Paromomycin or Metronidazole for Symptomatic Dientamoeba Fragilis in Adults (COMFORTER Trial) - Protocol for a Superiority Double Blind, Randomized Controlled Trial

Dientameba Fragilis (D.fragilis) is a protozoan found in the digestive tract - in the human colon. there are disagreements regarding the preferred treatment for these cases, with several regimens tested in mostly small observational studies. Several drugs are currently recommended for D.fragilis, with metronidazole most commonly used. However, metronidazole therapy for treating dientamoebiasis in children was not associated with better clinical outcomes in a randomized, double-blinded and placebo-controlled clinical trial.
Hence, we aim to perform a double blind, randomized controlled trial, evaluating the clinical and microbiological efficacy of paromomycin versus metronidazole for the treatment of symptomatic adults with PCR positive dientamoeba fragilis.
The primary outcomes would be clinical improvement or resolution. Secondary outcomes include clinical improvement evaluated by a visual analogue scale; microbiological eradication, quality of life, and adverse events related to therapy.
We plan to include 60 patients (30 per arm)

开始日期2024-01-22

申办/合作机构

Sheba Medical Center

RBR-4ypn69

/ Not yet recruiting临床3期IIT

Open, randomized clinical trial of efficacy and safety of sequential use ofsingle dose of intralesional meglumine antimoniate and topical paromomycin gelcompared to three intralesional applications of meglumine antimoniate in thetreatment of cutaneous leishmaniasis

开始日期2021-02-01

申办/合作机构

Fundação Oswaldo Cruz

NCT03829917

/ Completed临床2/3期IIT

Oral Miltefosine Plus Topical Paromomycin In American Cutaneous Leishmaniasis

Cure rate for L braziliensis bolivian CL has been 70%-80% for standard systemic and local monotherapies. It would benefit patients if cure rates could be consistently >90%, so testing a combination of two treatments is proposed. The most attractive systemic therapy is the only oral agent, miltefosine during 28 days, and the most attractive local therapy is application of Paromomycin cream for 28 days.

开始日期2019-02-01

申办/合作机构

Alfred Foundation

100 项与硫酸巴龙霉素相关的临床结果

登录后查看更多信息

100 项与硫酸巴龙霉素相关的转化医学

登录后查看更多信息

100 项与硫酸巴龙霉素相关的专利（医药）

登录后查看更多信息

2,403

项与硫酸巴龙霉素相关的文献（医药）

2025-12-01·VETERINARY DERMATOLOGY

World Association for Veterinary Dermatology Consensus Statement for Diagnosis, and Evidence‐Based Clinical Practice Guidelines for Treatment and Prevention of Canine Leishmaniosis

Review

作者: Silvia Colombo ; Chiara Noli ; Gad Baneth ; Domenico Otranto ; Guadalupe Miró ; Alessandra Fondati ; Lluís Ferrer ; Filipe Dantas-Torres ; Laura Ordeix ; Manolis N. Saridomichelakis

ABSTRACT:

Background:

Canine leishmaniosis (CanL) due to Leishmania infantum remains common, and veterinarians do not always follow scientifically sound approaches for diagnosis, treatment and prevention.

Objectives:

To provide consensus guidelines for diagnosis and evidence‐based guidelines for treatment and prevention of CanL.

Methods and Material:

Clinical consensus guidelines for the diagnosis were structured based on literature and authors' experience. Three electronic databases were searched for randomised controlled trials, systematic reviews and meta‐analyses on treatment and prevention.

Results, Conclusions and Clinical Importance:

Diagnosis should be based on compatible clinical signs and/or clinicopathologic abnormalities, exclusion of differentials, demonstration of infection and increased concentration of anti‐ Leishmania IgG (quantitative serology). Euthanasia for public health purposes is not recommended and drugs with anti‐ Leishmania activity should be avoided in subclinically infected dogs. Recommended treatments include meglumine antimoniate‐allopurinol (first‐line treatment), miltefosine‐allopurinol (first‐line treatment) and aminosidine‐allopurinol (second‐line treatment); marbofloxacin may be considered in dogs with advanced chronic kidney disease. In endemic areas, recommended measures for prevention include deltamethrin 4% collar, flumethrin 4.5%‐imidacloprid 10% collar or permethrin 50%‐imidacloprid 10% spot‐on, not using infected blood products for transfusion, not breeding seropositive bitches or dogs with CanL, administration of domperidone (seronegative dogs) and dietary nucleotides‐active hexose correlated compound (subclinically infected, seropositive dogs). Vaccination with Li ESP with MDP may be considered, whereas protein Q vaccine is recommended in areas with very high rates of seroconversion. In non‐endemic areas, recommended measures include not using infected blood products for transfusion and removal of infected female dogs from reproduction.

2025-12-01·ANTONIE VAN LEEUWENHOEK INTERNATIONAL JOURNAL OF GENERAL AND MOLECULAR MICROBIOLOGY

Insights into genetic heterogeneity and drug resistance in Leishmania donovani of the Indian sub-continent from genomic data

Article

作者: Kumari, Indu ; Verma, Aroop ; Jha, Anupam Nath

Leishmaniasis is one of the neglected tropical diseases that is endemic to over 90 countries, and its cases are being reported from non-endemic countries as well, like Austria. The cases of visceral leishmaniasis, caused by Leishmania donovani are concentrated on the Indian Subcontinent. There are several studies on the genetic heterogeneity, aneuploidy, and drug resistance emergence from Indian subcontinent as well as globally. However, no research has yet inspected the genomic data from the Indian subcontinent to conduct a comprehensive investigation at the nucleotide level of the genome. We have considered whole-genome sequence data from the publicly available database, i.e., European Nucleotide Archive. Genetic analysis has shown that there is tetraploidy in chromosome 31, trisomy in chromosomes 2 and 8, and trisomy was observed a in chromosomes 6 and 15 among some samples. This aneuploidy pattern is evolving over time as observed in the present study. The paromomycin drug has induced trisomy in chromosome 2. The pattern of aneuploidy variations in samples from the Indian subcontinent differs markedly from that in other continent's samples. Further, ATP-binding cassette family, Amastin-like surface proteins, A2 genes, amino acid permeases, heat shock 70-related protein 1, mitochondrial precursor, putative, partial and sodium stibogluconate resistance protein, putative proteins were those that exhibited the maximum number of mutations amid all the analyzed samples. The proteins showing higher number of mutations belong to membrane proteins that are involved in drug resistance mechanism. Most of these proteins are involved in the virulence and drug resistant mechanism (like transporter proteins). The present study provides the possible candidates which can be targeted to disarm the virulence of the protozoan and drug candidates for therapeutic interventions.

2025-10-24·JOURNAL OF NATURAL PRODUCTS

Hygromycin B Is a Highly Versatile Inducer of Secondary Metabolite Production Applicable Across Diverse Fungal Taxa

Article

作者: Hayashi, Yuki ; Kato, Sho ; Iwatsuki, Masato ; Nonaka, Kenichi ; Watabe, Mika ; Ibuki, Ryoya ; Kojima, Hiroki ; Inahashi, Yuki ; Kikuchi, Yuta ; Watanabe, Yoshihiro ; Tsutsumi, Hayama

Hygromycin B, a well-known antibiotic agent, was recently reported as an inducer of secondary metabolites for a fungal strain of Fusarium sp. In this study, we verified the versatility and usefulness of hygromycin B as an inducer of fungal secondary metabolite production. We demonstrate that hygromycin B induces the production of various fungal secondary metabolites, including polyketides, peptides, and terpenes, in 71% of 28 fungal strains belonging to the Ascomycota phylum, specifically within the Eurotiomycetes, Sordariomycetes, and Dothideomycetes classes. We also demonstrate the discovery of novel compounds, named hannocateol (1) and shirazines A (2) and B (3), from the hygromycin B-supplemented cultured materials. The production of the novel compounds increased with hygromycin B-supplementation up to 100 μg/g (maximum >100-fold) but not by HDAC inhibitors, protein synthesis inhibitors against prokaryotes, and antifungal agents. Notably, protein synthesis inhibitors against eukaryotes similar to hygromycin B, such as 5-fluorouracil and paromomycin, could induce the production of 1 and 2, suggesting that its mechanism would be associated with protein synthesis inhibition. We proved that hygromycin B is a highly versatile inducer of secondary metabolite production applicable across diverse fungal taxa, making it a simple and powerful tool for uncovering cryptic biosynthetic pathways and discovering novel bioactive compounds.

