝经前患者（DAWNA-2的独特价值）： DAWNA-2是唯一纳入并验证了绝经前/围绝经期HR+/HER2-晚期乳腺癌患者的大型III期CDK4/6抑制剂临床研究之一。联合OFS（GnRH激动剂戈舍瑞林）后，达尔西利在该人群中的获益程度与绝经后患者一致。这对中国临床实践尤为重要：中国乳腺癌患者中绝经前患者占比高达约50%-60%，远高于西方国家（约25%），使得DAWNA-2的绝经前亚组数据具有重要的本土指导价值[5,9]。治疗目标（一线治疗）： 1. 最大化无进展生存期（PFS），延缓化疗启动时间 2. 维持或改善生活质量 3. 确保治疗的长期耐受性和依从性识别标准： - 确诊为HR+/HER2-的局部晚期（无法手术切除的III期）或转移性（IV期）乳腺癌 - 既往未在晚期阶段接受过系统性抗肿瘤治疗 - ECOG PS评分0-2 - 有可测量病灶（RECIST 1.1标准）或仅有骨转移 - 无内脏危象（visceral crisis）治疗原则： - 一线优先：对于无内脏危象的HR+/HER2-晚期乳腺癌，CDK4/6抑制剂+内分泌治疗应作为一线优选，而非化疗 - 长期维持：一旦有效且耐受，应持续用药直至疾病进展或不可耐受毒性；不应过早停药 - 序贯策略：达尔西利进展后可考虑更换另一种CDK4/6抑制剂（基于PACE和MAINTAIN研究的"after CDK4/6i"策略），或转向化疗/ADC药物六、临床应用Tips（循证用药要点） Tip 1 | 中性粒细胞减少管理——不要按化疗思维"预防性升白" 最常见误区：见到中性粒细胞减少即停用达尔西利，或者"预防性"使用G-CSF（粒细胞集落刺激因子）。正确做法： - 达尔西利导致的骨髓抑制是CDK4/6抑制的可逆性药理学效应，不同于化疗的细胞毒效应。G-CSF理论上可通过Cyclin D-CDK4/6非依赖的JAK-STAT通路刺激粒系增殖，但临床实践中不推荐常规预防性使用G-CSF，因为：（1）粒缺性发热（febrile neutropenia）发生率极低（<2%）；（2）G-CSF可能通过刺激骨髓前体细胞增殖而削弱CDK4/6抑制剂的抗肿瘤效应（"骨髓被盗论"的理论关注） - 中性粒细胞计数 ≥1.0×10⁹/L：无需调整剂量 - 中性粒细胞计数 0.5-1.0×10⁹/L：不调整剂量，每周监测血常规 - 中性粒细胞计数 <0.5×10⁹/L（伴或不伴发热）：暂停达尔西利，待恢复至≥1.0×10⁹/L后，以原剂量或降低一个剂量水平（125 mg）恢复治疗[7] 依据：参照DAWNA-1和DAWNA-2的方案规定以及CSCO乳腺癌诊疗指南中的CDK4/6抑制剂管理建议[4,5,9]。 Tip 2 | 肝功能异常患者的剂量选择——达尔西利的差异化优势常见误区：所有CDK4/6抑制剂都"一样伤肝"，肝功能异常一律禁用。正确做法： - 达尔西利在DAWNA-1中≥3级ALT/AST升高发生率仅1%-2%，是所有已获批CDK4/6抑制剂中肝毒性最低的之一[4] - 轻度肝功能不全（Child-Pugh A级）患者：无需调整达尔西利起始剂量（150 mg/d） - 中度肝功能不全（Child-Pugh B级）：建议从125 mg起始 - 重度肝功能不全（Child-Pugh C级）：尚未研究，不推荐使用 - 合并脂肪肝且肝功能正常或轻度异常的患者：可常规使用，每周期监测肝功能 - 若ALT/AST升高至>3×ULN：暂停给药，待恢复至≤3×ULN后以原剂量恢复（若首次发生）或降低一个剂量水平（若反复发生）[7,8] Tip 3 | CYP3A4药物相互作用管理——记住"清单思维" 常见误区：只关注说明书列出的个别药物，忽略临床常用药物的CYP3A4作用。必须熟记的CYP3A4药物清单：药物类型 CYP3A4强抑制剂（升高达尔西利AUC，需避免联用或降低剂量） CYP3A4强诱导剂（降低达尔西利AUC，应避免联用）抗真菌药酮康唑、伊曲康唑、伏立康唑、泊沙康唑 — 大环内酯类抗生素克拉霉素、泰利霉素 — 抗HIV药利托那韦、考比司他、茚地那韦依法韦仑、依曲韦林抗癫痫药 — 苯妥英、卡马西平、苯巴比妥抗结核药 — 利福平、利福布汀其他葡萄柚（含呋喃香豆素类化合物）、奈法唑酮圣约翰草（贯叶连翘）、恩杂鲁胺中药部分含呋喃香豆素的中药复方贯叶连翘提取物剂量调整原则： - 必须联用CYP3A4强抑制剂时：达尔西利减量至75 mg/d - 必须联用CYP3A4中度抑制剂时：达尔西利减量至125 mg/d - CYP3A4强诱导剂：避免联用（可能使达尔西利AUC降低>80%）[7,8] 一个容易忽略的细节：葡萄柚（西柚）及其果汁中的呋喃香豆素类成分可不可逆抑制肠道CYP3A4，显著增加达尔西利的口服生物利用度。应告知患者服药期间禁止食用葡萄柚及含葡萄柚成分的食物。 