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更新于：2026-02-27
Exebacase
更新于：2026-02-27
概要
基本信息
非在研机构- |
权益机构- |
最高研发阶段临床3期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评突破性疗法 (美国) |
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结构/序列
Sequence Code 552628766
来源: *****
关联
4
项与 Exebacase 相关的临床试验NCT04160468
A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of a Single Dose of Exebacase in Patients Receiving Standard-of-Care Antibiotics for the Treatment of Staphylococcus Aureus Bloodstream Infections (Bacteremia), Including Right-Sided Infective Endocarditis
The purpose of this superiority study is to evaluate the efficacy and safety of exebacase in addition to standard of care antibiotics (SoCA) compared with SoCA alone for the treatment of patients with Staphylococcus aureus (S. aureus) bloodstream infections (BSI), including right-sided infective endocarditis (IE). Patients will be randomized to receive a single intravenous dose of exebacase or placebo. Patients will receive SoCA selected by the investigators based on the protocol.
Exebacase, a direct lytic agent, is an entirely new treatment modality against S. aureus. Exebacase is a recombinantly-produced, purified cell wall hydrolase enzyme that results in rapid bacteriolysis, potent biofilm eradication, synergy with antibiotics, low propensity for resistance, and the potential to suppress antibiotic resistance when used together with antibiotics. Exebacase represents a first-in-field, first-in-class treatment with the potential to improve clinical outcome when used in addition to SoCA to treat S. aureus BSI including IE.
Exebacase, a direct lytic agent, is an entirely new treatment modality against S. aureus. Exebacase is a recombinantly-produced, purified cell wall hydrolase enzyme that results in rapid bacteriolysis, potent biofilm eradication, synergy with antibiotics, low propensity for resistance, and the potential to suppress antibiotic resistance when used together with antibiotics. Exebacase represents a first-in-field, first-in-class treatment with the potential to improve clinical outcome when used in addition to SoCA to treat S. aureus BSI including IE.
开始日期2019-12-20 |
申办/合作机构 |
NCT03163446
A Multicenter, Double-Blind, Randomized, Comparative Study of the Safety, Tolerability, Efficacy, and Pharmacokinetics of CF-301 vs. Placebo in Addition to Standard-of-Care Antibacterial Therapy for the Treatment of Adult Patients With Staphylococcus Aureus Bloodstream Infections (Bacteremia) Including Endocarditis
The purpose of this study is to evaluate the safety, tolerability, efficacy and pharmacokinetics (PK) of CF-301 in addition to background standard of care (SOC) antibacterial therapy for the treatment of Staphylococcus aureus (S. aureus) bloodstream infections (bacteremia), including endocarditis in adults. Patients will be randomized to receive a single intravenous dose of CF-301 or placebo in addition to SOC antibacterial therapy. Patients will be prescribed standard of care antibiotics selected by the investigators based on their professional experience, practice guidelines and local antibiotic susceptibility information for the treatment of S. aureus bacteremia.
CF-301 is a lysin and member of a new class of targeted protein-based antimicrobials that has demonstrated activity against S. aureus in laboratory (in vitro) and animal studies, alone and in addition to conventional antibiotics.
CF-301 is a lysin and member of a new class of targeted protein-based antimicrobials that has demonstrated activity against S. aureus in laboratory (in vitro) and animal studies, alone and in addition to conventional antibiotics.
开始日期2017-05-23 |
申办/合作机构 |
NCT02439359
A Phase 1, Placebo-Controlled, Dose-Escalating Study to Examine the Safety and Tolerability of Single Intravenous Doses of CF-301 in Healthy Male and Female Subjects
A Phase 1, Placebo-Controlled, Dose-Escalating Study to Examine the Safety and Tolerability of Single Intravenous Doses of CF-301 in Healthy Subjects.
开始日期2015-05-01 |
申办/合作机构 |
100 项与 Exebacase 相关的临床结果
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100 项与 Exebacase 相关的转化医学
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100 项与 Exebacase 相关的专利（医药）
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18
项与 Exebacase 相关的文献（医药）2026-02-01·Expert Opinion on Drug Discovery
Advances in methicillin-resistant
Staphylococcus aureus
drug discovery: developments and challenges
Review
作者: Mylonakis, Eleftherios ; Vassilopoulos, Stephanos
INTRODUCTION:
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of severe infections with excess mortality. Progress with traditional antibiotics has been incremental, while resistance, persistence, tolerance, and biofilm formation continue to erode effectiveness. Parallel advances in small-molecule discovery, long-acting lipoglycopeptides, next-generation β-lactams, and non-traditional modalities such as bacteriophage lysins have renewed interest in expanding therapeutic options, though transition from promising preclinical signals to clinical benefit remains challenging.
AREAS COVERED:
A literature search was conducted using PubMed/MEDLINE, and Embase, for articles published from January 2010 through March 2025. This review synthesizes developments across: (i) agents in key clinical trials for invasive MRSA infection, emphasizing on trial designs, efficacy, and safety considerations; (ii) clinical study data with newer agents for MRSA skin infections and their potential application in invasive disease; (iii) preclinical pipelines including natural products, novel compounds, and other innovative antimicrobial strategies.