项与硫酸巴龙霉素相关的新闻（医药）

2025-12-03

·北京医学感染与传染研究

抗菌化疗杂志 80卷 7-12期、增刊2、4期（2025年12月3日更新）

Journal of Antimicrobial Chemotherapy Volume 80, Issue 7抗菌化疗杂志 80卷 7期 https://academic.oup.com/jac/issue REVIEWS（综述） 1 The role of antimicrobial prophylaxis in brachytherapy for prostate, breast and gynaecological cancer: a narrative review 抗生素预防用药在前列腺、乳腺及妇科癌症近距离治疗中的作用：叙述性综述 Konstantinos Alexakis and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1753–1771, 2 To be or not to be: the non-antimicrobial properties of common antimicrobials 生存还是毁灭：常见抗菌药物的非抗菌特性 Shivakumar Narayanan and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1772–1783, SYSTEMATIC REVIEWS（系统综述） 3 Antibiotic-induced Bartter-like syndrome: a systematic review 抗生素诱发的巴特综合征样表现：系统综述 Megha Priyadarshi and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1784–1791, 4 Liposomal amphotericin B prophylaxis in paediatrics: a systematic review 两性霉素B脂质体预防性用药在儿科中的应用：系统综述 Emma V Thorley and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1792–1802, ORIGINAL RESEARCH（论著） 5 Antibiotic use attributable to RSV infections during infancy—an international prospective birth cohort study 婴儿期呼吸道合胞病毒感染所致抗生素使用情况——一项国际前瞻性出生队列研究 Sarah F Hak and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1803–1812, 6 Plasmodium falciparum isolates: ex vivo drug response 恶性疟原虫分离株：体外药物反应 Edem Adika and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1813–1822, 7 Impact of hypoalbuminemia on patients receiving ertapenem combination therapy for methicillin-susceptible Staphylococcus aureus bacteraemia 低白蛋白血症对接受厄他培南联合疗法治疗甲氧西林敏感金黄色葡萄球菌菌血症患者的影响 Sunish Shah and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1823–1827, 8 Exploring community pharmacy professionals and general practitioners’ views on primary care communication and pathways to access antibiotics in England 探究英国社区药房专业人员和全科医生对初级保健沟通及获取抗生素途径的看法 Ming Xuan Lee and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1828–1836, 9 Decline of antimicrobial resistance in Pseudomonas aeruginosa bacteraemia following the COVID-19 pandemic: a longitudinal observational study 新冠疫情后铜绿假单胞菌菌血症抗菌药物耐药性的下降：一项纵向观察研究 Yulia Butscheid and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1837–1848, 10 Selected comorbidities and the probability of ART switch in PWH with undetectable HIV-RNA: a retrospective analysis in Italy 意大利HIV感染者（HIV-RNA不可检测）特定合并症与抗逆转录病毒药物转换概率：一项回顾性分析 Alessandro Cozzi-Lepri and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1849–1859, 11 Model-based translation of the PKPD-relationship for linezolid and vancomycin on methicillin-resistant Staphylococcus aureus: from in vitro time–kill experiments to a mouse pneumonia model 基于模型转化利奈唑胺和万古霉素对甲氧西林耐药金黄色葡萄球菌的药代动力学-药效学关系：从体外时间杀菌实验到小鼠肺炎模型 Diego Vera-Yunca and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1860–1868, 12 Inner-mitochondrial membrane protein PfMPV17 is linked to P. falciparum in vitro resistance to the indoloquinolizidine alkaloid alstonine 线粒体内膜蛋白PfMPV17与恶性疟原虫对吲哚醌啉生物碱阿尔斯通宁的体外耐药性相关 J R Macdonald and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1869–1877, 13 Efficacy and tolerability of the combination of minocycline and metronidazole for macrolide-resistant Mycoplasma genitalium 米诺环素与甲硝唑联合治疗大环内酯类耐药生殖支原体感染的疗效和耐受性 Kay Htaik and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1878–1884, 14 Early use of the novel antifungal rezafungin: a case series and literature review 新型抗真菌药物瑞扎芬净的早期使用：病例系列报道及文献综述 H C Davidson and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1885–1892, 15 Optimal dosing of amoxicillin in obese and post-gastric bypass patients using a population pharmacokinetics-pharmacodynamics model approach 基于群体药代动力学-药效学模型方法确定阿莫西林在肥胖和胃旁路术后患者中的最佳剂量 Gisela Myrian de Lima Leite Dalla Rosa and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1893–1901, 16 Decreasing antimicrobial resistance in representative UK livestock species was associated with reduced total sales of antimicrobials in the last decade 过去十年，英国代表性家畜物种抗菌药物耐药性下降与抗菌药物总销量减少相关 Aliya El Nagar and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1902–1906, 17 An improved multiplex RT–quantitative PCR assay can reveal sex-specific activity of transmission-blocking drugs on ex vivo gametocytes from Plasmodium falciparum asymptomatic infections 一种改进的多重逆转录定量聚合酶链反应检测法可揭示性特异性抗疟疾传播阻断药物对恶性疟原虫无症状感染体外配子体活性的影响 Mariagrazia Ciardo and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1907–1914, 18 Population pharmacokinetics and thrombocytopenia risk assessment of linezolid in liver transplant recipients 利奈唑胺在肝移植受者中的群体药代动力学及血小板减少症风险评估 Xiaoping Shi and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1915–1925, 19 Rapid susceptibility testing on urine for antimicrobial stewardship in general practice 全科实践中的尿液快速药敏试验助力抗菌药物管理 Patrick D J Sturm and Tanja Schülin Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1926–1932, 20 Efficacy of linezolid in monotherapy q12h versus q8h versus combined with daptomycin in the treatment of experimental endocarditis caused by methicillin-resistant and glycopeptide-intermediate Staphylococcus aureus strains 利奈唑胺单药治疗每12小时一次与每8小时一次，以及与达托霉素联合治疗甲氧西林耐药和糖肽中介金黄色葡萄球菌菌株所致实验性心内膜炎的疗效 María-Alexandra Cañas and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1933–1941, 21 In vitro activity of NOSO-502, a novel-action antimicrobial, against clinical strains of Enterobacterales including MDR strains 新型作用机制抗菌药物NOSO-502对包括多重耐药菌株在内的肠杆菌科临床菌株的体外活性 Marie L G Attwood and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1942–1946, 22 Antibacterial activity of propylene glycol against Staphylococcus aureus and Staphylococcus epidermidis in neutral and mild acidic conditions 中性及弱酸性条件下，丙二醇对金黄色葡萄球菌和表皮葡萄球菌的抗菌活性 Nadiia Mosiichuk and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1947–1950, 23 Molecular characteristics of chromosome-mediated colistin resistance in foodborne Salmonella isolates in China 中国食源性沙门氏菌分离株染色体介导的多粘菌素耐药性的分子特征 Zeqiang Zhan and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1951–1963, 24 High azole non-wild type rates and nosocomial microsatellite typing aggregation of Wickerhamomyces anomalus in China according to a 12-year multicenter surveillance study 根据一项为期12年的多中心监测研究，中国异常威克汉姆酵母属唑类非野生型率高且医院内微卫星分型聚集 Zhengyu Luo and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1964–1971, 25 Repurposing antimalarials: pyrimethamine exhibits superior in vitro activity to metronidazole against Gardnerella while sparing Lactobacillus 抗疟药物再利用：乙胺嘧啶对加德纳菌的体外活性优于甲硝唑，且对乳酸杆菌无影响 Aliona S Rosca and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1972–1979, 26 Clinical characteristics and risk factors of tigecycline-induced acute pancreatitis in kidney transplant recipients: a retrospective study 肾移植受者替加环素诱发急性胰腺炎的临床特征及危险因素：一项回顾性研究 Lijuan Feng and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1980–1987, 27 Genomic characteristics of the multiresistant Acinetobacter baumannii global clone 1 reference strain A297/RUH875 多重耐药鲍曼不动杆菌全球克隆1型参考菌株A297/RUH875的基因组特征 Jonathan Koong and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1988–1992, 28 Comparison of a modified broth microdilution Sensititre™ SLOMYCOI assay with the CLSI-recommended agar disk elution method for antimicrobial susceptibility testing of Mycobacterium haemophilum 改良肉汤微量稀释Sensititre™ SLOMYCOI检测法与CLSI推荐的琼脂稀释法对嗜血杆菌属抗菌药物敏感性检测的比较 Doris Hillemann and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1993–1996, 29 Reversal of phenotypic resistance in multi-drug resistant carbapenemase-producing K. pneumoniae clinical isolates due to in vitro synergistic interactions between bacteriophages and antibiotics at clinically achievable concentrations 由于细菌噬菌体和抗生素在临床可达到浓度下的体外协同作用，多重耐药碳青霉烯酶产生肺炎克雷伯菌临床分离株的表型耐药性发生逆转 Paschalis Paranos and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 1997–2006, 30 Antibiotic resistance and population structure of Staphylococcus epidermidis from prosthetic joint infections in Sweden and France 瑞典和法国假体关节感染表皮葡萄球菌的抗生素耐药性和群体结构 Sofie M Edslev and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 2007–2015, 31 Lines on the line: evaluating the impact of antibiotic lock therapy versus catheter removal in the management of central vascular catheter infections 抗生素锁疗法与导管拔除术治疗中心血管导管感染的影响评估 Nischal Ranganath and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 2016–2024, 32 Real-time FT-IR typing of Klebsiella pneumoniae: a flexible and rapid approach for outbreak detection and infection control 肺炎克雷伯菌实时傅里叶变换红外分型：一种灵活快速的暴发检测和感染控制方法 Ana Beatriz Gonçalves and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 2025–2031, 33 Antibiotic stress affects the secretion and physicochemical features of extracellular vesicles produced by Helicobacter pylori 抗生素压力影响幽门螺杆菌产生的细胞外囊泡的分泌和物理化学特性 Paweł Krzyżek and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 2032–2043, 34 A novel azithromycin resistance mutation in Mycoplasma genitalium induced in vitro 生殖支原体体外诱导产生的新型阿奇霉素耐药突变 Teck-Phui Chua and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 2044–2050, RESEARCH LETTERS（研究信函） 35 Posaconazole dosing of enteral formulations in infants and young children to achieve therapeutic concentrations 婴儿和幼儿肠内制剂泊沙康唑的给药剂量以达到治疗浓度 Jeffrey Harrington and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 2051–2053, 36 Antimony used as rescue therapy in a kidney transplant recipient unresponsive to liposomal amphotericin B for chronic visceral leishmaniasis 两性霉素B脂质体治疗慢性内脏利什曼病无效的肾移植受者中使用锑剂作为挽救疗法 Natacha Mrozek and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 2053–2056, 37 Is cefazolin an option for treatment of staphylococcal endogenous endophthalmitis? 头孢唑林是否可用于治疗葡萄球菌性内源性眼内炎？ Alexandra Morin and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 2057–2058, LETTER TO THE EDITOR（致编辑的信） 38 Use of teicoplanin monotherapy for the treatment of enterococcal infective endocarditis: a retrospective and comparative study at a referral centre—a counterpoint 单用替考拉宁治疗肠球菌感染性心内膜炎：一家转诊中心的回顾性和比较研究——反驳观点 Miguel Villamarín and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 7, July 2025, Pages 2059–2060, Journal of Antimicrobial Chemotherapy Volume 80, Issue 8 抗菌化疗杂志 80卷 8期 https://academic.oup.com/jac/issue Review(综述) 1 World Health Organisation’s Bacterial Pathogen Priority List (BPPL) 2017 and BPPL 2024 to combat global antimicrobial resistance crisis: ‘challenges and opportunities’ 世界卫生组织2017年和2024年用以应对全球抗菌药物耐药性危机的细菌病原体优先名单（BPPL）：“挑战与机遇” Vazhayil Hari Krishnaprasad and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2061–2069 Original Research(论著) 2 Aztreonam/avibactam activity against Enterobacterales from European medical centres: summary of 5years of surveillance prior to approval for clinical use (2019–2023) 氨曲南/阿维巴坦对欧洲医疗中心肠杆菌科细菌的活性：临床批准前5年（2019-2023年）监测总结 Helio S Sader and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2070–2079 3 High feasibility of salivary therapeutic drug monitoring in linezolid, but lower feasibility in tedizolid: a single-dose study in healthy subjects and a monocentric prospective exploratory study in patients who received linezolid 利奈唑胺唾液治疗药物监测可行性高，但替地唑胺可行性较低：一项健康受试者单剂量研究和一项接受利奈唑胺患者单中心前瞻性探索性研究 Hitoshi Kawasuji and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2080–2091 4 Establishment and validation of downsized hollow-fibre infection model and pharmacokinetics/pharmacodynamics analysis of VAN on Enterococcus faecium 缩小版中空纤维感染模型的建立与验证及万古霉素对粪肠球菌的药代动力学/药效学分析 Yukitaka Hayashi and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2092–2099 5 Four-month clofazimine regimen for susceptible pulmonary TB: a randomized clinical trial 为期4个月的氯法齐明方案治疗敏感型肺结核：一项随机临床试验 Nusrat Shafiq and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2100–2108 6 An ex vivo model to determine transmembrane clearance of antimicrobials during continuous renal replacement therapy 用于确定连续性肾脏替代治疗期间抗菌药物跨膜清除率的体外模型 Cole McGrath and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2109–2116 7 Optimization and improvement of the disc diffusion method for mucoid Pseudomonas aeruginosa 黏液型铜绿假单胞菌纸片扩散法的优化与改进 Aixin Wang and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2117–2125 8 HIV-1 drug resistance among people living with HIV receiving dolutegravir-based anti-retroviral regimens in Uganda: a national laboratory-based survey using remnant viral load samples, 2022 乌干达接受基于多替拉韦抗逆转录病毒方案的HIV感染者中HIV-1耐药性情况：2022年一项基于国家实验室使用剩余病毒载量样本的调查 Christine Watera and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2126–2134 9 Population pharmacokinetics of weight-based compared with fixed dosing of CAP256V2LS, a broadly neutralizing antibody for HIV prevention in women 与固定剂量相比，基于体重给药的CAP256V2LS（一种用于女性HIV预防的广谱中和抗体）群体药代动力学研究 Sharana Mahomed and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2135–2144 10 Gut microbiota and weight gain in people with HIV on integrase inhibitors: a five-year longitudinal study 接受整合酶抑制剂治疗的HIV感染者肠道微生物群与体重增加情况：一项为期五年的纵向研究 Javier García-Abellán and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2145–2157 11 Development of a ribavirin dosing regimen in transplant recipients with chronic hepatitis E virus infection: a population pharmacokinetic and -dynamic model 慢性戊型肝炎病毒感染移植受者利巴韦林给药方案的开发：一项群体药代动力学和药效学模型研究 Midas B Mulder