Tip 4 | 伴有骨转移患者——达尔西利联合方案不牺牲骨骼健康临床要点： - 氟维司群本身对骨代谢有潜在不利影响（雌激素降解），达尔西利对其无额外增加 - DAWNA-1和DAWNA-2中均允许使用骨改良药物（如唑来膦酸、地舒单抗），且不影响疗效评估 - 实际操作建议：伴有骨转移的患者，在CDK4/6抑制剂+内分泌治疗的同时，应常规给予骨改良药物预防骨相关事件（SREs）；骨改良药物不与达尔西利产生CYP3A4水平的有临床意义的相互作用 - 其他药物如NSAIDs用于骨痛对尿酸的排泄影响不大，可常规使用 Tip 5 | 患者依从性管理——21/7方案的沟通技巧实际问题： "服3停1"的给药方案对患者的记忆力要求较高，容易出现减量遗忘或在停药的7天内误服。解决方案： - 利用28天周期恰好接近一个月的特性，建议患者在日历上圈出每周期第22-28天作为停药日 - 使用药盒：21个"编号"格+7个"停用"标记格（空白格保持视觉提示） - 沟通话术： "不是吃28天停7天，是吃21天停7天——请记住'吃21'这个数字" - 强调每日固定时间服药（建议早餐后），若漏服且距离下一次服药时间不足12小时，则跳过该次漏服剂量 Tip 6 | 达尔西利 vs 哌柏西利——临床选择中的决策要素比较维度达尔西利哌柏西利数据来源 DAWNA-1/2（全中国人群） PALOMA-1/2/3（主要西方人群）一线mPFS 30.6个月（DAWNA-2） 24.8个月（PALOMA-2）绝经前数据 DAWNA-2亚组（有） PALOMA系列（无）肝功能影响轻微（≥3级ALT升高~1-2%）轻微中国患者可及性国产，医保覆盖好原研进口或仿制费用较低仿制药价格下降但仍高于国产指引：在中国患者中，达尔西利的数据来自中国本土III期研究，更贴近中国患者的病理特征和诊疗实践。对于绝经前患者，DAWNA-2是目前唯一提供高质量循证证据支持CDK4/6抑制剂一线使用的临床研究之一[5]。 Tip 7 | 老年人用药——免剂量调整的循证支持临床要点： - 达尔西利在≥65岁老年患者中的药代动力学参数（AUC, Cmax）与<65岁患者无显著差异 - DAWNA-1和DAWNA-2均纳入适量老年患者（65-75岁约15%-20%），安全性数据与整体人群一致 - 实际操作： ≥65岁HR+/HER2-晚期乳腺癌患者，若肝肾功能正常，无需调整达尔西利起始剂量（150 mg/d） - 合并中度肾功能不全（CrCl 30-59 mL/min）者，因达尔西利肾排泄占比低（约20%），通常无需调整剂量，但应加强毒性监测 - 合并重度肾功能不全（CrCl <30 mL/min）患者的药代动力学数据有限，建议从125 mg/d起始 Tip 8 | 达尔西利治疗中的影像学评估节奏实用建议： - 治疗前基线影像学评估（CT/MRI，含骨扫描或PET-CT）作为比较基准 - 首次疗效评估：第2周期结束后（第56天），此后每2-3个周期评估一次 - 特别注意：达尔西利可能出现初始的"肿瘤闪烁（tumor flare）"——服药早期骨扫描显示代谢增高，实为骨修复反应而非真正进展。结合CT骨窗双向评估，孤立性骨扫描异常需排除假性进展 - RECIST 1.1标准仍为金标准，但骨转移评估应结合临床症状、肿瘤标志物和影像学的综合判断七、不良反应与禁忌症 7.1 常见不良反应系统/器官不良反应发生率（DAWNA-1/DAWNA-2汇总）发生机制血液系统中性粒细胞减少 ≥3级：53%（任何级别约78%） CDK6依赖性髓系祖细胞增殖抑制（on-target效应）血液系统白细胞减少 ≥3级：35%（任何级别约65%）同中性粒细胞减少的机制血液系统血小板减少 ≥3级：5%（任何级别约30%） CDK4/6在巨核细胞成熟中的作用，通常较轻且可逆血液系统贫血 ≥3级：2%（任何级别约45%）红细胞前体细胞受抑，程度较轻消化系统腹泻 ≥3级：<1%（任何级别约20%）与基线肠上皮细胞CDK4/6抑制有关；达尔西利对CDK9的低亲和力使其腹泻率远低于阿贝西利消化系统恶心 ≥3级：0%（任何级别约15%）非特异性胃肠反应肝脏 ALT/AST升高 ≥3级：1-2%（任何级别约15%）代谢产物对肝细胞的轻度应激反应；达尔西利是同类中肝毒性最低者之一皮肤皮疹 ≥3级：<1%（任何级别约5-10%）可能涉及免疫介导机制，非CDK靶点毒性，通常为轻度斑丘疹全身乏力/疲劳 ≥3级：2%（任何级别约25%）多因素（肿瘤负荷、贫血、营养不良等），非特异性口腔口腔黏膜炎 ≥3级：<1%（任何级别约5-8%）口腔黏膜基底细胞增殖抑制，较轻 7.2 中毒/过量表现目前达尔西利缺乏特异性解毒剂，临床过量数据有限。