EXPERT OPINION:
Among investigated agents, ceftobiprole, ceftaroline, dalbavancin, and exebacase represent promising options for invasive MRSA infections. The pipeline is further strengthened by novel classes and antimicrobial peptides, which show anti-MRSA activity and a low risk for resistance in preclinical models. Continued multidisciplinary collaboration and robust clinical trial infrastructure are essential to translate these advances into improved patient outcomes.
2026-01-06·JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Article
作者: Schuch, Raymond ; Tolosana, José María ; Miró, José M ; Hernández-Meneses, Marta ; Krivak, Filip ; Cañas, María-Alexandra ; García-González, Javier ; Quintana, Eduard ; Moreno, Asunción ; García-De-La-Mària, Cristina ; Cuervo, Guillermo ; Sandoval, Elena ; Perissinotti, Andres ; Vidal, Barbara ; Falces, Carles ; Llopis, Jaume
Abstract:
Background:
Infective endocarditis (IE) is a severe infection mainly caused by Staphylococcus aureus, Enterococcus faecalis and viridans streptococci. Coagulase-negative staphylococci (CoNS), especially methicillin-resistant Staphylococcus epidermidis (MRSE), are major pathogens in prosthetic valves and devices. Exebacase is a first-in-class, antistaphylococcal lysin with rapid bactericidal and antibiofilm activity.
Objective:
To assess the in vitro activity of exebacase and standard IE antibiotics against S. aureus and CoNS isolates from IE patients in a university hospital (2010–2020).
Methods:
A total of 211 consecutive strains were analysed: S. aureus [n = 103 (82 MSSA, 21 MRSA)], S. epidermidis [n = 76 (20 MSSE, 56 MRSE)] and other CoNS species (n = 32, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Staphylococcus hominis, Staphylococcus capitis, Staphylococcus schleiferi, Staphylococcus caprae, Staphylococcus pasteuri). Broth microdilution MICs were determined for exebacase and comparators (cloxacillin, ceftaroline, vancomycin, daptomycin, gentamicin, rifampicin).
Results:
Exebacase inhibited all S. aureus at ≤1 mg/L. Geometric mean (GM) MICs were 0.56 mg/L for MSSA and 0.49 mg/L for MRSA, with MIC50/90 of 0.5/1 mg/L. For S. epidermidis, GM MICs were 3.03 mg/L (MSSE) and 3.40 mg/L (MRSE), with MIC50/90 of 4/16 and 4/8 mg/L, respectively. Other CoNS showed GM MICs ranging from 0.49 mg/L (S. capitis) to 2.59 mg/L (S. lugdunensis), with intermediate values for S. haemolyticus (1.15), S. hominis (1.0) and S. schleiferi (0.79). Exebacase activity was comparable to β-lactams, vancomycin and daptomycin and remained unaffected by resistance.
Conclusions:
Exebacase activity was independent of methicillin resistance and consistently higher against S. aureus than S. epidermidis. Further research is warranted to explore lysins in combination against staphylococcal infections.
2023-08-10·Microbiology spectrum
Rapid bacteriolysis of Staphylococcus aureus by lysin exebacase.
Article
作者: Vila-Farres, Xavier ; Swift, Steven ; DeJonge, Boudewijn ; Sauve, Karen ; Ambler, Jane E ; Oh, Jun ; Schuch, Raymond
Lysins (peptidoglycan hydrolases) are promising new protein-based antimicrobial candidates under development to address rising antibiotic resistance encountered among pathogenic bacteria. Exebacase is an antistaphylococcal lysin and the first member of the lysin class to have entered clinical trials in the United States. In this study, the bacteriolytic activity of exebacase was characterized with time-kill assays, turbidity reduction assays, and microscopy. Three methicillin-susceptible Staphylococcus aureus and three methicillin-resistant S. aureus isolates were tested in time-kill assays over a range of concentrations from 0.25 to 8 × MIC. Exebacase demonstrated a concentration-dependent killing and showed bactericidal activity (≥3 log10 kill achieved relative to the starting inoculum) within 3 h at 1 × MIC against all strains tested. Dose-dependent lysis by exebacase was, furthermore, observed in the turbidity reduction assay, wherein decreases in initial OD600 of 50% were observed within ~15 min at concentrations as low as 4 µg/mL. Membrane dissolution, loss of cytoplasmic material, and lysis were confirmed by video and electron microscopy. The demonstrated rapid bacteriolytic effect of exebacase is an important distinguishing feature of this novel modality. IMPORTANCE To guide the development of an investigational new antibacterial entity, microbiological data are required to evaluate the killing kinetics against target organism(s). Exebacase is a lysin (peptidoglycan hydrolase) that represents a novel antimicrobial modality based on degradation of the cell wall of Staphylococcus aureus. Killing by exebacase was determined in multiple assay formats including time-kill assays, wherein reductions of viability of ≥3 log10 colony-forming units/mL were observed within 3 h for multiple different isolates tested, consistent with very rapid bactericidal activity. Rapid reductions in optical density were likewise observed in exebacase-treated cultures, which were visually consistent with microscopic observations of rapid lysis. Overall, exebacase provides a novel antimicrobial modality against S. aureus, characterized by a rapid cidal and lytic activity.