and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2158–2168 12 Effectiveness and predictors of treatment discontinuation of long-acting cabotegravir/rilpivirine in virologically suppressed people with HIV: real-life data from the Icona Cohort 长效卡博特韦/利匹韦林在病毒受抑制的HIV感染者中的治疗中断有效性和预测因素：来自Icona队列的现实数据 Roberta Gagliardini and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2169–2178 13 Five-days-on-two-days-off (FOTO) versus daily bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed people with HIV: a pilot randomized clinical trial 病毒受抑制的HIV感染者中，5天用药2天停药（FOTO）方案与每日比克替拉韦/恩曲他滨/丙酚替诺福韦方案的对比：一项初步随机临床试验 Hsin-Yun Sun and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2179–2186 14 Reliability of disc diffusion testing and molecular epidemiology of penicillin-susceptible Staphylococcus aureus bacteraemia 青霉素敏感金黄色葡萄球菌菌血症的纸片扩散试验可靠性和分子流行病学研究 Pernilla Kihlberg and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2187–2193 15 Outcomes of ceftriaxone 2g versus 1g daily in hospitalized patients with pneumonia: a nationwide retrospective cohort study 住院肺炎患者每日头孢曲松2克与1克疗效对比：一项全国性回顾性队列研究 Jumpei Taniguchi and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2194–2202 16 Oleanolic acid derivative bardoxolone combats multidrug-resistant Staphylococcus aureus by destroying cell membrane and pyruvate metabolism pathway 齐墩果酸衍生物巴多昔隆通过破坏细胞膜和丙酮酸代谢途径对抗多重耐药金黄色葡萄球菌 Yun-Dan Zheng and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2203–2213 17 Evaluation of amoxicillin and benzylpenicillin therapy in early-onset neonatal sepsis: a pharmacometric external validation and simulation study 阿莫西林和苄青霉素治疗早期新生儿败血症的评估：一项药效计量学外部验证和模拟研究 Tom C Zwart and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2214–2225 18 48Week body composition changes in persons with HIV switching to dolutegravir plus lamivudine: a planned subanalysis of the DOLAM randomized clinical trial HIV感染者换用多替拉韦加拉米夫定治疗48周身体成分变化：DOLAM随机临床试验的计划子分析 Elisa de Lazzari and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2226–2233 19 The impact of inter-infection time on antimicrobial resistance profiles in women with multiple urinary tract infections over time 多次尿路感染女性患者感染间隔时间对抗菌药物耐药性特征的影响 Trenton Honda and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2234–2240 20 Development and evaluation of a novel rapid immunochromatographic assay for the detection of DHA-producing Enterobacterales 一种检测产DHA肠杆菌科细菌的新型快速免疫层析法的开发与评估 Christian Moguet and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2241–2246 21 Enterococcus faecium bacteraemia: a multicentre observational study focused on risk factors for clinical and microbiological outcomes 粪肠球菌菌血症：一项关注临床和微生物学结局风险因素的多中心观察性研究 Matteo Rinaldi and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2247–2256 22 Indolocarbazoles as host-directed therapeutics against intracellular infections by methicillin-resistant Staphylococcus aureus 靛红咔唑类化合物作为宿主导向疗法对抗甲氧西林耐药金黄色葡萄球菌细胞内感染 Robin H G A van den Biggelaar and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2257–2268 23 Clinical validation of antimicrobial dosing regimens for continuous renal replacement therapy based on an ex vivo dosing algorithm 基于体外给药算法的连续性肾脏替代治疗抗菌药物给药方案的临床验证 Christina Koenig and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2269–2279 24 Novel integrative and conjugative elements carrying cfr(B) and cfr(C) linezolid resistance genes in Clostridioides difficile isolates from calves, Italy 意大利牛犊艰难梭菌分离株中携带cfr(B)和cfr(C)利奈唑胺耐药基因的新型整合性和接合性元件 Andrea Brenciani and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2280–2284 25 Characterization of Carbapenemase-producing Enterobacterales isolated from patients returning from Sub-Saharan Africa, France, 2015–2022 2015-2022年从撒哈拉以南非洲返回的法国患者中分离出的产碳青霉烯酶肠杆菌科细菌的特征 Corentin Poignon and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2285–2294 26 Penicillin-susceptible ST398 with strong biofilm-forming ability poses a significant threat to osteoarticular infections 具有强生物膜形成能力的青霉素敏感ST398型对骨关节感染构成重大威胁 Ye Jin and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2295–2304 27 Cardiac safety of bedaquiline, delamanid and moxifloxacin co-administered with or without varying doses of sutezolid or delpazolid for the treatment of drug-susceptible TB 贝达喹啉、德拉马尼和莫西沙星与不同剂量苏特唑利或德帕唑利联合用药治疗药物敏感型肺结核的心脏安全性 Simon E Koele and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2305–2313 28 Comparison of ceftolozane/tazobactam and meropenem in treating bloodstream infections caused by extended-spectrum β-lactamase-producing Enterobacterales: a single-centre, retrospective, real-world study 头孢托唑坦/他唑巴坦与美罗培南治疗产超广谱β-内酰胺酶肠杆菌科细菌所致血流感染的对比：一项单中心回顾性现实研究 Dimitrios Basoulis and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2314–2322 Research Letters(研究信件) 29 Dalbavancin as chronic suppressive therapy in a patient undergoing monthly apheresis: a case report with therapeutic drug monitoring 达巴万星作为每月进行血浆置换术患者的长期抑制治疗：一项带治疗药物监测的病例报告 Carlo Pallotto and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2323–2324 30 A novel methicillin-resistant Staphylococcus aureus lineage (ST4174) with an uncharacterized SCCmec variant identified in Korean pigs 韩国猪体内发现的一种带有未表征SCCmec变体的新型甲氧西林耐药金黄色葡萄球菌谱系（ST4174） Hyeonwoo Cho and Kun Taek Park Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2325–2326 31 Time fixes everything, but not always: 10years of persistent PI mutations in the absence of pharmacological pressure—a case report 时间能治愈一切，但并非总是如此：无药物压力下持续10年的蛋白酶抑制剂突变——一例病例报告 Layla Pagnucco and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2327–2330 32 Carbapenem resistance in Escherichia marmotae: characterization of IncL plasmids carrying blaOXA-48 土拨鼠埃希菌的碳青霉烯耐药性：携带blaOXA-48的IncL质粒特征 Astrid Rasmussen and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2330–2331 Letters to the Editor(致编辑的信) 33 Comment on: Clinical outcomes and the impact of treatment modalities in children with carbapenem-resistant Enterobacteriaceae bloodstream infections: a retrospective cohort study from a tertiary university hospital 述评：产碳青霉烯酶肠杆菌科细菌血流感染患儿的临床预后和治疗方式的影响：一项来自三级大学医院的回顾性队列研究 Jianjun Li and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Page 2332 34 Clinical outcomes and the impact of treatment modalities in children with carbapenem-resistant Enterobacteriaceae bloodstream infections: a retrospective cohort study from a Tertiary University Hospital—right to reply—author’s response 产碳青霉烯酶肠杆菌科细菌血流感染患儿的临床预后和治疗方式的影响：一项来自三级大学医院的回顾性队列研究——作者回复 Gulhadiye Avcu Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Pages 2332–2333 Corrections(更正) 35 Correction to: Sofosbuvir as post-exposure prophylaxis for yellow fever–associated viscerotropic disease (YEL-AVD) 更正：索非布韦作为黄热病相关内脏热带病（YEL-AVD）暴露后预防用药 Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Page 2334 36 Correction to: Pandemic human-associated extended-spectrum β-lactamase-producing Escherichia coli lineages of ST38, ST131 and ST141 identified in Viennese dogs 更正：维也纳犬体内发现与人相关的大流行性产超广谱β-内酰胺酶大肠杆菌ST38、ST131和ST141谱系 Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Page 2335 37 Correction to: GP or ChatGPT? Ability of large language models (LLMs) to support general practitioners when prescribing antibiotics 更正：全科医生还是ChatGPT？大型语言模型（LLM）在全科医生开具抗生素处方时的辅助能力 Journal of Antimicrobial Chemotherapy, Volume 80, Issue 8, August 2025, Page 2336 Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_2 抗菌化疗杂志 80卷增刊2期 https://academic.oup.com/jac/issue SUPPLEMENT (补充) CANWARD 2007-23 加拿大抗感染耐药监测项目（CANWARD）2007-2023年数据/报告 Foreword(前言) 1 The CANWARD studies: Canadian Antimicrobial Resistance Alliance (CARA) Canadian Hospital Ward Antibiotic Resistance Surveillance collection 加拿大抗感染耐药监测项目研究：加拿大抗微生物耐药联盟（CARA）加拿大医院病房耐药性监测数据集 James C Hurley and Jean-Yves Madec Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_2, September 2025, Page ii1 Supplement Papers(补充论文) 2 Seventeen years of the CANWARD study (2007–23) 加拿大抗感染耐药监测项目研究17年（2007-2023年） George G Zhanel and Heather J Adam Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_2, September 2025, Pages ii2–ii4 3 Gram-positive pathogens from Canadian hospitals: 17years of results from the CANWARD study (2007–23) 来自加拿大医院的革兰氏阳性病原体：加拿大抗感染耐药监测项目研究的17年结果（2007-2023） George G Zhanel and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_2, September 2025, Pages ii5–ii14 4 Gram-negative pathogens from Canadian hospitals: 17 years of results from the CANWARD study (2007–23) 来自加拿大医院的革兰氏阴性病原体：加拿大抗感染耐药监测项目研究的17年结果（2007-2023） George G Zhanel and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_2, September 2025, Pages ii15–ii26 5 Characterization of methicillin-resistant Staphylococcus aureus in Canadian hospitals: 17 years of the CANWARD study (2007–23) 加拿大医院耐甲氧西林金黄色葡萄球菌的特征：加拿大抗感染耐药监测项目研究的17年（2007-2023） Anissa Brahami and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_2, September 2025, Pages ii27–ii34 6 Comparison of antimicrobial resistance and serotype patterns in Streptococcus pneumoniae from blood cultures and respiratory specimens in Canadian hospitals from the CANWARD study (2007–23) 加拿大抗感染耐药监测项目研究中加拿大医院血液培养和呼吸道标本中肺炎链球菌抗微生物药物耐药性和血清型的比较（2007-23） Heather J Adam and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_2, September 2025, Pages ii35–ii44 7 Increasing rates of ESBL-producing Escherichia coli and Klebsiella pneumoniae in Canadian Hospitals: 17 years of the CANWARD study, 2007–23 加拿大医院中产生ESBL的大肠杆菌和肺炎克雷伯菌的比率增加：加拿大抗感染耐药监测项目研究17年，2007-2023 Philippe Lagacé-Wiens and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_2, September 2025, Pages ii45–ii53 8 Characterization of ertapenem-resistant Enterobacterales in Canadian hospitals: 17 years of the CANWARD study (2007–23) 加拿大医院耐厄他培宁肠杆菌的特征：17年的加拿大抗感染耐药监测项目研究（2007-23） Laura F Mataseje and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_2, September 2025, Pages ii54–ii61 9 Characterization of carbapenem-resistant Pseudomonas aeruginosa in Canadian hospitals: 6years of the CANWARD study (2018–23) 加拿大医院耐碳青霉烯假单胞菌的特征：6年的加拿大抗感染耐药监测项目研究（2018-23） Melissa McCracken and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_2, September 2025, Pages ii62–ii71 10 Distribution and antimicrobial susceptibility profile of pathogens recovered from the bloodstream of Canadian patients: results from the CANWARD study (2007–23) 加拿大患者血液中病原菌的分布和药敏特征：来自加拿大抗感染耐药监测项目研究（2007-23）的结果 Andrew Walkty and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_2, September 2025, Pages ii72–ii82 Journal of Antimicrobial Chemotherapy Volume 80, Issue 9抗菌化疗杂志 80卷 9期 https://academic.oup.com/jac/issue VIEWPOINT（观点） 1 Classifying patients with invasive fungal disease: towards a unified case definition? 侵袭性真菌病患者分类：能否达成统一的病例定义？ Mehmet Ergün and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2337–2343, SYSTEMATIC REVIEW（系统综述） 2 Efficacy and safety of earlier switching to an oral antibiotic therapy for the treatment of Gram-positive bloodstream infections: a systematic review and meta-analysis 早期转换为口服抗生素治疗革兰氏阳性菌血流感染的疗效和安全性：一项系统综述和荟萃分析 ZhaoYi Tan and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2344–2360, ORIGINAL RESEARCH（论著） 3 Determination of epidemiological cut-off values for Narasin, Salinomycin, Lasalocid and Monensin in Enterococcus faecium 屎肠球菌中那拉霉素、盐霉素、拉沙洛西钠和莫能菌素流行病学临界值的测定 Maria Laura Ferrando and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2361–2368, 4 Persistence of CXCR4-tropic virus in people living with four-class drug-resistant HIV and its clinical impact in the modern antiretroviral era 四类耐药HIV感染者体内CXCR4嗜性病毒的持续存在及其在现代抗逆转录病毒治疗时代的临床影响 Rebecka Papaioannu Borjesson and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2369–2374, 5 Hypertension and blood pressure changes with dolutegravir or comparator antiretroviral therapy in randomized trials through 96 weeks 随机试验中96周内使用多替拉韦或对照抗逆转录病毒疗法对高血压和血压变化的影响 Parul Patel and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2375–2383, 6 Comparative analysis of lipid profile changes in treatment-naïve people living with HIV on INSTI-based single-tablet regimens, BIC/FTC/TAF and DTG/3TC: real-world evidence from South Korea 基于整合酶抑制剂的单片复方制剂BIC/FTC/TAF和DTG/3TC在韩国初治HIV感染者中血脂谱变化的比较分析：来自现实世界的证据 So Yun Lim and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2384–2390, 7 A novel multilocus sequence typing scheme for Morganella spp.: population structure and introduction of quantitative metric for standardization of MLST scheme 摩根氏菌属的一种新型多位点序列分型方案：群体结构及引入用于标准化多位点序列分型方案的定量度量标准 Aymeric Jacquemin and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2391–2398, 8 Genomic characterization of multidrug-resistant extended-spectrum β-lactamase-producing Vibrio cholerae O1 strains from 2022 cholera outbreak in Kenya 2022年肯尼亚霍乱疫情中产超广谱β-内酰胺酶的多重耐药霍乱弧菌O1株的基因组特征 Diana Imoli and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2399–2407, 9 Impact of empiric anti-VRE therapy on survival in vancomycin-resistant enterococcal bloodstream infection 经验性抗万古霉素耐药肠球菌治疗对万古霉素耐药肠球菌血流感染患者生存率的影响 Tao-Hung Ou and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2408–2416, 10 Safety of topical tobramycin powder during operative treatment of fractures 骨折手术中使用局部妥布霉素粉末的安全性 Gregory M Schrank and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2417–2420, 11 Trimethoprim/sulfamethoxazole and risk