基于药理机制推测的过量表现： - 严重骨髓抑制：全血细胞减少（中性粒细胞、血小板、血红蛋白全面下降），粒细胞缺乏性发热风险增加 - 胃肠道毒性加重：难治性腹泻、大量体液丢失、电解质紊乱 - 肝功能损伤： ALT/AST显著升高（可>10×ULN），伴或不伴胆红素升高 - 疲劳加重：严重的乏力和活动受限处理原则： - 立即停药 - 对症支持治疗（G-CSF用于粒细胞缺乏、输血支持、止泻补液等） - 无特效拮抗剂 - 因其高血浆蛋白结合率（约97%），血液透析无法有效清除达尔西利 7.3 禁忌症绝对禁忌症疾病/状态禁忌原因对达尔西利或其任何辅料过敏过敏反应风险，已在少数患者中观察到超敏反应妊娠期基于作用机制，CDK4/6抑制可损害胚胎发育；动物生殖毒性研究尚未完全披露，但同类药物在动物中显示胚胎致死和致畸性哺乳期达尔西利及其代谢物是否分泌至人乳汁未知，但不能排除风险相对禁忌症疾病/状态禁忌原因重度肝功能不全（Child-Pugh C级）缺乏该人群安全性和有效性数据；肝毒性风险显著增加未控制的内脏危象（Visceral crisis）需要快速起效的化疗或靶向治疗；CDK4/6抑制剂起效相对较慢（通常6-8周显现影像学疗效）活动性炎症性肠病或未控制的慢性腹泻可能会加重腹泻症状八、剂量与用法速查表适应症给药途径成人剂量儿童剂量备注 HR+/HER2-晚期乳腺癌（联合氟维司群）口服达尔西利150 mg qd，服药21天停7天；氟维司群500 mg IM，第1周期D1和D15各一次，此后每28天一次不适用 DAWNA-1方案[4]；空腹或随餐均可 HR+/HER2-晚期乳腺癌（联合来曲唑，绝经后）口服达尔西利150 mg qd，服药21天停7天；来曲唑2.5 mg qd连续不适用 DAWNA-2方案[5]；绝经后患者 HR+/HER2-晚期乳腺癌（联合来曲唑+OFS，绝经前/围绝经期）口服达尔西利150 mg qd，服药21天停7天；来曲唑2.5 mg qd连续；戈舍瑞林3.6 mg SC，每28天一次（OFS）不适用 DAWNA-2绝经前亚组方案[5] 合并CYP3A4强抑制剂时剂量调整口服 75 mg qd，服药21天停7天不适用如联用酮康唑、克拉霉素等[7,8] 合并CYP3A4中度抑制剂时剂量调整口服 125 mg qd，服药21天停7天不适用如联用氟康唑、红霉素等首次出现≥3级中性粒细胞减少后恢复给药口服恢复至≥1.0×10⁹/L后，以原剂量（150 mg）或125 mg恢复不适用若反复发生则降至125 mg或100 mg[7] 剂量参考来源：以上剂量均参考NMPA批准的达尔西利（艾瑞康）药品说明书（2023版）以及DAWNA-1/DAWNA-2研究方案中的剂量规定[4,5,7]。特殊说明： - 达尔西利目前仅适用于成人（≥18岁）乳腺癌患者，儿童及青少年中的安全性和有效性尚未建立 - 老年人（≥65岁）无需常规剂量调整 - 每周期开始前（第1天和第15天）应检测血常规 - 若多周期后仍维持良好耐受性，不建议擅自降低剂量——持续足量用药与预后改善相关九、药学考点速记 9.1 核心考点梳理考点关键内容常见题型 CDK4/6抑制剂的分子机制 ATP竞争性抑制CDK4/6 → 抑制pRb磷酸化 → E2F释放受阻 → G1期阻滞简答题/机制题达尔西利的来源和地位恒瑞自主研发，国产首个CDK4/6抑制剂；2021年NMPA有条件批准上市，2023年完全批准填空题/选择题 CDK4 vs CDK6的功能差异 CDK4在乳腺上皮高表达（内分泌敏感），CDK6在造血干细胞高表达（骨髓毒性靶点）选择题/鉴别题 DAWNA-1研究核心数据和意义达尔西利+氟维司群 vs 氟维司群；mPFS 15.7 vs 7.2个月；HR=0.42；覆盖二线及以上选择题/案例分析题 DAWNA-2研究核心数据和意义达尔西利+来曲唑 vs 来曲唑；mPFS 30.6 vs 18.2个月；HR=0.51；含绝经前亚组选择题/案例分析题达尔西利半衰期约44小时（t½ ~44h），支持每日一次给药方案选择题 CYP3A4药物相互作用强抑制剂酮康唑（减至75 mg/d）；强诱导剂利福平（避免联用）；葡萄柚禁止同服选择题/用药教育题达尔西利vs阿贝西利的毒性差异阿贝西利腹泻率高达81-90%（CDK9靶点毒性），达尔西利腹泻率约20% 比较题/选择题达尔西利的剂量限制性毒性（DLT）中性粒细胞减少（可逆性、on-target）选择题/简答题 CDK4/6抑制剂的耐药机制 CCNE1扩增、CDK2活化、Rb缺失、PI3K通路激活进阶简答题达尔西利vs瑞博西利心血管安全性瑞博西利可致临床意义QTc延长，达尔西利QTc影响轻微选择题/比较题 "服21停7"方案的设计原理骨髓前体细胞在停药7天内恢复增殖，以恢复中性粒细胞计数；兼顾疗效与安全性简答题/设计原理题 9.2 记忆口诀《达尔西利药理学歌诀》 CDK四六是开关，竞争结合堵门口 Rb不磷酸不能放，E2F困在胞浆游周期阻断G1处，乳腺肿瘤不乱走中国首个国产造，恒瑞研发品牌优四十四时半衰长，每天一次记心头吃三周来停一七，粒缺可逆不算忧酮康拉唑强抑酶，七十五毫克安全留利福平等莫碰它，葡萄柚果嘴别勾 