48
项与 Exebacase 相关的新闻（医药）2026-02-06
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
临床结果临床1期
2026-02-03
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
临床结果临床1期
2025-11-12
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当前，抗菌药物耐药性(antimicrobial resistance, AMR)问题日益严峻，为全球卫生和社会经济带来了重大挑战，而新型抗菌药物研发管线的不足更加剧了细菌等微生物耐药危机。2019年，全球204个国家或地区共计约127万人死于细菌耐药[1]，到2050年预计将飙升至1000万人，累计经济损失预计高达100万亿美元[2]，但在2017-2020年间，仅11款抗菌新药上市[3]，且没有一款药物为窄谱抗菌药物。
广谱抗菌药物能够强效抑制大部分革兰阴性菌和革兰阳性菌，某些药物还能抑制支原体等其他病原微生物；窄谱抗菌药物则只能特异性杀灭某一种或一类细菌[4]。过去，临床和商业因素都极大地驱动了广谱抗菌药物的研发。虽然细菌培养与药敏试验有助于更好地选择敏感药物，但结果报告通常滞后于临床需求，因而临床医生常常倾向于经验性地选择广谱抗菌药物以尽可能覆盖病原菌[5]；广谱抗菌药物的选择偏好以及可用于肺炎、腹腔感染或尿路感染等广泛适应症所带来的巨大经济利益撬动了药企的资金投入，而窄谱抗菌药物在先导化合物发现与优化过程中却往往被放弃进一步研发[6]。
然而，广谱抗菌药物往往会对肠道菌群带来附加伤害，从而可能导致二重感染[7]，最严重的不良反应之一为艰难梭菌过度生长引起的伪膜性肠炎，死亡率超40%[8]；此外，广谱抗菌药物的使用还会加剧AMR的产生，广谱抗菌药物对于致病菌以外的其他细菌可能具有较弱的活性，在长期的亚抑制暴露水平下，这些细菌可能产生耐药性[9]。
有学者曾提出“STEDI”(谱/转移/支持/多样/保障，spectrum/transmission/enablement/diversity/insurance)原则[10]以全面评估抗菌药物的社会价值，指导新型抗菌药物的研发，其中“S”即代表开发窄谱抗菌药物，以降低对其他菌群的附加伤害和选择性压力。近年来，新型窄谱抗菌药物的研发正在逐渐增多，尤其是许多非传统产品[6]。本文对目前处于临床开发阶段的窄谱抗菌药物进行了梳理，尤其关注噬菌体、抗体药物等非传统产品的研发进展、目前面对的主要挑战和未来发展前景。1 临床研发中窄谱抗菌药物1.1 噬菌体疗法
噬菌体(bacteriophage，简称phage)于1915年首次被发现[11]，可感染细菌、真菌、螺旋体和支原体等，具有病毒的生物学特征，即个体微小、结构简单，只含有一种核酸(DNA或RNA)，只能在活细胞中以复制的方式增殖。噬菌体由头部和尾部组成，头部衣壳内含有噬菌体的遗传物质DNA或RNA，尾部含能够特异性识别宿主细胞表面受体的受体结合蛋白(receptor binding protein, RBP)，与噬菌体黏附有关[12]。根据能否裂解细菌，噬菌体可分为烈性噬菌体(溶菌型噬菌体)和温和噬菌体(溶原型噬菌体)两大类，前者能够在侵入宿主菌后不断增殖并使细菌裂解死亡(图1)，所以一般采用烈性噬菌体治疗细菌感染[13]，而且由于其增殖特性，烈性噬菌体天然成为一种可自我扩增的“药物”，这是传统抗菌药物不可能做到的。此外，由于噬菌体与细菌表面受体的分子结构存在互补性，所以还具有窄谱抗菌特性，能够特异性感染宿主菌，进而使其裂解死亡[14]。①噬菌体可通过其尾部的RBP黏附于细菌表面受体(如λ噬菌体特异性结合大肠埃希菌LamB受体)，产生酶裂解局部细胞壁，并将自身核酸(DNA或RNA)注入细菌；②利用细菌的氨基酸、核苷酸、能量和细胞器进行病毒自身核酸的复制和蛋白质外壳的合成；③组装成完整的子代噬菌体；④释放内溶素等酶破坏宿主菌细胞壁，使其裂解死亡，子代噬菌体释放到外界，继续感染新的宿主。
噬菌体疗法即为借助噬菌体裂解宿主菌的特性达到杀灭细菌的目的，从而治疗细菌感染。Félix d’Hérelle是开启噬菌体疗法的先驱，1919年，d’Hérelle从鸡粪中分离出噬菌体，成功治疗了一种鸡伤寒病[15]；之后，在自我给药证明口服噬菌体制剂的安全性后，他首次在人体使用噬菌体疗法成功治疗了3名志贺菌感染所致细菌性痢疾的患儿[16]。噬菌体疗法开始应用的时间远早于青霉素上市，但由于青霉素等药物的抗菌活性强，所以噬菌体疗法逐渐被放弃，仅在格鲁吉亚、波兰和俄罗斯等东欧国家继续使用。