of haemophagocytic lymphohistiocytosis (HLH): a literature review and disproportionality analysis using individual case safety reports from FAERS 复方磺胺甲恶唑与噬血细胞性淋巴组织细胞增多症（HLH）的风险：基于FAERS数据库个案安全报告的文献综述和比例失衡分析 Rinko Lau and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2421–2427, 12 Highly drug-resistant Vibrio cholerae harbouring blaPER-7 isolated from travellers returning to England 从返回英国的旅行者中分离出携带blaPER-7基因的高度耐药霍乱弧菌 Satheesh Nair and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2428–2432, 13 Overcoming antimicrobial resistance in Helicobacter pylori: the roles of collateral sensitivity and biofilm dynamics 克服幽门螺杆菌的抗菌药物耐药性：附带敏感性和生物膜动态的作用 Siddharth Singh and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2433–2441, 14 Clinical and microbiological analysis of bloodstream infections by four cefiderocol-resistant and not previously exposed NDM-producing Klebsiella pneumoniae 四种未接触过但对头孢地尔耐药的产NDM肺炎克雷伯菌所致血流感染的临床和微生物学分析 Maria Mazzitelli and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2442–2446, 15 Synergistic effects of DHA27 combined with gentamicin against methicillin-resistant Staphylococcus aureus in vitro and in vivo DHA27与庆大霉素联合对耐甲氧西林金黄色葡萄球菌的体内外协同作用 Xuemin Chen and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2447–2458, 16 A multicentre study for determination of epidemiological cut-off values for Candida auris with EUCAST broth microdilution reference methodology 采用EUCAST肉汤微量稀释参考方法进行耳念珠菌流行病学临界值的多中心测定研究 Joseph Meletiadis and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2459–2465, 17 Impact of vancomycin resistance on attributable mortality among Enterococcus faecium bloodstream infections: propensity score analysis of a large, multicentre retrospective study 万古霉素耐药对屎肠球菌血流感染归因死亡率的影响：一项大型多中心回顾性研究的倾向评分分析 M Del Monte and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2466–2473, 18 Dynamics of dual CMV and EBV co-reactivation and emergence of resistance in an HSCT recipient 异基因造血干细胞移植受者中CMV和EBV双重再激活的动态变化及耐药性的出现 Martyna Pociupany and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2474–2483, 19 Antimicrobial use for the treatment of bacterial sexually transmitted infections among doxycycline post-exposure prophylaxis (DoxyPEP) users in Milan, Italy 意大利米兰多西环素暴露后预防（DoxyPEP）使用者中用于治疗细菌性性传播感染的抗菌药物使用情况 Angelo Roberto Raccagni and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2484–2486, 20 Comparing the mortality of patients with sepsis using empirical piperacillin/tazobactam and cefepime: analysis of the MIMIC-IV database 使用经验性哌拉西林/他唑巴坦和头孢吡肟的脓毒症患者死亡率比较：基于MIMIC-IV数据库的分析 Yongseop Lee and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2487–2495, 21 Transmitted drug resistance profiles among people living with HIV-1 in Henan province, China, 2024 2024年中国河南省HIV-1感染者传播耐药情况 Jinjin Liu and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2496–2502, 22 Fluctuations in copy number of the class A carbapenemase gene blaFRI appear to confer high-level carbapenem resistance A类碳青霉烯酶基因blaFRI拷贝数的波动似乎赋予了高水平碳青霉烯耐药性 Makiko Noda and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2503–2512, 23 In vitro activity of ceftobiprole plus ampicillin against Enterococcus faecalis causing infective endocarditis: phenotypic and genotypic characterization 头孢比罗联合氨苄西林对引起感染性心内膜炎的粪肠球菌的体外活性：表型和基因型特征 Clara Moretó-Castellsaguéand others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2513–2523, 24 Paradoxical interaction between dalbavancin and β-lactams against endocarditis-associated Enterococcus faecalis clinical isolates 达巴万星与β-内酰胺类药物对心内膜炎相关粪肠球菌临床分离株的矛盾相互作用 David Luque Paz and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2524–2529, 25 Comparative evaluation of broth microdilution and gradient diffusion methods in Burkholderia cepacia complex susceptibility testing: implications of transitioning to ECV-based interpretation 伯克霍尔德菌复合群药敏试验中肉汤微量稀释法和梯度扩散法的比较评估：向基于ECV解释转变的影响 Wenjie Cui and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2530–2540, 26 Strengthening antimicrobial resistance diagnostics in National Reference Laboratories across One Health in South and Southeast Asia: impact of external quality assessment and targeted follow-up 加强南亚和东南亚“同一健康”国家参考实验室的抗菌药物耐药性诊断能力：外部质量评估和针对性随访的影响 Freshwork Ayalew Abegaz and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2541–2549, RESEARCH LETTERS（研究快信） 27 TDM-guided meropenem/vaborbactam-based therapy for successful treatment of intra-abdominal and bloodstream infection caused by KPC-producing ceftazidime/avibactam-resistant Klebsiella pneumoniae in a paediatric liver transplant recipient 治疗药物监测指导下的美罗培南/瓦博巴坦疗法成功治疗儿童肝移植受者中产KPC且对头孢他啶/阿维巴坦耐药的肺炎克雷伯菌引起的腹腔和血流感染 Giovanni Mulé and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2550–2552, 28 Novel tmexC7D2-toprJ5 gene cluster and transposon Tn7759 carrying blaVIM-2 and blaOXA-10 genes in a carbapenem-resistant Pseudomonas putida from urban sewage 城市污水中碳青霉烯耐药恶臭假单胞菌中携带blaVIM-2和blaOXA-10基因的新型tmexC7D2-toprJ5基因簇和转座子Tn7759 Xinyuan Qiu and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2552–2555, 29 Characterization of multiresistance gene optrA in Bacillus subtillis from China 中国枯草芽孢杆菌中多重耐药基因optrA的特征分析 Yongliang Che and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2555–2557, 30 Genomic characterization of a multidrug-resistant Mammaliicoccus sciuri strain isolated from urine of a patient from China 从中国患者尿液中分离出的一株多重耐药马氏鼠球菌的基因组特征 Fuqiang Ye and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2558–2560, LETTERS TO THE EDITOR（致编辑的信） 31 Comment on: Isavuconazole therapeutic drug monitoring and association with adverse events 关于“艾沙康唑治疗药物监测及其与不良反应的关联”的评论 Mi Zhou and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2561–2562, 32 Comment on: Outcomes of ceftriaxone 2 g versus 1 g daily in hospitalised patients with pneumonia: a nationwide retrospective cohort study 关于“住院肺炎患者每日2克与1克头孢曲松疗效比较：一项全国性回顾性队列研究”的评论 Satoru Mitsuboshi Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Page 2563, 33 Outcomes of ceftriaxone 2 g versus 1 g daily in hospitalized patients with pneumonia: a nationwide retrospective cohort study—authors’ response 住院肺炎患者每日2克与1克头孢曲松疗效比较：一项全国性回顾性队列研究——作者回复 Jumpei Taniguchi and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 9, September 2025, Pages 2563–2564, Journal of Antimicrobial Chemotherapy Volume 80, Issue 10抗菌化疗杂志 80卷 10期 https://academic.oup.com/jac/issue REVIEWS（综述） 1 Long-acting cabotegravir and rilpivirine for the treatment of people with HIV: current landscape and challenges ahead 长效卡博特韦和利匹韦林治疗HIV感染者的现状与未来挑战 Luis Buzón-Martín and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2565–2586, 2 Systematic reviews and the Journal of Antimicrobial Chemotherapy; past, present and future. A systematic reappraisal 系统综述与《抗菌化疗杂志》：过去、现在与未来——系统再评估 James C Hurley Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2587–2596, SYSTEMATIC REVIEWS（系统综述） 3 Studying intrapulmonary pharmacokinetics for tuberculosis treatment: a systematic review of methodology 研究肺结核治疗的肺内药代动力学：方法学的系统综述 Isabella van der Feltz and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2597–2608, 4 Global prevalence of nitrofurantoin-resistant uropathogenic Escherichia coli (UPEC) in humans: a systematic review and meta-analysis 全球人类中耐呋喃妥因的尿路致病性大肠埃希菌（UPEC）流行率：系统综述与荟萃分析 Christopher Larkin and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2609–2621, ORIGINAL RESEARCH（研究论著） 5 Is ampicillin plus cephalosporins a therapeutic option for Ampicillin-Susceptible Enterococcus faecium? 氨苄青霉素联合头孢菌素是否为氨苄青霉素敏感的粪肠球菌的治疗选择？ Paula Bierge and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2622–2629, 6 Therapeutic efficacy monitoring of pyronaridine–artesunate (Pyramax®) in treating uncomplicated Plasmodium falciparum malaria in Gia Lai province, Vietnam from 2022 to 2023 2022-2023年越南嘉莱省青蒿琥酯-吡咯尼抗（Pyramax®）用于无并发症恶性疟原虫疟疾的治疗效果监测 Nguyen Van Thanh and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2630–2634, 7 Effectiveness of piperacillin/tazobactam loading dose for extended infusion dosing among patients with Gram-negative bacteraemia 哌拉西林/他唑巴坦负荷剂量用于革兰氏阴性菌血症患者延长输注给药的有效性 Savan Patel and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2635–2643, 8 Intrapulmonary concentrations of ceftobiprole high doses administered by continuous infusion in critically ill patients with community-acquired pneumonia 连续输注大剂量头孢比罗在社区获得性肺炎危重患者中的肺内浓度 Claire Roger and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2644–2653, 9 Cefixime versus benzathine penicillin G for the treatment of early syphilis—a randomized, controlled open label trial 头孢克肟与苄星青霉素G治疗早期梅毒的随机对照开放标签试验 Tamara Klementová and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2654–2658, 10 Trends in antifungal use among hospitalized patients in the USA, 2018–23 2018-2023年美国住院患者抗真菌药物使用趋势 Dallas J Smith and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2659–2664, 11 Clinical impact of the BCID2 and rapid AST VITEK® REVEALTM on antibiotic optimisation in critically ill patients with Gram-negative bloodstream infections: a quasi-experimental pre/post interventional study BCID2和快速AST VITEK® REVEALTM对革兰氏阴性菌血流感染危重患者抗生素优化的临床影响：一项准实验性前后干预研究 Louis Oudiane and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2665–2675, 12 In vitro activity of thiamphenicol against drug-susceptible and drug-resistant strains of Mycoplasma genitalium 甲砜霉素对药物敏感和耐药生殖支原体菌株的体外活性 Sofie Skovmand and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2676–2681, 13 A priori optimization of levofloxacin dose regimen based on a population pharmacokinetics model 基于群体药代动力学模型的左氧氟沙星剂量方案先验优化 Emmanuel Enard and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2682–2692, 14 Model-informed individualized administration of ceftazidime–avibactam in critically ill patients: population pharmacokinetics studies and a parametric time-to-event analysis 危重患者头孢他啶-阿维巴坦的模型知情个体化给药：群体药代动力学研究和参数时间事件分析 Tingting Wu and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2693–2704, 15 Development of blood culture time-to-positivity as a pharmacodynamic indicator for monitoring antibiotic therapy against MDR Gram-negative bacteria 开发血培养阳性时间作为监测针对多重耐药革兰氏阴性菌抗生素治疗的药效动力学指标 Irene Zaghi and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2705–2713, 16 In vivo activity of ceftibuten-ledaborbactam oral combination against serine-β-lactamase-producing Enterobacterales: an assessment in the pyelonephritis and cystitis murine model 头孢布坦-莱达博巴坦口服联合用药对产丝氨酸-β-内酰胺酶肠杆菌科细菌的体内活性评估：在肾盂肾炎和膀胱炎小鼠模型中的评估 Christina Koenig and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2714–2718, 17 Faecal pharmacokinetics, microbiome, and bile acid changes in healthy subjects given intravenous followed by oral omadacycline; a Phase 1 clinical trial 健康受试者静脉注射后口服奥马环素的粪便药代动力学、微生物组和胆汁酸变化：一项1期临床试验 Jinhee Jo and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2719–2726, 18 Interlaboratory comparison of a dried blood spot assay for antiretroviral adherence: implications for clinical application 抗逆转录病毒治疗依从性干血斑检测法的实验室间比对：对临床应用的启示 Nathan Engel and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2727–2731, 19 A multicentre real-life prospective cohort study on effectiveness, durability and safety of long-acting injectable cabotegravir and rilpivirine in northern Italy: the LONGITUDE study 意大利北部长效注射用卡博特韦和利匹韦林有效性、持久性和安全性的现实中多中心前瞻性队列研究：LONGITUDE研究 Maria Mazzitelli and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2732–2741, 20 Assessment of the risk of developing cefepime-induced abnormal liver enzyme levels using the albumin–bilirubin score and fibrosis-4 index: a single-centre retrospective case–control study 使用白蛋白-胆红素评分和纤维化-4指数评估头孢吡肟诱导的肝酶水平异常发生风险：一项单中心回顾性病例对照研究 Hiroki Katsu and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2742–2751, 21 Clinical course of patients with bloodstream infections enrolled in the BALANCE clinical trial BALANCE临床试验中血流感染患者的临床病程 Sean W X Ong and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2752–2758, 22 Comparative outcomes of polymyxins in neurocritical care patients with carbapenem-resistant Gram-negative bacterial pneumonia: a retrospective cohort study 神经重症患者中多黏菌素治疗碳青霉烯类耐药革兰氏阴性菌肺炎的结果比较：一项回顾性队列研究 Qian Zeng and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2759–2772, 23 Distinct population structure and genomic context of NarAB between broiler and human clinical Enterococcus isolates 肉鸡和人类临床分离的粪肠球菌中NarAB的不同群体结构和基因组背景 Jayanth Balakuntla and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2773–2781, 24 Population pharmacokinetics of bictegravir in real-world people with HIV 现实中HIV感染者比克替拉韦的群体药代动力学 Pierre Ekobena and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2782–2789, 25 Rifampicin concentrations throughout the entire treatment duration of active tuberculosis; impact of sex and body mass index 活动性肺结核整个治疗期间利福平浓度：性别和体重指数的影响 Teres Samuelsson and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2790–2798, 26 Performance of disc diffusion and gradient strip test on different Mueller–Hinton agar media plates and ComASP® and Bruker UMIC® Cefiderocol Microdilution Panels for cefiderocol susceptibility testing in carbapenem-resistant Pseudomonas aeruginosa 在碳青霉烯类耐药铜绿假单胞菌中对头孢地尔敏感性测试使用不同穆勒-欣顿琼脂培养基平板和ComASP®及Bruker UMIC®头孢地尔微量稀释板的纸片扩散法和梯度条带测试的性能 Stefano