DAWNA研究双星耀，一线二线月数久氟维司群来曲唑，联合内分泌稳守口诀解析： - 前四句：CDK4/6是细胞周期的关键开关，达尔西利竞争性结合ATP位点阻止底物结合，抑制Rb磷酸化使E2F不能释放入核，最终导致G1期阻滞 - "中国首个国产造"：达尔西利是中国首个获批的国产原研CDK4/6抑制剂，恒瑞医药研发 - "四十四时半衰长"：t½约为44小时，支持qd给药方案 - "服21停7"：21/28天方案 - "酮康拉唑强抑酶"：酮康唑等CYP3A4强抑制剂联用时需减量至75 mg/d - "葡萄柚果"：葡萄柚中含有呋喃香豆素抑制CYP3A4，服药期间禁食 - "DaWNA研究双星耀"：DAWNA-1研究和DAWNA-2研究是关键的III期临床试验 9.3 中毒解救要点问题对策严重中性粒细胞减少（<0.5×10⁹/L） ①暂停达尔西利；②可考虑G-CSF（非强制性，临床视发热/感染风险决定）；③恢复至≥1.0×10⁹/L后恢复给药≥3级腹泻 ①暂停达尔西利；②口服补液+止泻药（洛哌丁胺）；③恢复后以低一剂量水平恢复≥3级ALT/AST升高 ①暂停达尔西利；②排查其它肝损伤原因（病毒性肝炎、胆道梗阻、肝转移等）；③ALT/AST降至≤3×ULN后以原剂量或125 mg恢复严重药物相互作用（过量暴露） ①立即停药；②支持治疗；③血液透析无效（高蛋白结合率）；④无特异性拮抗剂十、参考文献中国指南/专家共识 [1] 国家药品监督管理局（NMPA）. 达尔西利片（艾瑞康）药品注册批准信息. 2021年12月（附条件批准）；2023年6月（完全批准）. [9] 国家肿瘤质控中心乳腺癌专家委员会, 中国抗癌协会肿瘤药物临床研究专业委员会. CDK4/6抑制剂临床应用专家共识（2023版）. 中华肿瘤杂志, 2023; 45(12): 1003-1017. DOI: 10.3760/cma.j.cn112152-20230428-00188. PMID: 38110309. [10] 中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范（CBCS, 2023版）. 中国癌症杂志, 2023; 33(1): 1-97. III期关键临床试验 [4] Xu B, Zhang Q, Zhang P, et al. Dalpiciclib plus fulvestrant in HR+/HER2− advanced breast cancer: a randomized, double-blind, phase 3 trial (DAWNA-1). *Nat Med*. 2021; 27(11): 1971-1979. DOI: 10.1038/s41591-021-01547-0. PMID: 34750551. [5] Zhang P, Zhang Q, Tong Z, et al. Dalpiciclib plus letrozole or anastrozole as first-line treatment for HR+/HER2− advanced breast cancer (DAWNA-2): a randomized, double-blind, phase 3 trial. *Lancet Oncol*. 2023; 24(6): 636-649. DOI: 10.1016/S1470-2045(23)00172-9. PMID: 37269844. 早期临床研究 [2] Zhang P, Xu B, Gui L, et al. A phase 1 study of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor in Chinese patients with advanced breast cancer. *Biomark Res*. 2021; 9(1): 24. DOI: 10.1186/s40364-021-00271-2. PMID: 33845905. 综述与药理机制文献 [3] Chen Z, et al. Advancements in Dalpiciclib for the Treatment of Breast Cancer Patients: A Review. *Breast Cancer (Dove Med Press)*. 2025; 17: 557-565. DOI: 10.2147/BCTT.S529794. PMID: 40620909. [11] O'Leary B, Finn RS, Turner NC. Treating cancer with selective CDK4/6 inhibitors. *Nat Rev Clin Oncol*. 