21世纪以来，由于AMR日益泛滥和传统抗菌药物研发陷入困境，噬菌体疗法迎来新一轮临床关注，Petrovic Fabijan等详细梳理了噬菌体科学和噬菌体疗法发展的重要里程碑[17]，可供参考。此前许多同情用药的单一病例报告已证明了噬菌体疗法在广泛患者人群中的安全性[18]，如Maddocks等报道一位77岁女性在肺癌术后出现严重的呼吸机相关性肺炎，感染细菌为多重耐药铜绿假单胞菌，对包括美罗培南、亚胺培南、哌拉西林/他唑巴坦和环丙沙星等在内的多种抗菌药物产生耐药性，体外药敏实验结果显示AB-PA01(4种专性烈性噬菌体组成的混合物，每种噬菌体的浓度约为1×109，扩大使用计划经FDA批准)对该患者的分离株具有高度活性，在获得患者的知情同意后，于第23天开始为期7 d的噬菌体静脉注射和雾化吸入辅助治疗，在噬菌体治疗第4天，铜绿假单胞菌培养转阴，且在AB-PA01治疗完成后的6个月内一直保持阴性，此外，在治疗期间和随访过程中均未观察到不良事件[19]。
目前正积极开展临床试验以评估噬菌体疗法的有效性和安全性疗效，但尚无FDA或EMA批准上市的噬菌体产品。根据ClinicalTrials检索结果，截至2024年10月，有12款噬菌体产品处于临床研发阶段(表1)，与2020年(仅4款噬菌体产品)相比明显增加[6]。大多数产品处于I/Ⅱ期和II期临床试验(10/12，83%)，只有1款噬菌体裂解酶CF-301推进到了Ⅲ期临床试验(本综述主要关注噬菌体疗法，有关CF-301及该类药物的介绍可参考McCarthy等[20]和Murray等[21]报道)。
由于噬菌体的极端生物特异性，单一噬菌体难以解决临床实际中多种细菌感染的问题，故目前正在积极探索扩大噬菌体宿主谱的方法，根据研究进展，有以下4种方法：①将多种宿主范围不同的噬菌体组合成噬菌体“鸡尾酒”；②通过基因工程定向改造噬菌体宿主谱；③体外连续培养诱导噬菌体宿主范围发生改变；④从自然界中分离筛选宽谱噬菌体[22]。根据检索结果，目前临床管线中的噬菌体产品采用的是前两种方法：除YPT-01(单种噬菌体)和CF-301(噬菌体裂解酶)外，其余噬菌体产品均为噬菌体“鸡尾酒”。尤其值得注意的是，大多数产品使用的是野生型噬菌体，而LBP-EC01[23]和SNIPR001[24]均为基因工程噬菌体，均对噬菌体进行了CRISPR/Cas3增强。
CRISPR/Cas系统增强的基因工程噬菌体最早可追溯至2014年[25]，Bikard等将CRISPR/Cas9系统克隆至噬菌体ΦNM1z中，体外研究及小鼠皮肤感染模型中的研究发现，在特殊设计的CRISPR RNA(crRNA)引导下，Cas9能够特异性破坏金黄色葡萄菌中携带耐药基因的质粒，而对非靶向菌株的影响较小[25]。Choi等最近报告了一种高效的工程噬菌体改造工具，该团队通过将Cas9基因和λRed重组系统(包括Exo、Bet和Gam蛋白)整合到铜绿假单胞菌的染色体上，构建了生产者(producer, PD)细胞，当野生型噬菌体感染这些PD细胞后，Cas9会根据sgRNA的引导，靶向切割野生型噬菌体基因组中的特定序列，同时λRed系统利用同源重组机制，将编辑模板整合到切割位点，从而生成重组噬菌体，实现对噬菌体基因组的快速、精确编辑[26]。然而，目前处于临床试验阶段的工程噬菌体LBP-EC01和SNIPR001均使用的是CRISPR/Cas3(单链DNA核酸酶和解旋酶，属于I型CRISPR系统)系统，而非CRISPR/Cas9(双链DNA核酸酶，属于Ⅱ型CRISPR系统)系统，这是因为前者能够在特定位点产生单链缺口，并继续沿DNA链大片段剪切DNA序列，有利于彻底清除目标基因，因此多用于抗菌领域[27]。在SNIPR001的临床前研究中，Gencay等在8种野生型噬菌体(α15、α17、α20、α31、α33、α46、α48和α51)的基因组中引入CRISPR/Cas3系统后，CRISPR RNA(crRNA)能够引导Cas3蛋白结合并降解E. coli基因组中的目标DNA(包括毒力基因和必需基因)，使82株E. coli菌株的细菌计数均降至检测下限(200 CFU/mL)以下；在启动子PbolA的驱动下，这些噬菌体还能够显著降低大肠埃希菌生物膜的代谢活性，表明SNIPR001对于治疗生物膜相关感染具有潜在益处[24]。