Mancini and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2799–2806, 27 Placental transfer of medications to treat COVID-19, molnupiravir, favipiravir and nirmatrelvir/ritonavir, in the ex vivo human cotyledon model 在离体人类绒毛叶模型中治疗COVID-19的药物莫努匹拉韦、法维拉韦和奈玛特韦/利托那韦的胎盘转移 Solene Labaye and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2807–2813, 28 Synergistic cefiderocol-containing antibiotic combinations active against highly drug-resistant Acinetobacter baumannii patient isolates with diverse resistance mechanisms 针对具有多种耐药机制的高度耐药鲍曼不动杆菌患者分离株的含头孢地尔抗生素联合用药的协同作用 Justin Halim and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2814–2824, 29 Uptake of drug-reduced antiretroviral strategies and impact on costs over 2015–22: experience from an HIV clinic in Paris, France 2015-2022年药物减量抗逆转录病毒策略的采用情况及对成本的影响：来自法国巴黎一家HIV诊所的经验 L Sagaon-Teyssier and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2825–2833, 30 Molecular characterization of fluoroquinolone resistance in invasive clinical isolates of Streptococcus pneumoniae susceptible to delafloxacin 对达拉氟沙星敏感的侵袭性临床肺炎链球菌分离株中氟喹诺酮耐药性的分子特征 Emilia Cercenado and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2834–2843, 31 Genomic structure of class 1 and 2 integrons in non-typhoidal Salmonella isolated from food animals and related meat products in the USA 美国食品动物及其相关肉类产品中分离的非伤寒沙门氏菌1类和2类整合子的基因组结构 Chih-Hao Hsu and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2844–2853, 32 Characterization of blaOXA-542-mediated carbapenem resistance in Acinetobacter baumannii 鲍曼不动杆菌中blaOXA-542介导的碳青霉烯类耐药性的特征 Jingchen Hao and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2854–2861, 33 Phenotypic and genotypic profiles of clinical isolates of various Nocardia species to carbapenems and fluoroquinolones 各种诺卡氏菌属临床分离株对碳青霉烯类和氟喹诺酮类的表型和基因型特征 Jing Yang and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2862–2872, RESEARCH LETTERS（研究快报） 34 Oritavancin in a patient with recurrent endocarditis by Enterococcus faecalis: a new therapeutic option? 奥利他万星治疗粪肠球菌复发性心内膜炎患者：一种新的治疗选择？ Giulia Turicchi and Marco Bongiovanni Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2873–2874, 35 The catA1 chloramphenicol resistance gene originated in Atlantibacter hermannii catA1氯霉素耐药基因起源于大西洋菌属赫尔曼尼菌 Robert A Moran and Ruth M Hall Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2874–2876, 36 Horizontal transmission of a multidrug-resistant IncM1 plasmid harbouring blaOXA-48 and blaCTX-M-14b among patient microbiotas 携带blaOXA-48和blaCTX-M-14b的多重耐药IncM1质粒在患者微生物群中的水平传播 Roberto Sierra and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2876–2879, 37 Antimicrobial activity of temocillin on ceftriaxone-resistant and ceftriaxone-susceptible isolates of Neisseria gonorrhoeae 替莫西林对头孢曲松耐药和头孢曲松敏感淋病奈瑟菌分离株的抗菌活性 Julie Brousseau and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2879–2881, LETTERS TO THE EDITOR（致编辑的信） 38 Comment on: Bactericidal activity of antibiotic combinations against clinical isolates of Enterococcus gallinarum and Enterococcus casseliflavus 述评：抗生素联合用药对临床分离的鸡肠球菌和粪肠球菌的杀菌活性 Karl Oldberg and Magnus Rasmussen Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2882–2883, 39 Comment on: Outcomes of ceftriaxone 2 g versus 1 g daily in hospitalized patients with pneumonia: a nationwide retrospective cohort study 述评：住院肺炎患者每日2克与1克头孢曲松的疗效：一项全国性回顾性队列研究 Giancarlo Ceccarelli and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2884–2885, 40 Outcomes of ceftriaxone 2 g versus 1 g daily in hospitalized patients with pneumonia: a nationwide retrospective cohort study—right to reply—authors’ response 住院肺炎患者每日2克与1克头孢曲松的疗效：一项全国性回顾性队列研究——作者回应权——作者回复 Jumpei Taniguchi and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 10, October 2025, Pages 2885–2886, Journal of Antimicrobial Chemotherapy Volume 80, Issue Supplement_4抗菌化疗杂志 80卷增刊4期 https://academic.oup.com/jac/issue/80/Supplement_4 SUPPLEMENT（补充） Two Decades of BSAC Resistance Surveillance 英国抗菌化疗学会二十年耐药性监测 FOREWORD（前言） 1 Two Decades of BSAC Resistance Surveillance 英国抗菌化疗学会二十年耐药性监测 James C Hurley and Alan P Johnson Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_4, October 2025, Page iv1, SUPPLEMENT PAPERS（补充论文） 2 Two decades of resistance surveillance by the British Society for Antimicrobial Chemotherapy: design, development, delivery, deficiencies and future directions 英国抗菌化疗学会二十年耐药性监测：设计、发展、实施、不足与未来方向 Alasdair P MacGowan and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_4, October 2025, Pages iv2–iv6, 3 The British Society for Antimicrobial Chemotherapy Resistance Surveillance Project: methods and limitations 英国抗菌化疗学会耐药性监测项目：方法与局限性 Michael Allen and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_4, October 2025, Pages iv7–iv21, 4 Antimicrobial resistance among Gram-positive agents of bacteraemia in the UK and Ireland: trends from 2001 to 2019 英国和爱尔兰地区革兰氏阳性菌血流感染病原体的抗菌药物耐药性趋势（2001 - 2019年） Rosy Reynolds and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_4, October 2025, Pages iv22–iv35, 5 Antimicrobial resistance among Gram-negative agents of bacteraemia in the UK and Ireland: trends from 2001 to 2019 英国和爱尔兰地区革兰氏阴性菌血流感染病原体的抗菌药物耐药性趋势（2001 - 2019年） Rosy Reynolds and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_4, October 2025, Pages iv36–iv48, 6 Antimicrobial resistance among agents of hospital-acquired lower respiratory tract infection in the UK and Ireland: trends from 2008/2009 to 2018/2019 英国和爱尔兰地区医院获得性下呼吸道感染病原体的抗菌药物耐药性趋势（2008/2009 - 2018/2019年） Rosy Reynolds and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_4, October 2025, Pages iv49–iv59, 7 Antimicrobial resistance among agents of community-associated lower respiratory tract infection in the UK and Ireland: trends from 1999/2000 to 2018/2019 英国和爱尔兰地区社区获得性下呼吸道感染病原体的抗菌药物耐药性趋势（1999/2000 - 2018/2019年） Rosy Reynolds and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_4, October 2025, Pages iv60–iv71, 8 Trends of serotypes and resistance among Streptococcus pneumoniae in the UK and Ireland (1999–2019) 英国和爱尔兰地区肺炎链球菌血清型及耐药性趋势（1999 - 2019年） Carolyne Horner and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_4, October 2025, Pages iv72–iv86, 9 Applications and benefits of the British Society for Antimicrobial Chemotherapy Resistance Surveillance Project—legacy and future 英国抗菌化疗学会耐药性监测项目的应用与益处——成果与未来 Benjamin J Parcell and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue Supplement_4, October 2025, Pages iv87–iv95, Journal of Antimicrobial Chemotherapy Volume 80, Issue 11抗菌化疗杂志 80卷 11期 https://academic.oup.com/jac/issue VIEWPOINTS（观点） 1 Modification of antimicrobial susceptibility testing methods 抗菌药物敏感性检测方法的修改 Ian Morrissey and Jean B Patel Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2887–2888, 2 Viewpoint: global antimicrobial stewardship accreditation is needed: the experience in Kentucky, USA 观点：需要建立全球抗菌药物管理认证体系：美国肯塔基州的经验 Ashley M Wilde and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2889–2891, REVIEWS（综述） 3 Phages connect the biological dots of antimicrobial resistance: from genesis and spread to alternative treatment modules 噬菌体揭示抗菌药物耐药性的生物学脉络：从起源与传播到替代治疗模式 Cleo Anastassopoulou and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2892–2901, 4 Molecular drivers of fusion plasmid: mechanistic insights and evolutionary implications 融合质粒的分子驱动因素：机制见解与进化意义 Ziyi Liu and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2902–2911, ORIGINAL RESEARCH（研究论著） 5 Emergence of livestock-associated MRSA clonal complex 398 in Thailand’s swine industry 泰国养猪业中出现与牲畜相关的MRSA克隆复合体398 Pawarut Narongpun and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2912–2917, 6 Peripheral neuropathy during long-term suppressive therapy with tedizolid: a case series 长期使用替达拉韦抑制治疗期间出现周围神经病变：系列病例报告 Tomaso Beringheli and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2918–2922, 7 Low bacterial metabolism as a central mechanism of antimicrobial resistance and potential therapeutic target of staphylococcal biofilms in ventricular assist device driveline infections 细菌低代谢作为抗菌药物耐药性的核心机制及心室辅助装置驱动线感染中葡萄球菌生物膜的潜在治疗靶点 Yao Sun and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2923–2933, 8 The pivotal role of acnA in linking carbon metabolism to virulence and antimicrobial resistance in methicillin-resistant Staphylococcus aureus acnA在连接碳代谢与耐甲氧西林金黄色葡萄球菌的毒力和抗菌药物耐药性中的关键作用 Jiahui Li and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2934–2944, 9 Pharmacokinetics of rifampicin and isoniazid in patients with HIV–tuberculosis coinfection receiving efavirenz-based antiretroviral treatment: an ANRS12292–RIFAVIRENZ sub-study 接受以依非韦伦为基础的抗逆转录病毒治疗的HIV-结核病共感染患者中利福平和异烟肼的药代动力学：ANRS12292-RIFAVIRENZ子研究 Thibaut Gelé and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2945–2953, 10 Novel mutations associated with clofazimine resistance in Mycobacterium intracellulare 胞内分枝杆菌中与氯法齐明耐药相关的新型突变 Xiuzhi Jiang and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2954–2957, 11 Physiologically informed in vitro framework reveals context-dependent combinatory activity of niclosamide–colistin against Gram-negative bacteria 基于生理信息的体外框架揭示了针对革兰氏阴性菌的硝基咪唑-多粘菌素组合的情境依赖性活性 Mariana Romero-Gonzalez and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2958–2969, 12 In vitro evolution provides insights into mechanisms of Mycoplasma genitalium resistance to moxifloxacin 体外进化揭示生殖支原体对莫西沙星的耐药机制 Teck-Phui Chua and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2970–2977, 13 The toxin–antitoxin system SavRS contributes to vancomycin resistance in vancomycin-intermediate Staphylococcus aureus by mediating cell wall thickening 毒素-抗毒素系统SavRS通过介导细胞壁增厚促进万古霉素中间型金黄色葡萄球菌对万古霉素的耐药性 Weifeng Xu and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2978–2988, 14 Molecular insights into carbapenemase-producing Enterobacterales from Senegal 塞内加尔产碳青霉烯酶肠杆菌目细菌的分子特征 Ousmane Sow and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 2989–3000, 15 Population pharmacokinetic model of linezolid and its metabolite PNU-142300 in elderly patients 老年患者中利奈唑胺及其代谢产物PNU-142300的群体药代动力学模型 Xianglong Chen and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3001–3010, 16 In vitro activity of contezolid and other comparators against clinical Staphylococcus and Enterococcus: a multicenter study in China 在中国开展的一项多中心研究中，康替唑胺及其他对照药物对临床分离的金黄色葡萄球菌和肠球菌的体外活性 Rongqi Lu and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3011–3020, 17 Co-existence of the oxazolidinone resistance genes cfr and optrA on a novel multiresistance plasmid from a methicillin-resistant Macrococcoides bohemicum strain 从一株耐甲氧西林的马科考代菌属波希米亚菌株中发现的携带恶唑烷酮耐药基因cfr和optrA的新型多重耐药质粒 Yao Zhu and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3021–3025, 18 Multidrug resistance and recurrence in urinary bacteraemia among cancer patients 癌症患者中尿路菌血症的多药耐药性和复发情况 Ignacio Grafia and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3026–3033, 19 Rapid replacement of blaKPC variant in ST11 carbapenem-resistant and hypervirulent Klebsiella pneumoniae contributed to ceftazidime/avibactam resistance during severe in vivo infection 在严重的体内感染期间，ST11型碳青霉烯耐药且高毒力的肺炎克雷伯菌中blaKPC变体的快速替代导致头孢他啶/阿维巴坦耐药 Ping Yang and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3034–3042, 20 Potential human health risk of carbapenem-non-susceptible Pseudomonas aeruginosa from companion animals 伴侣动物中碳青霉烯类不敏感铜绿假单胞菌对人类健康的潜在风险 Jirachaya Toyting-Hiraishi and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3043–3056, 21 Assessment of an LC coupled with tandem MS (LC-MS/MS) tool in the detection of antimicrobial resistance mechanisms in Enterobacterales 液相色谱-串联质谱（LC-MS/MS）工具在检测肠杆菌目细菌抗菌药物耐药机制中的应用评估 Anna Witkowska and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3057–3064, 22 Multidrug efflux pumps and innate azole resistance of Mucor lusitanicus 毛霉属葡萄牙菌的多药外排泵及其固有唑类耐药性 Stephanie Toepfer and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3065–3078, 23 Ivermectin dosing for children under 2 years 2岁以下儿童的伊维菌素剂量 Wenyu Yang and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3079–3081, 24 Effectiveness of first-line lamivudine/dolutegravir antiretroviral therapy in persons with HIV: real-life data from the ICONA Foundation cohort 一线拉米夫定/多替拉韦抗逆转录病毒疗法在HIV感染者中的有效性：来自ICONA基金会队列的现实数据 Alessandra Vergori and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3082–3091, 25 Eligibility and factors associated with long-acting injectable cabotegravir-rilpivirine initiation in an urban academic HIV clinic 城市学术型HIV诊所中长效注射用卡博特韦-利匹韦林启动的资格及关联因素 Geoffroy Liegeon and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3092–3100, 26 Evaluation of HIV-1 DNA resistance evolution in highly treatment-experienced and multi-resistant individuals under suppressive antiretroviral therapy: a longitudinal study from the PRESTIGIO Registry 在接受抑制性抗逆转录病毒治疗的高度治疗经验丰富和多药耐药个体中，HIV-1 DNA耐药演变的评估：来自PRESTIGIO登记处的纵向研究 D Armenia and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3101–3106, 27 Sequential antibiotic exposure restores antibiotic susceptibility 序贯抗生素暴露恢复抗生素敏感性 Farhan R Chowdhury and Brandon L Findlay Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3107–3117, 28 Dermatological adverse effects of doxycycline as post-exposure prophylaxis for sexually transmitted infections among men who have sex with men: real-world findings from a multicentre study 在男男性行为者中，使用多西环素作为性传播感染暴露后预防的皮肤科不良反应：一项多中心研究的现实发现 Ling-Ya Chen and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3118–3122, 29 Phenotype–genotype discordance in antimicrobial resistance profiles of Gram-negative uropathogens recovered from catheter-associated urinary tract infections in Egypt 埃及导管相关尿路感染中分离的革兰氏阴性尿路病原菌抗菌药物耐药性表型-基因型不一致性 Mohamed Eladawy and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3123–3132, 30 How should APOBEC3-induced resistance mutations be considered in the management of antiretroviral therapy? 