2016; 13(7): 417-430. DOI: 10.1038/nrclinonc.2016.26. PMID: 27030077. [12] Dean JL, Thangavel C, McClendon AK, Reed CA, Knudsen ES. Therapeutic CDK4/6 inhibition in breast cancer: key mechanisms of response and failure. *Oncogene*. 2010; 29(28): 4018-4032. DOI: 10.1038/onc.2010.154. PMID: 20473330. 专业教材与参考书 [6] DrugBank Accession Number DB15897 — Dalpiciclib. Available at: https://go.drugbank.com/drugs/DB15897. [7] 江苏恒瑞医药股份有限公司. 达尔西利片（艾瑞康®）说明书. NMPA核准日期：2023年6月完整批准版. [8] U.S. National Library of Medicine. Dalpiciclib — Drug Information. PubChem Database. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Dalpiciclib. 基础细胞周期教材参考 [13] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. *Cell*. 2011; 144(5): 646-674. DOI: 10.1016/j.cell.2011.02.013. PMID: 21376230. 我药说说 · 让每一个药学人都能找到成长的方向关注我药说说，获取更多医药行业深度解读免责声明：本文仅供药学/医学教学参考，不构成临床用药建议。临床用药请以NMPA批准的药品说明书和相关临床诊疗指南为最终依据。

2026-06-04

·深度研选

Nat Rev Bioeng - 类器官：感染性疾病研究的新利器

这篇文章跟代谢关系不大，纯是笔者夹带私活，在求学阶段接触过，于是借此机会学习一下。标题：类器官作为感染性疾病研究平台一句话摘要：本综述系统梳理人类类器官在呼吸、消化、神经、心血管等多器官感染建模中的应用，并展望免疫化/血管化类器官、芯片类器官与AI融合对疫苗、药物研发及大流行病防范的变革潜力。发表期刊：Nature Reviews Bioengineering发表单位：伊拉斯姆斯大学医学中心（荷兰），香港大学，中国科学院等发表时间：2026/05第一作者：Kuan Liu 第一通讯： Qiuwei Pan 🔬 研究背景与意义感染性疾病持续威胁全球公共卫生，病毒、细菌、真菌和寄生虫均可引发地方性流行或突发疫情。传统研究依赖永生化细胞系和动物模型，但前者存在染色体不稳定、天然免疫缺陷等问题，后者则面临物种壁垒和伦理争议，均难以完整复现人类感染病理生理过程。类器官（organoid）——源自成体干细胞（ASC）、胎儿干细胞（FSC）或多能干细胞（PS细胞）的三维自组织结构——正在填补这一空白，为器官特异性感染研究提供了前所未有的生理相关模型。 Figure 1：不同类器官感染病原体的实验流程示意图 A：气道类器官模拟SARS-CoV-2感染——将原代人气道组织消化为单细胞，接种于Transwell膜，气液界面（ALI）培养2-4周后分化为假复层上皮，再接种SARS-CoV-2颗粒。B：胃类器官模拟幽门螺杆菌（H. pylori）感染——通过显微注射将细菌注入胃类器官管腔，或将类器官铺展为单层以实现顶端面直接暴露。C：胎儿肝来源肝细胞类器官模拟恶性疟原虫（P. falciparum）感染——机械解离后铺展为2D单层，接种疟原虫子孢子，支持肝内期发育。D：皮肤类器官模拟猴痘病毒（MPXV）感染——iPSC来源皮肤类器官培养75-90天后切块并建立ALI培养体系，顶端接种MPXV。E：巨噬细胞整合胆管细胞类器官模拟戊型肝炎病毒（HEV）感染——HEV感染24小时后整合巨噬细胞，建立免疫功能化类器官。F：滋养层类器官微流控芯片模拟寨卡病毒（ZIKV）感染——将含血管内皮层的芯片与滋养层类器官整合，研究垂直传播屏障及干扰素信号上调机制。 🩸 多器官感染建模：从呼吸道到淋巴系统气道类器官在新冠病毒（SARS-CoV-2）研究中发挥了核心作用：鼻类器官成功复现奥密克戎变异株高传播力，证实纤毛细胞和II型肺泡细胞是病毒主要靶细胞，而复合肺类器官揭示近端上皮细胞维持病毒复制、远端肺泡区域驱动超炎症反应的独特分工。此外，鼻、支气管、肺泡类器官还被用于研究RSV、流感病毒、MERS-CoV和人鼻病毒C型（HRV-C）等病原体——尤其是HRV-C此前因无法在永生化细胞系中复制而长期无法培养，类器官首次实现其连续传代。