表2对比了传统抗菌药物与噬菌体疗法的特点[28]，相较于传统抗菌药物，噬菌体疗法天然具有窄谱抗菌特性并且可自我扩增，而且其杀菌效果已在广泛体内外研究中得到证实。尤其值得注意的是，病原菌对噬菌体抗性的产生可能反而会恢复其对抗菌药物的敏感性或降低毒力，噬菌体可以通过与外排泵或脂多糖(lipopolysaccharide, LPS)、荚膜抗原等毒力因子特异性结合而黏附于病原菌，若产生噬菌体抗性，则可能导致以上物质表达水平下调，前者能够恢复病原菌对抗菌药物的敏感性[29]，而后者能够使病原菌毒力下降(León等对毒力降低的噬菌体耐药菌株进行了总结[30])或更容易被巨噬细胞吞噬[31]。
但噬菌体疗法也存在一些固有的局限性：噬菌体的极端生物特异性要求用药前检测病原菌对噬菌体的敏感性，否则可能导致治疗失败，也因此从诊断到开始治疗需要经过较长时间；噬菌体难以穿过真核细胞膜，故可能无法治疗胞内感染；细菌裂解后，可能会释放出抗原(如内毒素)，可能导致疾病恶化[28]；作为一种生物产品，噬菌体可能具有免疫原性[32]；噬菌体生产过程中容易掺入细菌抗原等。1.2 抗菌抗体
抗体类药物包括单克隆抗体(monoclonal antibody, mAb，以下简称单抗)、双特异性抗体 (bispecific antibody, BsAb，以下简称双抗)和抗体-药物偶联物(antibody-drug conjugates, ADC)3种，目前研发中的窄谱抗菌药物包含以上全部类型，这是因为绝大多数细菌抗原与人类明显不同，所以存在许多单抗或双抗的理想靶标；此外，抗菌药物具有高度特异性且安全性较好，成为ADC的理想载体。
根据ClinicalTrials检索结果，截至2024年10月，共有20款抗体药物处于临床研发阶段(表3)，与2020年(仅6款抗体药物)相比显著增加[6]。大多数产品处于I期临床试验(9/20，45%)，且绝大多数产品为单抗(18/20，90%)，其余为1款双抗MEDI-3902和1款ADC药物DSTA4637S；靶向的细菌主要为金黄色葡萄球菌(6/20，30%)，其次是肉毒杆菌(3/20，15%)和铜绿假单胞菌(3/20，15%)。
抗菌抗体主要通过以下机制发挥功能：①阻断细菌毒素分泌[33]，如单抗KB001，靶向铜绿假单胞菌Ⅲ型分泌系统(type three secretion system, T3SS) 尖端蛋白PcrV，阻断毒素分泌，然而，KB001在II期临床试验中未能达到疗效终点，另一药物为双抗MEDI-3920，其靶点之一即为PcrV，目前正在进行II期临床试验；②阻断细菌毒素与宿主受体结合，如2016年获批的单抗bezlotoxumab，可通过与艰难梭菌毒素B(TcdB)的CROPS区域结合，阻断TcdB与宿主受体结合[34]，从而预防艰难梭菌感染的复发；③激活补体级联反应，从而导致溶菌作用，抗菌抗体通过Fab端识别并结合细菌抗原(如鞭毛、荚膜多糖、脂多糖等)，Fc端则与补体C1q结合，通过经典途径激活补体，最终形成攻膜复合物(membrane attack complex, MAC)，锚定在细菌细胞膜并破坏局部磷脂双层，形成跨膜通道，导致渗透压改变，最终发挥溶菌作用[35]；④通过抗体介导的吞噬调理作用，促进细菌吞噬和炎症因子分泌。抗菌抗体的Fc端与中性粒细胞或巨噬细胞表面的Fc受体(Fc receptors, FcRs)结合，从而导致抗体依赖性的细菌吞噬作用，并促进TNF-α和IL-1β等炎症因子的分泌[36]。
目前约60%的抗体药物针对的靶点为细菌毒素，通过阻断细菌毒素与宿主受体的结合，从而发挥抗菌作用。对于此类药物，在选择靶标时需要特别考虑该靶标在细菌进化中是否保守。拟治疗金黄色葡萄球菌感染的MEDI-4893所针对的靶点为α毒素(AT，由hla基因编码)，它是一种溶细胞成孔毒素，是脓毒症、皮肤和软组织感染以及肺炎动物模型中的关键致病毒力因子，且在全球金黄色葡萄球菌，包括甲氧西林敏感的金黄色葡萄球菌(MSSA)和甲氧西林耐药的金黄色葡萄球菌(MRSA)等呼吸道分离株中高度保守[37-38]。
与传统抗菌药物相比，抗菌抗体具有独特优势。①由于抗体药物与靶点存在特异性结合，所以天然成为一种窄谱抗菌药物，相较于广谱抗菌药物，有助于降低选择性压力、延缓AMR产生；②抗体与传统抗菌药物的作用机制不同[39]，因而不易产生交叉耐药，从而可为难治细菌感染提供新的治疗选择；③抗体药物是免疫系统的产物，能够与其他免疫活性分子(如补体和细胞因子等)相互协调介导免疫反应(如补体依赖的细胞毒作用和抗体依赖的细胞毒作用)，从而增强抗菌活性[40]。