在抗逆转录病毒治疗管理中，应如何考虑APOBEC3诱导的耐药突变？ Marie Gilbert and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3133–3138, 31 In vitro evaluation of olorofim and antifungal combinations against Aspergillus and Candida species 奥洛芬和抗真菌药物组合对曲霉菌和念珠菌属的体外评价 Corinne Pinder and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3139–3149, 32 Antagonistic interaction between posaconazole and olorofim in a murine model of invasive pulmonary aspergillosis 在侵袭性肺曲霉病小鼠模型中，泊沙康唑与奥洛芬之间的拮抗作用 Christopher A Darlow and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3150–3159, 33 High level of archived and circulating HIV-1 drug resistance mutations in adolescents with a detectable viremia in Cameroon 喀麦隆可检测到病毒载量的青少年中HIV-1药物耐药突变的存档和循环水平较高 Armando B D Djiyou and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3160–3164, RESEARCH LETTERS（研究快讯） 34 SCY-247, a novel second-generation triterpenoid antifungal, demonstrates high in vitro activity against genetically diverse Candida auris isolates, including FKS1 mutants 新型第二代三萜类抗真菌药物SCY-247对包括FKS1突变体在内的多种基因型耳道假丝酵母菌显示出高体外活性 Bram Spruijtenburg and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3165–3166, 35 Drug–drug interactions between tirzepatide and antiretrovirals: time to reassess and reassure? 替西帕肽与抗逆转录病毒药物之间的药物-药物相互作用：是时候重新评估和安心了吗？ Andrea Poloni and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3167–3168, 36 Does the use of topical azoles have an impact on antifungal resistance? 局部使用唑类药物对抗真菌耐药性有影响吗？ Jean-Yves Maillard Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3168–3186, 37 Leakage of cabotegravir and rilpivirine in HIV patients receiving long-acting injectable antiretroviral therapy 接受长效注射用抗逆转录病毒治疗的HIV患者中卡博特韦和利匹韦林的泄漏情况 Samir Benkouiten and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Pages 3187–3188, CORRECTION（更正） 38 Correction to: Clinical and microbiological analysis of bloodstream infections by four cefiderocol-resistant and not previously exposed NDM-producing Klebsiella pneumoniae 更正：对四种产NDM且之前未接触过头孢地洛的耐药肺炎克雷伯菌引起的血流感染的临床和微生物学分析 Journal of Antimicrobial Chemotherapy, Volume 80, Issue 11, November 2025, Page 3189, Journal of Antimicrobial Chemotherapy Volume 80, Issue 12抗菌化疗杂志 80卷 12期 https://academic.oup.com/jac/issue VIEWPOINT（观点） 1 Rifampicin as monotherapy for infections caused by Staphylococcus aureus: considerations for not applying ‘breakpoints in brackets’ 利福平单药治疗金黄色葡萄球菌感染：关于不应用“括号内折点”的考量 Sara E Boyd and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3191–3193, REVIEWS（综述） 2 The Achilles’ heel of the Trojan Horse? A systematic evaluation of cefiderocol susceptibility testing 特洛伊木马的致命弱点？头孢地尔药敏试验的系统评价 Deny Tsakri and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3194–3207, 3 Antifungal treatment strategies and their impact on resistance development in clinical settings 抗真菌治疗策略及其对临床环境中耐药性发展的影响 Norman Van Rhijn and P Lewis White Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3208–3226, ORIGINAL RESEARCH（论著） 4 Decrease in colistin resistance among young bovine and pig productions in France: relationship with colistin usage and stewardship measures 法国年轻牛和猪生产中多粘菌素耐药性的下降：与多粘菌素使用及管理措施的关系 Claire Chauvin and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3227–3235, 5 Time to anti-cancer treatment resumption after SARS-CoV-2 infection in patients with active haematological diseases undergoing combined antiviral treatments 接受联合抗病毒治疗的活动性血液系统疾病患者感染SARS-CoV-2后恢复抗癌治疗的时间 E Matteini and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3236–3241, 6 From TRIO to one: simplification to bictegravir/emtricitabine/tenofovir alafenamide in highly treatment-experienced people living with MDR HIV 从三联疗法到单一疗法：在多重耐药HIV感染且治疗经验丰富的人群中简化使用比克替拉韦/恩曲他滨/丙酚替诺福韦 José L Casado and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3242–3247, 7 Effects of commonly used antibiotics on children’s developing gut microbiomes and resistomes in peri-urban Lima, Peru 秘鲁利马市郊常用抗生素对儿童发育中的肠道微生物组和耐药组的影响 Neha Sehgal and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3248–3256, 8 Frailty Index Laboratory (FI-Lab) as predictor of poor outcomes for intra-hospital multidrug-resistant Klebsiella pneumoniae bloodstream infections: a single-centre retrospective cohort study 衰弱指数实验室（FI-Lab）作为预测院内多重耐药肺炎克雷伯菌血流感染不良预后的指标：一项单中心回顾性队列研究 Carmen Pellegrino and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3257–3264, 9 Mechanisms of resistance to ceftazidime/avibactam in mutants derived in vitro from Klebsiella pneumoniae producing OXA-48-like enzymes 体外衍生的产OXA-48样酶肺炎克雷伯菌突变体对头孢他啶/阿维巴坦的耐药机制 T Blanco-Martín and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3265–3272, 10 Comparative evaluation of disc diffusion and broth microdilution methods for aztreonam/avibactam susceptibility testing in Enterobacterales 肠杆菌目中氨曲南/阿维巴坦药敏试验的纸片扩散法和肉汤微量稀释法的比较评价 Ioannis Baltas and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3273–3277, 11 Efficacy of topical hydrophilic gel of paromomycin combined with systemic or locally administered leishmanicidal drugs for treatment of experimental leishmaniasis caused by Leishmania (Viannia) braziliensis 硫酸巴龙霉素亲水性凝胶局部用药联合全身或局部使用杀利什曼原虫药物治疗巴西利什曼原虫（Viannia亚属）引起的实验性利什曼病的疗效 Líndicy Leidicy Alves and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3278–3287, 12 Population pharmacokinetics and dosing optimization of cefoselis in paediatric patients with haematological malignancies 血液系统恶性肿瘤患儿中头孢噻利的群体药代动力学及剂量优化 Jing-Rui Liu and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3288–3296, 13 Therapeutic challenges in treating ESBL- and/or AmpC-producing non-carbapenemase-producing Enterobacterales: an in vitro evaluation of novel β-lactam/β-lactamase inhibitor combinations and cefiderocol 治疗产超广谱β-内酰胺酶（ESBL）和/或AmpC酶且不产碳青霉烯酶的肠杆菌目细菌的挑战：新型β-内酰胺/β-内酰胺酶抑制剂组合和头孢地尔的体外评价 Inès Rezzoug and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3297–3305, 14 Post-exposure prophylaxis with doxycycline (DoxyPEP) to prevent STIs in a real-world setting: the PRIDOX study 使用多西环素进行暴露后预防（DoxyPEP）以在现实环境中预防性传播感染：PRIDOX研究 R Palacios and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3306–3310, 15 Risk–benefit balance of blood cultures among patients with stage IV cancer in unplanned admission: a nationwide propensity score–weighted study in Japan 日本全国范围内倾向评分加权研究：IV期癌症患者非计划入院时血培养的风险-获益平衡 Yuki Hashimoto and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3311–3319, 16 A drug-repurposing screen of FDA- and EMA-approved drugs identifies two NF-κB inhibitors active against eumycetoma 对美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准的药物进行药物再利用筛选，发现两种对真性着色真菌病有活性的NF-κB抑制剂 Jingyi Ma and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3320–3328, 17 Temocillin versus other intravenous beta-lactams for urinary tract infections caused by third-generation cephalosporin-resistant Enterobacterales: a multicentre retrospective matched cohort study 替莫西林与其他静脉注射β-内酰胺类药物治疗第三代头孢菌素耐药肠杆菌目引起的尿路感染：一项多中心回顾性匹配队列研究 Jeanne Iachkine and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3329–3334, 18 Treatment preferences by infectious diseases clinicians for carbapenem-resistant Enterobacterales infections 感染科医生对碳青霉烯耐药肠杆菌目感染的治疗偏好 Samuel E Cincotta and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3335–3339, 19 The aphA1 kanamycin and neomycin resistance gene originated in Klebsiella michiganensis aphA1卡那霉素和新霉素耐药基因起源于密歇根克雷伯菌 Robert A Moran and Ruth M Hall Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3340–3344, 20 Global susceptibility profiles and potential resistance mechanisms of ceftazidime–avibactam-resistant, non-carbapenemase-producing carbapenem-resistant Enterobacterales: 2020–23 data from the Antimicrobial Testing Leadership and Surveillance 头孢他啶-阿维巴坦耐药且不产碳青霉烯酶的碳青霉烯耐药肠杆菌目的全球易感性特征和潜在耐药机制：2020-2023年来自抗菌药物测试领导与监测的数据 Chih-Cheng Lai and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3345–3351, 21 Comparative in vitro activity of ceftazidime-avibactam plus aztreonam and the fixed combination aztreonam/avibactam against multidrug-resistant Pseudomonas aeruginosa 头孢他啶-阿维巴坦联合氨曲南与固定组合氨曲南/阿维巴坦对多重耐药铜绿假单胞菌的体外活性比较 Sophie E Müller and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3352–3356, 22 Dual β-lactam synergy in Enterococcus faecalis and its relationship with penicillin-ceftriaxone infective endocarditis treatment outcomes 粪肠球菌中双重β-内酰胺协同作用及其与青霉素-头孢曲松感染性心内膜炎治疗结果的关系 April Gregson and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3357–3366, 23 The long walk to a short half-life: the discovery of augmented renal clearance and its impact on antibiotic dosing 走向短半衰期的漫长之路：发现肾增强清除及其对抗菌药物剂量调整的影响 Jeffrey Lipman and Russell E Lewis Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3367–3374, 24 Aztreonam-amoxicillin/clavulanate combination therapy against blaNDM-producing Enterobacterales infections 氨曲南-阿莫西林/克拉维酸联合治疗产blaNDM肠杆菌目感染 Efrat Orenbuch-Harroch and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3375–3380, 25 Evaluation of sodium zirconium cyclosilicate usage for hyperkalaemia secondary to sulfamethoxazole/trimethoprim therapy 评估锆酸钠环硅酸盐用于磺胺甲恶唑/甲氧苄啶治疗继发的高钾血症 Dixie Pyles and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3381–3385, 26 Thrice-weekly post-haemodialysis ceftazidime can achieve adequate pre-dialysis concentrations and clinical cure in patients with melioidosis 每周三次血液透析后使用头孢他啶可在类鼻疽患者中达到足够的透析前浓度并实现临床治愈 Simon Smith and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3386–3390, 27 In vitro and clinical data demonstrate negligible risk of drug–drug interactions with opelconazole, a novel inhaled antifungal agent 体外和临床数据表明，新型吸入抗真菌药物奥培康唑的药物-药物相互作用风险可忽略不计 Lindsey M R Cass and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3391–3400, 28 Antifungal prophylaxis in patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)–positive acute myeloid leukaemia receiving sorafenib during initial induction and consolidation treatment in ALLG AMLM16 trial 在ALLG AMLM16试验中，FLT3-ITD阳性急性髓系白血病患者在初始诱导和巩固治疗期间接受索拉非尼治疗时的抗真菌预防 Chin Fen Neoh and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3401–3406, 29 The synergistic activity of tigecycline-based combinations against multidrug-resistant Acinetobacter baumannii-caused bloodstream infections 基于替加环素的联合用药对多重耐药鲍曼不动杆菌引起的血流感染的协同活性 Huan Zhang and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3407–3418, 30 Piperacillin dosing in pediatric patients and augmented renal clearance: are current guidelines sufficient to achieve therapeutic concentration coverage? 儿科患者中哌拉西林的剂量调整与肾增强清除：现行指南是否足以达到治疗浓度覆盖？ Anne Ravix and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3419–3430, 31 Efficacy of human-simulated aztreonam-avibactam against Stenotrophomonas maltophilia in the neutropenic murine thigh infection model 在中性粒细胞减少的小鼠大腿感染模型中评估人模拟氨曲南-阿维巴坦对嗜麦芽窄食单胞菌的疗效 Yakun Fu and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3431–3437, 32 A prospective assessment of the efficacy and durability of long-acting cabotegravir and rilpivirine in individuals with HIV in Spain (RELATIVITY study) 西班牙HIV感染者长期使用卡博特韦和利匹韦林的有效性和持久性的前瞻性评估（RELATIVITY研究） Luis Buzón-Martín and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3438–3451, 33 Antagonistic in vitro interaction between olorofim and voriconazole against Aspergillus fumigatus 奥洛罗芬和伏立康唑对烟曲霉的体外拮抗作用 Illan Laloum and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3452–3461, RESEARCH LETTERS（研究快讯） 34 Concomitant IV vancomycin causing delayed high-dose methotrexate clearance and acute kidney injury 静脉注射万古霉素联用导致大剂量甲氨蝶呤清除延迟和急性肾损伤 Thao Dao and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3462–3464, 35 Overestimation of piperacillin/tazobactam resistance in Escherichia coli by disc diffusion and gradient strip methods 纸片扩散法和梯度条法高估大肠埃希菌对哌拉西林/他唑巴坦的耐药性 Stefano Mancini and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3464–3467, 36 Mind the gap: missed re-initiation and monitoring in statin–antimicrobial co-prescriptions 注意差距：他汀类药物与抗菌药物联合处方中的漏重新起始和监测 Melwin Kyle Solis and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3467–3468, 37 Pharmacokinetics of aztreonam/avibactam in a critically ill patient with a class B metallo-β-lactamase producing Enterobacteriaceae and receiving continuous renal replacement therapy 一名接受连续肾脏替代治疗且感染产B类金属β-内酰胺酶肠杆菌科细菌的重症患者中氨曲南/阿维巴坦的药代动力学 Daniel Fresán and others Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3469–3471, CORRECTION（更正） 38 Correction to: Systematic reviews and the Journal of Antimicrobial Chemotherapy; past, present and future. A systematic reappraisal 更正：系统评价与《抗菌药物化疗杂志》：过去、现在和未来。一项系统再评价 Journal of Antimicrobial Chemotherapy, Volume 80, Issue 12, December 2025, Pages 3472–3473,