消化系统方面，胃类器官揭示了幽门螺杆菌对腺细胞（gland cells）比小凹细胞（pit cells）产生更强NF-κB炎症应答的细胞型别差异；肠道类器官首次实现人类诺如病毒的体外培养，并证实轮状病毒、星状病毒、沙门菌、艰难梭菌及隐孢子虫等多种肠道病原体的感染建模。肝脏类器官支持HBV完整病毒生命周期的重现（含cccDNA形成），以及疟原虫肝内期发育的可视化研究。神经系统方面，ZIKV感染脑类器官可复现小头畸形样表型，CMV感染可导致皮质结构紊乱，HSV-1感染暴露了单纯疱疹脑炎中干扰素亚型的神经保护机制——单独使用阿昔洛韦虽能终止病毒复制但无法阻止神经上皮损伤，联合抗炎治疗才能提供完整保护。 Table 1：各器官系统类器官感染建模汇总表涵盖呼吸系统、消化系统（胃/肠/胰/肝）、神经系统、心血管系统、皮肤、泌尿系统、生殖系统（子宫内膜/宫颈/滋养层）和淋巴系统，列出每类类器官的干细胞来源（PS细胞/ASC/FSC）、已建模病原体、技术优势、现有局限与未来方向。 ⚙️ 功能化类器官：免疫整合与血管化标准类器官缺乏免疫系统，限制了对复杂宿主-病原体互作的模拟。目前主流策略是将巨噬细胞等先天免疫细胞整合至上皮类器官，例如：肺类器官与巨噬细胞共培养用于结核分枝杆菌感染研究；含常驻巨噬细胞的肝/肠类器官可研究HEV+MPXV（肝）及轮状病毒+冠状病毒（肠）的免疫-病毒互作，并支持抗病毒与抗炎联合治疗策略的验证。脑类器官中整合小胶质细胞后，可分别复现HIV-1主要感染小胶质细胞的特征、风疹病毒感染的干扰素激活模式，以及SARS-CoV-2诱导的突触丢失，小胶质细胞还被证实对ZIKV脑损伤具有保护作用。 Figure 2：功能化类器官体系示意图 A：免疫功能化类器官——将巨噬细胞、中性粒细胞、NK细胞、树突细胞、T/B细胞等整合至多种组织类器官（肺、肝、肠、心、脑、胰腺），模拟天然免疫防御、炎症和适应性免疫应答。B：血管化类器官——整合PS细胞来源内皮细胞，构建血管网络，用于研究内皮感染、屏障破坏、病原体播散与免疫细胞募集。C：芯片类器官——将类器官与微流控平台结合，模拟肠道蠕动、心脏节律性跳动、大脑折叠结构等生理机械特征，并可构建多器官平台研究器官间病原体传播与免疫串扰。D：与基因编辑（CRISPR-Cas9）、单细胞/空间组学和人工智能（AI）的协同整合，支持病原体受体鉴定、宿主因子分析、感染模式识别和治疗效果预测。血管化是类器官功能化的另一核心挑战。血管类器官和血管化心脏类器官已用于SARS-CoV-2感染研究，脑皮质-血管组装体（assembloid）被应用于SARS-CoV-2相关神经炎症机制探索，而含HIV-1感染单核细胞跨内皮迁移功能的血管化脑类器官则为HIV相关神经病变提供了新型研究工具。血管网络不仅提供生理相关的病毒入侵途径，还能促进类器官成熟、支持组织稳态。 🚀 芯片类器官与多器官平台器官芯片（organ-on-a-chip）通过微流控技术为类器官提供动态生理条件，包括营养/氧气梯度、流体剪切力和周期性机械形变，从而模拟呼吸运动、肠蠕动、心脏节律和脑皱褶等生理特征。已建立的感染研究模型包括：含肺上皮-内皮-免疫细胞的人肺泡芯片（模拟SARS-CoV-2肺泡屏障损伤）、气道芯片（流感A+SARS-CoV-2双感染研究）、结肠类器官芯片（鉴定STEAP3为SARS-CoV-2肠道入侵宿主因子）以及含血管微环境的滋养层类器官芯片（证实血管化可上调干扰素信号、增强ZIKV抵抗力）。多器官平台将不同组织类器官置于独立腔室并以微流控通道相连，可模拟HEV的"肠-肝"传播轴、T细胞介导的抗丙型肝炎病毒免疫杀伤（T细胞-肝类器官共培养）以及流感疫苗诱导的淋巴滤泡生发中心反应。这些平台代表感染性疾病体外研究从单器官向系统整合迈进的重要一步。 💊 疫苗与药物研发应用人源淋巴样类器官（来自扁桃体、脾脏、淋巴结组织）可复现抗原特异性B细胞扩增和抗体应答，已被用于评估流感疫苗诱导的体液与细胞免疫应答，并鉴定了新型保护相关免疫指标（correlates of protection）。免疫功能化类器官则有望同步评估抗体中和、细胞毒性T细胞（CTL）杀伤和病毒感染抑制，实现疫苗效果的多维度评价。药物研发方面，脑类器官鉴定了ZIKV感染的小分子抑制剂，鼻类器官用于评估抗SARS-CoV-2单克隆抗体，肝类器官支持抗HEV药物筛选，原代肠道类器官实现了抗MPXV候选药物的可扩展筛选。整合AI驱动药物发现平台后，已成功识别抗逆转录病毒药物比替拉韦（bictegravir）和依曲韦林（etravirine）对猴痘病毒的抑制活性，大幅加速了老药新用的发现流程。 Figure 3：类器官用于疫苗评估和药物研发流程图 A：动物模型在疫苗研发中的局限（物种壁垒、低通量、伦理问题）。B：人源淋巴样类器官可重现疫苗诱导的个体间免疫应答差异，评估细胞因子分泌和中和抗体产生。C：免疫功能化类器官实现中和抗体、CTL杀伤和感染保护的联合评价。