然而，该类药物仍有一定缺陷。①对病原体快速诊断方法提出更高要求，这是所有窄谱抗菌药物的共性，如果快速诊断方法无法在临床实践中广泛应用，那么窄谱抗菌药物的精准治疗无疑是天方夜谭；②抗体类药物大多需要注射给药，口服生物利用度较低，给药途径不便可能会影响患者依从性；③与其他治疗性蛋白产品类似，抗菌抗体也可能诱导人体产生抗药抗体(anti-drug antibody, ADA)， ADA可能会影响药物的药动学(pharmacokinetics, PK) 特征，还可能导致不良事件，部分具有中和作用的ADA还可能会降低疗效[41]；④相较于传统抗菌药物，抗体类药物的储存和运输条件更为严苛，而且还要持续监测生物或化学污染，从而进一步增加了其临床应用成本[32]。2 临床研发面临的挑战
相较于广谱抗菌药物，窄谱抗菌药物的临床开发可能会面临一些额外的挑战。①具有特定耐药表型的患者数量较少，入组速度受限；②由于临床上快速诊断技术较为匮乏[42]，可能在初期需要进行经验性抗菌治疗，在临床试验方案设计时可以考虑将窄谱抗菌药物作为联合用药或降阶梯疗法用药[6]，但这种做法可能会干扰研究药物在非劣效试验中的有效性评价；③对于潜在的伴随多种细菌感染的患者，可能需要在试验期间持续使用其他广谱抗菌药物，如果广谱抗菌药物与研究药物的抗菌谱有所重合，则会在一定程度上混淆研究药物的有效性评价结果[43]。
面对以上挑战和困难，监管机构可能也会适当放宽要求，依据单个临床试验的说服力、疾病严重程度和紧急程度，FDA可以考虑仅靠1项充分、对照组设置良好的确证性临床试验证据批准药物上市[44]，如注射用舒巴坦钠/度洛巴坦钠(XACDURO®)，其适应症为鲍曼-醋酸钙不动杆菌复合体(ABC)敏感分离株所致医院获得性肺炎(HAP)、呼吸机相关性肺炎(VAP)，仅依靠1项关键Ⅲ期临床试验(n=209，亚胺培南/西司他丁作为背景治疗，黏菌素作为对照组)成功上市[45]。2.1 噬菌体疗法
对于噬菌体疗法这一非传统产品的临床开发还存在一些独特的难题。首先是监管障碍，目前中国仍缺乏相应监管法规，国际上噬菌体相关产品的监管文件也尚在酝酿阶段。FDA在2020年制定了eIND(Emergency Investigational New Drug, 紧急使用研究药物)程序[46]，目前的大多数经验都是在该监管框架下获得的。欧盟尚未批准任何用于人类治疗的噬菌体产品，但从2015年开始，EMA就在积极推动噬菌体产品的结构性和规范性监管法规制定[47]。
第二个重要挑战为PK/PD研究困难。首先是噬菌体作为一种生物产品，其PK特征更为复杂，传统药物研发所积累的经验不再适用。噬菌体疗效很大程度上取决于给药途径，不同给药途径下生物利用度存在明显差异[48]；噬菌体的体内过程(吸收、分布、代谢和排泄，ADME)受噬菌体一般物理性质、细胞类型、微生物组和免疫反应等多种因素的影响(图2)；PK研究困难的最主要原因在于噬菌体自我扩增的独特性，这是以往药物研发中未曾遇到的挑战。
噬菌体可以通过不同途径给药，如口服、吸入和静脉注射。静脉注射可实现噬菌体的完全吸收，而口服和吸入给药后噬菌体的吸收受噬菌体大小、形态及给药部位细胞类型的影响。噬菌体在组织器官的分布取决于噬菌体大小、形态、细胞类型以及微生物组。噬菌体代谢受pH、微生物组和免疫反应的影响。噬菌体的肾脏排泄速率与噬菌体大小呈负相关。
由于噬菌体具有自我扩增(呈非线性且存在密度依赖性)特性，故其动力学特征远远不同于传统抗菌药物，理解噬菌体的动力学特征应从生态相互作用(ecological interaction)的角度出发，而不是采用传统化学反应动力学的视角[49]。
噬菌体杀灭病原菌存在两种途径：第一种为“主动治疗”，即噬菌体经广泛扩增后释放至外界环境，对病原菌造成二次感染来杀灭细菌；第二种为“被动治疗”，即噬菌体初始给药剂量足够大，使其在初次感染时就能杀灭绝大多数病原菌[50]。
“主动治疗”更能体现噬菌体作为自我扩增药物的优势，而要实现“主动治疗”，前提条件为噬菌体成功增殖，这一过程可用基本再生数(R0)[51]来表征，可采用基本生活史参数(即细菌平均复制速率、正常细菌死亡速率和受噬菌体感染细菌的裂解速率等)预测R0，只有R0＞1时，噬菌体才能实现扩增。更进一步理解，R0取决于细菌密度，只有当细菌密度超过增殖阈值(Xp，R0=1时的细菌密度)时，噬菌体才能增殖；将细菌密度达到增殖阈值的时间定义为噬菌体的增殖开始时间(Tp)，只有Tp早于宿主发生有害反应(即病原菌造成的免疫或毒性反应)的时间，才能成功实现“主动治疗”；而在到达Tp之前，必须保证体内尚存噬菌体，若接种时间太早，噬菌体可能被机体清除，从而导致治疗失败，故接种时间必须晚于失败阈值时间(Tf)；与抗菌药物相似的是，噬菌体同样存在淹没阈值，即细菌载量开始下降所需的噬菌体密度，对于“主动治疗”，若增殖后噬菌体的密度始终无法超过淹没阈值，将导致治疗失败，对于“被动治疗”，只有初始给药的噬菌体密度超过淹没阈值，治疗才有可能成功。对于动力学的深入理解会为临床实践带来更加科学的指导：①虽然对于大多数疾病的大多数治疗，一般认为越早越好，而对于噬菌体疗法，过早接种对疾病治疗毫无益处；②噬菌体疗法与抗菌药物联合使用时，必须保证抗菌药物不会干扰噬菌体增殖，否则抗菌药物作用下细菌载量的减少，将导致噬菌体缺乏足够的宿主来实现广泛增殖，从而推迟Tf和Tp，可能导致噬菌体疗法失败、协同作用消失；③无论是“主动治疗”还是“被动治疗”，均需保证噬菌体密度在某一时刻能够超过淹没阈值，否则将导致治疗失败。