2025-11-29

·启示与生活

黑热病研究进展

贾玉琦1冯旭飞2白雪兵2李雁笛2姚添2张沛刚1王素萍2陈靖3冯永亮2 1山西医科大学临床学科建设中心，晋中030600；2山西医科大学公共卫生学院，太原030001；3山西省疾病预防控制中心，太原033001 通信作者：冯永亮，Email：yongliang.feng＠sxmu.edu.Cn 【摘要】黑热病（内脏利什曼病）是由杜氏利什曼原虫或婴儿利什曼原虫引起的经白蛉传播的人兽共患寄生虫病，近年来在我国部分地区呈现回归性流行趋势，对公共卫生构成严重威胁。现全面梳理黑热病的病原学、流行病学特征、发病机制、诊断技术及治疗的最新研究进展，以期为黑热病的有效防控提供参考。【关键词】诊断；内脏利什曼病；利什曼原虫；流行特征；免疫逃逸黑热病［又称为内脏利什曼病（visceral leishmaniasis，VL）］是一种由利什曼原虫（Leishmania spp.）引起的人兽共患寄生虫病［1］。近年来，VL在我国部分地区逐渐呈现回归性流行趋势［2］，严重威胁公共卫生安全。现系统梳理利什曼原虫的病原学、流行病学、发病机制、诊断技术及治疗的最新研究，以期提升临床对本病的早期识别与防控能力。一、病原学利什曼原虫属锥虫科（Trypanosomatidae）利什曼属（Leishmania），引起VL的病原体主要为杜氏利什曼原虫（Leishmania donovani）与婴儿利什曼原虫（Leishmania infantum Noicolle）［3］。其生活史包括前鞭毛体（promastigote）和无鞭毛体（amastigote）两个时期，前鞭毛体是杜氏利什曼原虫的感染阶段，寄生于节肢动物（白蛉）的消化道内，呈梭形，大小为（14.3～20）μm×（1.5～1.8）μm，具单根游离鞭毛［4］，在37℃酸性环境刺激下，数小时内即可转化为无鞭毛体［5］；无鞭毛体是杜氏利什曼原虫的致病阶段，寄生于人或哺乳动物的单核巨噬细胞内，呈卵圆形，大小为（2.9～5.7）μm×（1.8～4.0）μm［4］，其生活史见图1。传统观点认为利什曼原虫以无性繁殖为主，但近年研究表明其可在媒介白蛉体内进行隐性有性生殖。2023年Riyal等［6］首次在自然媒介银足白蛉（Phlebotomus argentipes）体内成功实现杜氏利什曼原虫皮肤株与内脏株的实验性遗传杂交（检出率约3％），该研究揭示了自然媒介中种内杂交可成为新致病株出现的潜在途径。此外，印度研究人员发现了一株引发皮肤利什曼病（cutaneous leishmaniasis，CL）的非杂交型杜氏利什曼原虫ISC1 Yeti进化支（杂合指数＜0.17），该进化支兼具致VL与CL的双重能力，揭示同一遗传谱系可介导不同组织嗜性［7］。鉴于CL患者可能成为VL传播的潜在储存宿主，亟需将皮肤型病例纳入VL消除计划的监测体系。二、流行病学特征全球VL的流行具有显著的地域聚集性与人群特异性，主要可分为人源型（人与人传播）和动物源型（动物向人传播）。人源型VL的传染源为患者及无症状感染者，主要流行于印度次大陆、东非和巴西，青少年与成人多见；动物源型VL以犬类及野生动物为传染源，主要分布于地中海地区、南美洲及中国西部，儿童、免疫功能低下者（尤其是HIV感染者）及营养不良者构成主要高危人群［8-9］。值得注意的是，地中海地区因HIV-VL（HIV与利什曼原虫的合并感染）发病率较高而成为特殊的流行区域［9-10］。两类VL均通过白蛉叮咬传播。我国VL具有类型多样、区域分布明确的特点，根据传染源差异可分为3类。①人源型（平原型）：流行于华北平原及新疆维吾尔自治区南部绿洲地区。传染源为患者，传播媒介为家栖或近家栖的中华白蛉与长管白蛉。人群普遍易感，儿童发病率较高［1］。②犬源型（山丘型）：集中分布于甘肃省、四川省等山区。传染源为病犬，传播媒介为野栖或近野栖的中华白蛉。患者中10岁及以下的儿童占58.1％，成人很少感染［11］。③野生动物型（荒漠型）：见于新疆维吾尔自治区、内蒙古自治区荒漠地区。传染源为狼、狐等野生动物，传播媒介为野栖型吴氏白蛉与亚历山大白蛉。2岁以下婴幼儿为高发人群（在新疆维吾尔自治区，2岁以下婴幼儿患者占92％）［12］。此外，环境与社会对VL的传播与扩散起关键作用。①环境因素：全球变暖、降雨波动、森林砍伐与城市化等生态变化可影响白蛉密度与宿主分布，驱动疫源地变迁。②社会因素：社会经济落后、居住条件差、露宿习惯、饲养犬类、战争冲突及人口流动等因素显著增加了人群与媒介的接触机会，从而增加感染风险［5-6］。在时间分布上，VL在全球多呈全年散发态势。然而由于白蛉繁殖与活动受温度制约，通常在气温回升后进入活跃期。因此，中国的年度发病高峰多集中于4月［2］。值得注意的是，近年来我国西部地区（如甘肃省、新疆维吾尔自治区、四川省）的VL报告病例数呈现下降趋势，此现象被认为与脱贫攻坚、生活条件改善及人居环境整治等积极的社会经济因素密切相关［13］。三、致病机制病原体侵入宿主是建立感染并引发疾病的先决条件。利什曼原虫感染宿主的致病机制见图2。（一）利什曼原虫的侵入（前鞭毛体阶段）当感染性前鞭毛体通过白蛉叮咬注入宿主后，其表面分子［如脂磷酸聚糖（lipophosphoglycan，LPG）］直接抑制还原型烟酰胺腺嘌呤二核苷酸磷酸（reduced nicotinamide adenine dinucleotide phosphate，NADPH）氧化酶在吞噬体膜上的组装，从而规避呼吸爆发导致的活性氧和一氧化氮产生，显著提升原虫在巨噬细胞内的初始存活率［14］。（二）胞内存活与定植（无鞭毛体阶段）寄生虫进入巨噬细胞并转化为无鞭毛体，则开始抵抗宿主的溶酶体杀伤：无鞭毛体利用其主要的表面分子LPG抑制宿主蛋白Ras相关蛋白Rab-7a（Ras-related protein Rab-7a，Rab7）（介导内吞体-溶酶体融合）在内吞体上的募集，阻断了内吞体与溶酶体的融合；同时，LPG改变吞噬体膜脂质流动性，直接抑制液泡型ATP酶（vacuolar-type H＋-translocating adenosine triphosphatase，V-ATPase）的质子泵（负责酸化吞噬体）活性，以维持吞噬体的中性pH环境［15］，促进其生存和繁殖。（三）免疫逃逸的分子机制当机体感染利什曼原虫后，其表面的LPG分子可激活Toll样受体2及4介导的髓样分化因子88/核因子κB（Toll-like receptor 2/4-myeloid differentiation primary response 88/nuclear factor kappa-light-chain-enhancer of activated B cells，TLR2/4-MyD88/NF-κB）信号通路［16］，诱导IL-1β等炎症因子的释放，为DC激活与抗原呈递功能的发挥提供炎性环境，进而启动以Th1为主的保护性免疫应答，以清除病原体［17-18］。然而，利什曼原虫可通过多途径实现免疫逃逸：①显著抑制IκB激酶β（IκB kinase beta，IKKβ）磷酸化来削弱核因子κB活化，从而干扰炎症反应的启动［19］；②阻断核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3（nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3，NLRP3）炎症小体的组装，导致IL-1β的分泌明显减少［14］；③下调主要组织相容性复合体Ⅱ类分子（major histocompatibility comple class Ⅱ，MHC-Ⅱ）表达量，阻碍T细胞的有效识别［20］；④在感染部位（如脾脏）诱导Treg的扩增，这些细胞分泌的IL-10等因子可抑制巨噬细胞的杀菌功能［21］。因此，开发或应用靶向小分子药物是逆转利什曼原虫免疫逃逸的主要手段，例如IKKβ激动剂、NLRP3激活剂、Ⅱ类反式激活因子（class Ⅱ trans-activator，CⅡTA）表达激活剂，以及Treg耗竭剂（抗CD25抗体）等。综上所述，利什曼原虫侵入宿主机体后表面分子LPG通过与宿主因子相互作用逃避宿主免疫系统的清除作用，然而当微量病原体感染后，宿主哪些免疫细胞或免疫因子发挥限制和清除作用，以及如何发挥作用有待进一步深入研究。（四）病理损伤的级联反应 1.脾脏损伤：寄生虫感染导致脾脏内Treg扩增和TGF-β分泌，形成免疫抑制性微环境，导致巨噬细胞功能障碍及脾纤维化和肿大（达正常重量的10倍）［22］。早期联合抗纤维化药物与抗原虫治疗有助于缓解免疫损伤。 2.骨髓损伤：骨髓内寄生的原虫破坏造血微环境，导致CD34＋造血干细胞减少，粒-单核系祖细胞集落形成率下降［23］。骨髓损伤可直接导致粒细胞缺乏、贫血、血小板减少三联征，从而引起继发感染、红细胞生成不足及出血倾向［23］。治疗上可应用粒细胞集落刺激因子（granulocyte colony stimulating factor，G-CSF）、促红细胞生成素（erythropoietin，EPO）等造血因子，并探索抗氧化剂等保护造血微环境的干预手段。 3.铁代谢障碍：慢性感染可致铁调素（hepcidin）升高，抑制铁释放。该过程叠加原虫掠夺铁和溶血致铁滞留，最终引发血清铁及转铁蛋白饱和度降低的重度铁代谢障碍［24］。因此，应在控制感染的基础上，谨慎补充静脉铁剂（避免促进原虫生长），并结合铁调素拮抗剂改善铁代谢。四、诊断技术 VL的诊断以流行病学史和临床表现为基础，确诊需依赖血清学检测、病原体镜检或分子生物学检测。我国现行诊断标准为《黑热病诊断标准：WS258-2006》［25］；WHO则根据不同流行区域的特点发布针对性技术指南［26-27］。传统诊断方法如骨髓镜检和rK39抗体快速检测仍是流行地区的主要手段，但由于前者侵入性强、后者假阳性率较高，在临床应用中存在一定局限性。近年来，基于分子水平的新型方法不断发展，如定量聚合酶链反应（quantitative polymerase chain reaction，qPCR）、环介导等温扩增技术（loop mediated isothermal amplification，LAMP）和宏基因组学二代测序（metagenomic next-generation sequencing，mNGS）等，均显示出良好的应用前景。（一）病原学诊断 1.涂片镜检：通过穿刺骨髓、脾脏或淋巴结获取样本，经吉姆萨染色后镜检寻找无鞭毛体。其中，骨髓穿刺灵敏度约为60％～85％，脾穿刺灵敏度＞95％，但伴随较大出血风险，不建议使用［28］。 2.原虫培养：诊断利什曼病的金标准，常用三恩培养基（Novy-McNeal-Nicolle medium）培养血液或骨髓穿刺液（22～25℃，7～10d，高度疑似者延至4周）；该方法灵敏度高但耗时长。可用Schneider培养基缩短培养时间［1，29］。（二）血清学检测 1.直接凝集试验（direct agglutination test，DAT）：基于抗原-抗体凝集反应，操作简便且成本效益高。一项纳入78项研究的荟萃分析显示其灵敏度为95％（95％CI 90％～98％），特异度为95％（95％CI 88％～98％）［30］，缺点是可能与其他病原体抗原存在交叉反应［31］。改进的快速凝集法灵敏度为95.4％，特异度为88.5％，更适于大规模筛查［32］。 2.免疫层析试纸诊断技术：美国InBios公司生产的以重组蛋白rK39为包被抗原的免疫层析试纸条被广泛推荐，是全球内脏利什曼病流行地区最常用的快速诊断手段。多个国家的临床验证结果显示其灵敏度可达95％以上，特异度达90％以上［33］。但该产品价格高昂，对VL多发的贫困地区患者极不友好，不利于大面积推广使用。国产rK39（北京万泰生物药业股份有限公司）诊断试纸条价格较低，但灵敏度和特异度也相对较低，操作快速简便（15～20 min），适用于基层医疗卫生机构（如卫生室、社区中心）的VL初筛，且需结合临床表现来确诊［34］。近年来，rK26蛋白（也被称为亲水性酰化表面蛋白B，存在于前鞭毛体和无鞭毛体的质膜上）成为新兴诊断靶标。石锋等［35］基于利什曼原虫K26重组抗原建立了快速检测VL特异抗体的胶体金免疫层析试纸条方法，临床检测结果表明其灵敏度（91.82％）和特异度（100％）与美国InBios公司的rK39试纸条（灵敏度为93.64％，特异度为100％）之间差异无统计学意义。然而，K26编码基因具有虫株特异性：同一流行区虫株的K26基因高度保守，而不同流行区虫株间存在显著差异。由于这种差异可能导致抗体检测灵敏度下降，所以需制备基于本地分离株的K26抗原，以确保诊断的准确性。 3.ELISA：ELISA是一种广泛应用于包括利什曼病在内的几乎所有传染病的诊断方法。近年来，一项研究成功克隆并表达了3株本土利什曼原虫（KS-6、SC6、JIASHI-1）的K26基因，制备重组抗原用于VL诊断，采用美国InBios公司rK39试纸条进行平行检测，比较3种抗原检测的灵敏度；ELISA检测结果显示，基于KS-6、SC6、JIASHI-1虫株表达的rK26抗原灵敏度分别为90.0％、92.7％、90.9％，rK39试纸条的灵敏度为93.6％，差异无统计学意义，所有检测方法的特异度均为100％［36］。但由于需要专业技术人员、精密设备和电力，ELISA在流行地区不用于VL的诊断。（三）分子生物学检测 1.PCR技术：在HIV-VL合并感染的诊断中，基于PCR的分子检测技术是一种有效的检测手段［37］。一项研究针对利什曼原虫小亚基核糖体RNA基因作为靶基因进行PCR检测，结果显示外周血灵敏度达98.5％，骨髓穿刺灵敏度为95.7％，其诊断效能显著优于传统方法（培养为76.2％，血清学为85.5％，镜检为90.2％）［38］。 2.qPCR：通过检测高拷贝数的动基体DNA（约10000个/虫）实现高灵敏度诊断，对口腔液样本灵敏度达100％［39］，广泛用于无症状感染的随访监测［40］。 3.LAMP：在苏丹等VL流行区，使用外周血LAMP检测的灵敏度为97.6％～100％，特异度达99.0％，效果优于DAT检测，可替代侵入性穿刺作为病原学确诊手段，适用于血清学初筛呈阴性但临床仍高度疑似VL的患者。此外，由于患者治愈后血清学抗体仍会长期存在，无法用以评估疗效或监测复发。而LAMP通过检测病原体DNA，仅在体内存在活寄生虫时才会显示阳性结果，所以成为监测治疗是否成功及疾病是否复发的理想工具［41］。 4.mNGS：在诊断VL时，mNGS能有效降低误诊与漏诊的风险。在中国西北地区的病例中，通过mNGS检测血液中利什曼原虫特异性序列，成功实现快速确诊，随后经rK39试纸条检测确认并成功治疗，凸显了mNGS技术在非流行区疑难病例诊断中的重要价值［42］。然而，鉴于其实验流程复杂、成本较高且报告解读要求高，其成本效益比低，因此，该技术当前主要用于复杂病例的鉴别诊断、流行病学调查和科研探索［43］。临床实践中，VL的诊断通常采取基于临床表现的联合诊断策略。常用方法包括快速免疫层析试纸（如rK39）、骨髓涂片镜检及分子检测（如qPCR）。“rK39检测＋骨髓涂片镜检”或“rK39检测＋qPCR”是最常采用的组合方案。对于免疫功能抑制患者等特殊人群，为提升诊断的灵敏性与准确性，推荐在上述基础上联合应用分子检测（如qPCR）技术。五、治疗 VL病例的临床表现主要为发热、脾肿大和全血细胞减少（三联征）［44］，部分患者伴有腹泻、黄疸、皮疹或乏力等全身症状［45-46］。误诊情况较为普遍，常被误判为血液系统疾病、系统性红斑狼疮或普通感染［45，47］。因此，提高临床诊断的及时性和准确性仍是VL临床防治的主要环节。目前在VL治疗方面，我国大部分地区仍以葡萄糖酸锑钠（sodium stibogluconate，SSG）为首选药物，对于重症患者则常联合使用两性霉素B。东非地区推广使用SSG联合巴龙霉素（paromomycin）方案［48］，南亚及拉美地区采用单剂量脂质体两性霉素B方案［49］，而米替福新（miltefosine）作为首个新型口服抗利什曼原虫药物也得到了广泛的临床应用［50］。近年来，一项在东非开展的多中心、Ⅲ期随机对照试验比较了巴龙霉素＋米替福新14d疗程与SSG＋巴龙霉素17d标准疗程的疗效，结果显示两组患者在6个月时的治愈率分别为91.2％和91.8％，疗效相当；但巴龙霉素＋米替福新联合治疗方案大幅减少了注射次数，显著提高患者依从性［51］。此外，新型候选药物LXE408正在埃塞俄比亚和印度进行Ⅱ期临床试验，未来有望作为一种安全、简便的全口服治疗方案［52］。疫苗研发被视为控制VL的关键策略，目前正沿三代技术路线不断推进。第一代全虫疫苗（如自灭活硕大利什曼原虫联合卡介苗）虽然在动物模型中显示部分保护，但在关键的人体Ⅲ期临床试验中没有提供足够的保护效果［53］，未能实现转化应用。第二代重组疫苗取得了实质性进展，其中重组蛋白疫苗Leish-Tec®作为目前唯一的商业化疫苗已被巴西批准用于犬类防控，显著降低感染率，但在人用适配方面仍存在限制［54］；而成簇规律间隔短回文重复序列（cluste redregularly interspaced short palindromic repeats，CRISPR）技术构建的减毒活疫苗如LmCen-/-和LmexCen-/-在仓鼠模型中对寄生虫负荷量均产生了很好的控制作用［55-56］，使其成为极具潜力进入人体临床试验评估的候选疫苗。近年来，第三代核酸疫苗快速发展，其中腺病毒载体疫苗ChAd63-KH已进入Ⅱ期临床试验，成为用于治疗VL的候选治疗性疫苗［57］。然而，疫苗研发仍面临重大挑战，除兽用疫苗Leish-Tec®外，尚无疫苗获批用于人类，ChAd63-KH等候选疫苗仍需通过Ⅲ期临床验证以实现真正转化应用。最危险的预后群体主要为年龄小、基础疾病多和营养差的人员［58］，多数患者经治疗后好转或治愈，而延误诊断和非规范治疗仍是死亡的重要因素［47］，因此建立高效的识别与规范的治疗体系至关重要。六、总结与展望面对日益加重的VL疾病与社会负担，本研究系统梳理了其三大流行类型（人源型、犬源型、野生动物源型）、以免疫逃逸为核心的致病机制，以及各类诊断技术（病原学、血清学、分子生物学）的优势与局限。治疗进展与临床转归揭示了临床实践中存在显著延误诊断现象，其核心问题在于临床医务人员的识别与诊断能力不足。因此亟需在高风险地区实施以重点人群筛查和病犬检测为核心的主动监测；推广具有高灵敏性与高特异性的诊断技术；并重点加强临床诊疗能力建设。上述策略为VL的精准防控提供了关键科学依据。利益冲突：所有作者声明不存在利益冲突志谢：文中图片均使用MedPeer（medpeer.cn）绘制作者贡献声明：贾玉琦：文献检索与筛选、论文撰写；冯旭飞：论文审阅与修改；白雪兵、李雁笛、姚添、张沛刚、王素萍、陈靖、冯永亮：论文审阅参考文献（略）（收稿日期：2025-07-15）（本文编辑：蒋蔚娜）免责声明:此文是我的读书记录,内容只是参考｡ (文章来源:《中华传染病杂》2025 年9月第43 卷第9 期)