D：传统治疗研发管线（2D细胞+动物模型）。E：类器官平台支持小分子、中和抗体和基因编辑疗法的测试。F：大规模扩增培养（转瓶实现40倍扩增）结合AI和高内涵成像，推动规模化药物筛选。G：免疫功能化类器官评估抗感染药物、免疫调节剂和联合用药策略。 🌄 动物源性感染与大流行病防范蝙蝠是SARS-CoV、MERS-CoV、尼帕病毒等高危病毒的自然宿主，但此前缺乏可用的体外研究工具。近期建立的多物种蝙蝠类器官平台（涵盖5种食虫蝙蝠的气道、肺泡、肾脏和肠道类器官）揭示了SARS-CoV-2在不同蝙蝠种间肠道类器官中的受体限制性复制差异，MERS-CoV的复制谱系与二肽基肽酶-4（DPP4）受体表达水平相关，并首次从蝙蝠粪便中分离出2种此前未知的病毒。该平台还通过转录组学分析揭示了蝙蝠独特的干扰素免疫耐受机制，并支持瑞德西韦等抗病毒药物的2D单层测试。图 Figure 4：类器官用于研究人畜共患感染和大流行病防范的示意图 A：来自多种动物宿主的人畜共患病原体溢出事件示例（埃博拉、拉沙病毒、寨卡病毒、猪链球菌、汉坦病毒等）。B：多物种多器官类器官平台（啮齿类、蝙蝠、猪等）用于研究物种特异性和组织特异性宿主-病原体互作。C：类器官平台支持新发病原体的分离与扩增、病原体组织嗜性评估、单细胞基因组学分析和抗感染药物筛选。 💡 研究意义本综述全面梳理了类器官技术在感染性疾病研究中的应用图谱，揭示其从单器官感染建模到免疫功能化、血管化、多器官芯片整合的发展脉络，以及与CRISPR基因编辑、单细胞/空间组学和AI的深度融合趋势。类器官的核心价值在于：在传统细胞系无法复制病毒的场景中（如HRV-C、诺如病毒）实现突破性培养；在动物模型无法准确复现人类特异性病理的领域（如SARS-CoV-2奥密克戎、ZIKV小头畸形）填补空白；以及为个体化治疗评估和跨物种传播风险预测提供全新工具。面向未来，该领域需在五个维度取得突破：①将非病毒病原体（耐药菌、真菌）纳入类器官研究；②引入微生物组及免疫细胞提升生理复杂度；③标准化扩增与分化方案以改善可重复性；④整合前沿技术加速药物发现与风险评估；⑤提升可及性，通过开放技术、培训和低成本替代材料，使低中收入国家也能充分受益于类器官研究红利。一句话点评：从COVID-19到猴痘，类器官正在重塑感染性疾病研究的"人类生物学真相"——它不是动物模型的替代品，而是通往精准感染医学的新桥梁。原文一键下载链接如下： Organoidsasplatformsforinfectiousdiseaseresearch.pdf

100 项与依曲韦林相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D04112	依曲韦林	J05AG04	DB06414

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适应症	国家/地区	公司	日期
HIV感染	美国	Janssen Research & Development LLC	2008-01-18

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适应症	最高研发状态	国家/地区	公司	日期
怀孕	临床3期	美国	Janssen Scientific Affairs LLC	2009-04-09
获得性免疫缺陷综合征	临床2期	奥地利	Janssen-Cilag International NV	2009-06-01
获得性免疫缺陷综合征	临床2期	丹麦	Janssen-Cilag International NV	2009-06-01
获得性免疫缺陷综合征	临床2期	法国	Janssen-Cilag International NV	2009-06-01
获得性免疫缺陷综合征	临床2期	德国	Janssen-Cilag International NV	2009-06-01
获得性免疫缺陷综合征	临床2期	匈牙利	Janssen-Cilag International NV	2009-06-01
获得性免疫缺陷综合征	临床2期	以色列	Janssen-Cilag International NV	2009-06-01
获得性免疫缺陷综合征	临床2期	罗马尼亚	Janssen-Cilag International NV	2009-06-01
获得性免疫缺陷综合征	临床2期	俄罗斯	Janssen-Cilag International NV	2009-06-01
获得性免疫缺陷综合征	临床2期	西班牙	Janssen-Cilag International NV	2009-06-01

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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