其次，对噬菌体PD参数的选择缺乏标准化[52]，噬菌体敏感性检测方法有待进一步研究。通常采用双层或单层琼脂平板法以及浮游生物杀伤试验来评价噬菌体的抗菌活性[53]，目前正在积极探索建立统一方法[54]。
综上所述，目前关于噬菌体疗法的PK/PD研究仍较为有限，Nang等[53]总结了目前已发表的有关PK/PD研究的文献，如Cairns等进行了空肠弯曲菌GIIC8与噬菌体CP8的体外PK/PD研究，并采用数学模型进行了拟合，强调了增殖阈值与淹没阈值在治疗成败中的重要作用[55]，但如何指导临床研究进行剂量设计与给药时间设计仍需进一步探索，成为阻碍噬菌体疗法临床转化的主要障碍(图3)。
2.2 抗体药物
虽然抗体药物在肿瘤和自身免疫性疾病领域表现优异，但在抗感染领域，抗体药物从临床前向临床的转化却面临极大挑战，目前仅3种抗菌抗体被FDA批准，raxibacumab和obiltoxaximab用于治疗炭疽杆菌感染，bezlotoxumab用于治疗艰难梭菌感染[56]，部分抗体药物的临床试验因未达到预期疗效被迫终止。单克隆抗体MEDI-4893的I期临床试验和II期临床试验结果均已发表，I期临床试验结果表明MEDI4893给药后血清AT中和活性大幅增加，并且与药物暴露高度相关(R2=0.91)[57]；然而，Ⅱ期临床试验结果表明MEDI-4893与安慰剂相比30 d金黄色葡萄球菌肺炎发生率无显著差异[58]。双特异性抗体MEDI3902同样未能降低铜绿假单胞菌所致呼吸机相关性肺炎(VAP)的发生率[59]。抗体-抗菌药物偶联物(antibody-antibiotic conjugate, AAC)DSTA4637S的体外研究表明DSTA4637S能够根除人巨噬细胞、内皮细胞以及上皮细胞中的MRSA感染，并能够有效阻止细菌的细胞间转移；在小鼠菌血症模型中，在清除胞内细菌、减少播散性感染方面，DSTA4637S相较于万古霉素的优异疗效也得到了验证，相关工作已发表于Nature[60]；然而，在Ib期的探索性研究中，DSTA4637S治疗组未观察到细菌载量和炎症生物标志物改善趋势[61]。
这些临床研究失败的原因仍在探索，可能为后续药物研发与临床试验设计提供前车之鉴。Centoxin是首个针对革兰阴性菌所致脓毒血症开发的抗体，然而由于抗体缺乏特异性、试验中未严格执行受试者入组标准等等原因，试验结果被FDA质疑，最终流产[62]；某些抗体药物发挥作用可能需依赖于免疫系统，如Pagibaximab可能是因为在免疫功能发育不成熟的新生儿中开展试验最终导致未获得预期疗效[63]；细菌在动物和人体中的免疫逃逸机制可能存在种属差异，尽管动物研究中取得了良好疗效，但在人体试验中有效性仍有可能无法证实[64]。3 未来展望
临床偏好和商业利益所驱动的广谱抗菌药物滥用使AMR愈演愈烈，近年来，新型窄谱抗菌药物的研发逐渐吸引了人们的兴趣，尤其是对于噬菌体疗法和抗菌抗体等非传统产品，临床研发管线呈明显增加。然而，窄谱抗菌药物只有在预期靶点存在、可识别且为主要致病因素时才有效，未能准确理解临床前研究结果和药理规律使这些非传统产品的早期临床试验遭遇了一些失败；而且，相较于广谱抗菌药物，窄谱抗菌药物的临床试验可能将面临特定耐药表型患者入组缓慢、与广谱抗菌药物联用混淆有效性和安全性评价结果等新的挑战。虽然遇到了一些挫折，科学家仍在积极探索新的治疗手段，包括基于CRISPR-Cas3的工程化噬菌体[65]、开发无细胞方法扩增噬菌体[66]、使用脂质体包裹的噬菌体延长有效时间[67]以及噬菌体/抗体与传统抗菌药物联用[68-69]等。
新型窄谱抗菌药物的研发有助于延缓耐药性产生、避免破坏有益菌群以及为死亡率高的严重感染提供有效治疗手段，具有巨大临床价值，伴随着快速诊断技术(如PCR、MALDI-TOF质谱和基因组测序[70])的应用以及严格的抗菌药物管理，有望减缓AMR所带来的全球健康威胁。
利益冲突 所有作者均声明不存在利益冲突
参考文献（略）
来源：齐春业, 冶会静, 武晓捷, 等. 噬菌体与抗体类非传统窄谱抗菌药物临床研发进展与挑战[J]. 中国抗生素杂志, 2025, 50(10): 1123-1134.