NCT01641367 (ACTG A5288, Pubmed)	临床4期	三线	257	RAL	獵醖製網觸餘選積構範(鬱鏇遞製繭獵衊觸願壓) = 構夢製構簾築廠鏇繭餘構壓網淵鹽膚齋鏇鏇醖 (衊鹽齋遞積構選淵製鑰 ) 更多	-	2022-06-01
NCT01641367 (ACTG A5288, Pubmed)	临床4期	三线	257	DRV/r	積鏇顧範醖壓廠鹽積壓(繭鏇窪簾醖醖糧膚網鹹) = 築窪築鹹遞糧築製夢顧觸範淵糧蓋壓積襯範膚 (遞鹹淵齋壓窪築壓衊壓 )	-	2022-06-01
NCT00980538 (TMC125-TIDP35-C239, CTgov)	临床3期	HIV感染	180	Etravirine	構艱築選淵觸構繭廠壓 = 鑰鑰鏇鹹製網鹽窪鑰淵鹹醖簾窪構衊繭襯簾積 (鏇窪網構膚網顧壓艱顧, 範糧願鹹鹹蓋襯糧憲醖 ~ 繭選憲範衊憲鹹壓衊糧) 更多	-	2021-12-21
NCT01504841 (CTgov)	临床1/2期	HIV感染	26	Etravirine (ETR) (Cohort I: Treatment Experienced, 2 to 6 Years of Age)	窪壓製網鹹壓範鹹遞鑰(顧艱鹹鹽齋構範簾齋鹽) = 鹽製觸夢蓋膚齋製餘範壓鹹壓鏇願遞鏇壓鑰獵 (築簾齋醖積構憲網遞網, 3615.36) 更多	-	2019-09-17
NCT01504841 (CTgov)	临床1/2期	HIV感染	26	Etravirine (ETR) (Cohort II: Treatment Experienced, 1 to 2 Years of Age)	窪壓製網鹹壓範鹹遞鑰(顧艱鹹鹽齋構範簾齋鹽) = 構範淵襯憲膚範製餘窪壓鹹壓鏇願遞鏇壓鑰獵 (築簾齋醖積構憲網遞網, 3167.11) 更多	-	2019-09-17
NCT02212379 (ANRS 163 ETRAL, Pubmed \| J Antimicrob Chemother) 人工标引	临床2期	HIV感染	165	raltegravir+etravirine	鹹獵構淵選鏇艱憲範範(鬱積觸構壓範鏇餘艱淵) = 鹽選餘膚蓋齋夢艱壓獵繭鏇淵襯製憲獵壓積淵 (蓋願網構淵壓遞淵餘選, 95.6 ~ 99.9) 更多	积极	2019-09-01
NCT00855413 (CID 0821, CTgov)	临床4期	HIV感染	15	etravirine+Ritonavir+Darunavir	鑰鑰窪鹹糧蓋鏇選築鹹(淵衊繭繭夢夢遞鬱鑰遞) = 繭夢繭衊鬱壓願艱顧網鑰齋鏇膚鬱憲築糧觸鏇 (鑰膚膚艱鑰觸範範繭觸, 憲鏇齋繭繭醖選鹽蓋壓 ~ 蓋顧構窪醖遞醖繭蓋襯) 更多	-	2017-10-17
NCT00665847 (PIANO \| TMC125-TiDP35-C213, Pubmed \| Curr Opin Pulm Med \| Antivir Ther) 人工标引	临床2期	HIV感染	101	background regimen+etravirine	餘淵襯鏇顧衊鏇製鹽鑰(齋範淵夢壓積網簾蓋鬱) = 醖衊遞壓繭壓襯衊餘網衊醖夢糧願廠製選衊糧 (鑰壓遞獵齋築鏇獵窪艱 )	-	2016-01-01
NCT00959894 (Pubmed \| Curr Opin Pulm Med \| Antivir Ther) 人工标引	临床2期	HIV感染	79	emtricitabine+etravirine	顧壓壓窪蓋鏇製獵夢餘(範醖範醖衊製繭觸夢糧) = 簾觸積鑰鑰艱鹹餘窪繭廠壓鹽憲遞餘網築襯廠 (積壓觸廠襯壓醖積構鏇, 66 ~ 86) 更多	积极	2016-01-01
NCT00959894 (CTgov)	临床2期	HIV感染	80	Etravirine (Intelence)+Truvada	窪觸襯選構齋構鑰繭窪 = 觸壓蓋糧艱願願齋願餘齋構繭膚鹹網膚構蓋顧 (襯醖築網積夢獵鹽遞顧, 淵繭築構鏇窪鏇膚艱夢 ~ 範鬱簾淵蓋糧憲淵製選) 更多	-	2015-05-13
NCT01625169 (CTgov)	N/A	HIV感染	9	Etravirine pharmacokinetics in breast milk and plasma	範鏇襯齋觸夢糧鹽艱憲(醖構糧蓋遞選網衊遞齋) = 製遞繭積艱構製鏇積窪淵餘築觸選鹽繭艱襯鑰 (壓簾鬱齋艱遞淵簾艱願, 261.77) 更多	-	2014-08-07
NCT01422330 (TMC125IFD3002, Pubmed \| J Int AIDS Soc)	临床4期	HIV感染	211	Etravirine 200 mg bid	顧鹹衊範網蓋餘艱積齋(窪選顧夢鑰廠襯選醖鏇) = 範齋選膚鹹築積願襯築鏇遞膚鹹鏇蓋衊壓構鏇 (餘窪繭遞餘積齋遞願餘 ) 更多	-	2014-01-01