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微生物疗法临床研究
100 项与 Exebacase 相关的药物交易
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 右侧感染性心内膜炎 | 临床3期 | 美国 | 2019-12-20 | |
| 金黄色葡萄球菌菌血症 | 临床3期 | 美国 | 2019-12-20 | |
| 金黄色葡萄球菌感染 | 临床3期 | 美国 | 2019-12-20 | |
| 葡萄球菌感染 | 临床3期 | - | - | |
| 葡萄球菌感染 | 临床3期 | - | - | |
| 假体关节感染 | 临床2期 | 法国 | 2023-04-03 | |
| 血源性感染 | 临床2期 | 意大利 | 2017-11-03 | |
| 心内膜炎 | 临床2期 | 比利时 | 2017-05-23 | |
| 心内膜炎 | 临床2期 | 保加利亚 | 2017-05-23 | |
| 心内膜炎 | 临床2期 | 智利 | 2017-05-23 |
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临床结果
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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 |
|---|
临床3期 | 97 | Exebacase + antibiotics | 鹹蓋觸簾構願選範膚艱(蓋齋築築繭窪壓艱夢範) = 繭齋範糧構鬱醖遞膚獵 蓋憲壓積窪鹹獵簾願觸 (窪齋鏇遞壓窪簾廠夢齋 ) | 不佳 | 2024-01-31 | ||
Antibiotics alone | 鹹蓋觸簾構願選範膚艱(蓋齋築築繭窪壓艱夢範) = 鑰積襯鏇簾齋壓獵築廠 蓋憲壓積窪鹹獵簾願觸 (窪齋鏇遞壓窪簾廠夢齋 ) | ||||||
临床3期 | 259 | (Exebacase + SoCA) | 膚憲選遞顧窪築願憲餘 = 鏇繭簾夢獵襯淵構遞鬱 窪廠鬱廠蓋艱醖構繭遞 (醖顧築膚鹹夢鏇衊積築, 願觸醖願網觸構廠鬱淵 ~ 鹹觸網醖鏇顧繭鏇衊顧) 更多 | - | 2023-10-18 | ||
placebo (SoCA Alone) | 膚憲選遞顧窪築願憲餘 = 築廠範淵積簾繭獵膚製 窪廠鬱廠蓋艱醖構繭遞 (醖顧築膚鹹夢鏇衊積築, 選壓衊鏇獵鹹製餘衊顧 ~ 鹹蓋築顧淵選襯夢壓衊) 更多 | ||||||
N/A | 8 | (patients suffering their first episode of CoNS knee PJI) | 膚遞餘遞築衊鑰鑰淵範(淵糧齋糧窪夢鹽艱襯獵) = 艱築簾蓋醖願衊夢壓齋 齋網鹹艱淵夢襯鏇簾艱 (衊築鹽鏇鏇願繭鹽繭鬱 ) 更多 | 积极 | 2022-09-12 | ||
(patients suffering from a complex episode of multi-drug resistant CoNS knee PJI) | 膚遞餘遞築衊鑰鑰淵範(淵糧齋糧窪夢鹽艱襯獵) = 衊顧糧鬱獵鑰網夢積鑰 齋網鹹艱淵夢襯鏇簾艱 (衊築鹽鏇鏇願繭鹽繭鬱 ) 更多 | ||||||
临床2期 | 121 | (CF-301) | 顧築齋鹽積夢繭積淵網 = 願簾壓觸醖鑰鹹鹹鏇鹹 築簾選網製窪餘積憲獵 (鬱淵鑰獵艱糧築窪觸鬱, 憲範窪簾淵遞壓鹽築鬱 ~ 鬱製獵築網窪鹹網願選) 更多 | - | 2021-10-08 | ||
Placebo (Placebo) | 顧築齋鹽積夢繭積淵網 = 鏇壓顧鏇膚選夢鹽範壓 築簾選網製窪餘積憲獵 (鬱淵鑰獵艱糧築窪觸鬱, 醖鏇艱繭網鹹範淵淵獵 ~ 繭衊築顧醖觸糧膚餘鑰) 更多 | ||||||
临床3期 | 259 | 餘餘繭選壓繭齋衊憲壓(遞積艱鹹製獵鹹窪構獵) = 壓齋憲積壓遞鬱蓋淵膚 選夢選夢窪衊鏇艱淵憲 (蓋餘範糧鬱簾壓齋網醖 ) | - | 2021-04-28 | |||
临床2期 | 121 | Exebacase + antibiotics | 築簾醖簾鹽齋蓋鏇觸廠(構鹽艱鏇襯鏇淵醖顧獵) = 願鹽鹹構範齋鑰製選蓋 鑰憲顧憲夢顧襯鏇壓鏇 (壓蓋衊廠鑰遞構醖淵願 ) 更多 | 积极 | 2020-07-01 | ||
Antibiotics alone | 築簾醖簾鹽齋蓋鏇觸廠(構鹽艱鏇襯鏇淵醖顧獵) = 鹽築網製襯簾廠簾網膚 鑰憲顧憲夢顧襯鏇壓鏇 (壓蓋衊廠鑰遞構醖淵願 ) 更多 |
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