2025-10-15

·生物制品圈

抗基孔肯雅病毒药物研究现状与未来方向

中文摘要基孔肯雅病毒（chikungunya virus，CHIKV）是由伊蚊传播的甲病毒。CHIKV感染可导致基孔肯雅热，近年来在全球范围内多次暴发，引发严重的公共卫生问题，目前尚无特异性抗病毒药物获批上市，临床治疗仍以对症和支持治疗为主。随着CHIKV传播范围的扩大和疾病负担的加重，开发有效的抗病毒药物成为迫切需求。此文综述了CHIKV的流行情况、基因组结构和功能以及近年来抗CHIKV药物，包括直接抗病毒药物、宿主靶向药物等的研究进展。此文还探讨了药物开发过程中面临的挑战，如发生耐药突变、药物安全性及临床转化等问题，并展望了未来研究方向，包括多靶点药物设计、联合用药策略以及计算机辅助药物设计与人工智能等。通过系统梳理现有研究成果，为抗CHIKV药物的进一步研发提供参考和启示。正文基孔肯雅病毒（chikungunya virus， CHIKV）属于披膜病毒科甲病毒属，是单股正链RNA病毒，主要通过伊蚊传播，人类感染后可导致基孔肯雅热（chikungunya fever， CHIKF）。CHIKF临床分为急性期与慢性期：急性期持续3~10 d，表现为突发高热（>39 ℃）、斑丘疹、严重关节痛（累及腕关节、踝关节等），伴淋巴细胞减少和血小板减少；慢性期则表现为持续性关节炎样症状，可持续数月至数年，甚至导致骨质破坏和功能障碍。尽管其致死率较低，但大部分患者的生活质量受到严重影响，并对家庭和社会带来沉重的经济负担。据统计，目前其已在全球造成超500亿美元潜在经济损失，波及119个国家和地区。2024年7月，WHO将CHIKV列为优先关注的高风险病原体之一。目前尚无CHIKV特异性治疗药物获批上市，临床上仍以对症和支持治疗为主。尽管目前已有2款疫苗获美国FDA批准用于高危人群，但其安全性还需进一步评估，且在我国仍未上市。研发安全有效的特异性抗CHIKV药物是当前的研究热点，也是迫切需要。本文重点介绍抗CHIKV药物的研发策略与候选药物，并总结药物研发面临的挑战，旨在为抗CHIKV药物的进一步研发提供参考和启示。 1 CHIKV概述 1.1 流行病学 CHIKV于1952年在非洲坦桑尼亚被首次报道，根据系统发育分析，CHIKV可分为3个基因型，分别为西非型、亚洲型、东中南非型。其中，西非型主要在西非国家通过森林循环小规模流行，而东中南非型则通过城市循环中的白纹伊蚊和埃及伊蚊感染人类，反复传播到新的地区，并在亚洲进化为独立的亚洲型。值得注意的是，2004年底东中南非型CHIKV包膜糖蛋白（envelope glycoprotein，E）1上的第226位氨基酸由丙氨酸突变为缬氨酸，使其在白纹伊蚊上的适应性增加近百倍，导致其传播范围大幅增加，成为了独立的印度洋分支亚型，并在肯尼亚暴发历史上最大的1次流行，从起源地非洲逐步扩大到印度洋、印度、东南亚和欧洲，导致了600多万人感染。目前，该病毒已在全球119个国家和地区形成传播风险，覆盖人口达28亿，其中东南亚、非洲及美洲地区负担最重，年均感染约3 530万例（95%置信区间：2 090万~5 650万），导致1 770万有症状病例、84.8万例慢性关节痛及3 700例死亡。我国自2008年以来已有多个省市出现CHIKF输入性病例，并于2010年开始发生本土流行。由于我国人群普遍易感，免疫屏障不足，因此CHIKV暴发流行风险持续存在。2025年7月18日，广东省佛山市暴发了1起由输入性病例引起的本地疫情。截至7月26日，广东省累计报告4 824例CHIKF本地病例。 1.2 病原生物学 CHIKV为单股正链RNA病毒，直径约70 nm，基因组全长约11.8 kb，其中包含5′端的7-甲基鸟苷帽和3′端的多腺苷酸尾以及2个开放阅读框（open reading frame， ORF）和3个非编码区（图1）。其中5′端ORF编码4种必需的非结构蛋白（nonstructural protein，nsP）——nsP1、nsP2、nsP3、nsP4，共同构成病毒复制复合物（replicative complex，RC）。nsP1具有甲基转移酶（methyltransferase，MTase）和鸟苷酸转移酶活性，负责病毒RNA的5'端加帽，其C末端棕榈酰化锚定RC于细胞质膜，是病毒复制必需环节；nsP2作为多功能蛋白酶和解旋酶，在病毒复制中起核心作用；nsP3通过甲病毒独特结构域（alphavirus unique domain，AUD）募集宿主因子，抑制宿主抗病毒应答；nsP4则作为RNA依赖的RNA聚合酶（RNA-dependent RNA polymerase，RdRp），催化合成子代基因组及亚基因组RNA。3′端ORF编码5种病毒结构蛋白，包括核衣壳蛋白（nucleocapsid protein，C）、E1和 E2以及2个较小的辅肽E3和6K。其中C自催化切割后包裹基因组RNA形成核衣壳；6K作为离子通道参与病毒组装与释放；E1、E2和E3以异源三聚体嵌入病毒包膜内，在病毒入侵靶细胞过程中发挥着关键作用。这些蛋白的协同作用实现了CHIKV基因组复制、免疫逃逸及子代病毒粒子组装释放的全生命周期。 1.3 生命周期 CHIKV感染细胞是高度有序的复杂过程，E2与宿主细胞表面受体结合后，募集网格蛋白向病毒结合处移动，从而诱导细胞以网格蛋白依赖途径内化病毒；随后，病毒在早期内体的低pH环境中发生构象变化，导致E1介导病毒包膜与内体膜融合，释放核衣壳至胞浆并解离出病毒RNA基因组，并在宿主细胞翻译合成非结构多蛋白前体P1234，该前体经病毒蛋白酶nsP2顺式切割产生P123与nsP4，二者形成早期RC，以正链基因组RNA为模板合成负链RNA。此后成熟的nsP1—4形成晚期RC，转而从负链RNA合成全长正链基因组RNA及亚基因组26S RNA。26S RNA编码结构多蛋白，最终通过出芽方式获得包膜并释放子代病毒颗粒，完成复制循环。 2 抗CHIKV药物研发策略与候选药物近年来，向CHIKV相关研究的投入不断增加，已有多种策略，包括基于细胞模型的高通量筛选（high throughput screening，HTS）、基于病毒蛋白晶体结构的合理药物设计、同源建模以及计算机辅助药物设计（computer aided drug design，CADD）应用于抗CHIKV药物研发。传统的基于细胞的HTS方法以病毒诱导的细胞病变效应减少为读数，来评估化合物的抗病毒活性，尤其适用于临床批准药物（如FDA批准的化合物库）的再利用研究。其核心优势在于显著缩短研发周期并降低开发成本。同时，该方法也存在简化生理环境和靶点模糊的局限性，其中最棘手的问题是筛选出的活性化合物在动物体内实验中经常难以复刻细胞模型上显著的抗病毒效果。值得关注的是，CADD的兴起极大地推动了CHIKV抑制剂的发现。该方法基于病毒蛋白结构进行虚拟筛选，并结合构效关系分析对先导化合物进行优化及衍生合成，继而在细胞水平验证其活性。CADD的应用受限于其靶向蛋白结构信息的匮乏。CHIKV复制酶（如nsP）中，目前仅nsP2的N端（RNA解旋酶）与C端（蛋白酶）结构域以及nsP3的N端大结构域得到解析。相比之下，结构蛋白（如E和C）的已知结构为靶向药物设计提供了更多机会。迄今为止，多数研究通过计算机模拟、体外实验或两者结合策略筛选CHIKV抑制剂，这些化合物在体内的疗效大多尚未明确。虽有少数化合物（如靶向nsP1的8-溴尿苷、靶向nsP2的MBZM-N-IBT、靶向nsP4的4′-氟尿苷等）在小鼠模型中展现出抗病毒活性，但靶向C的策略尚未建立体内有效性证据。总之，尽管研究者对CHIKV的药物研发已付出巨大努力，但绝大多数先导分子仍有待进行系统的体内评价及临床试验验证。目前，抗CHIKV候选药物主要分为直接作用的抗病毒药物（direct-acting antiviral agent，DAA）和宿主靶向治疗制剂（host-targeted agent，HTA）。 2.1 DAA 2.1.1　结构蛋白抑制剂　CHIKV包膜表面由80个三聚体刺突组成，每个刺突由E1和E2形成的异二聚体构成。E2主要负责介导病毒与宿主细胞表面受体的结合，其胞质尾部直接与C相互作用。病毒进入细胞后，作为Ⅱ类融合蛋白的E1介导病毒包膜与宿主细胞内体膜之间的融合。E3对于E1-E2异二聚体在反面高尔基网中的正确折叠与组装至关重要，且可以非共价方式与E1-E2异二聚体结合。当成熟病毒粒子释放至胞外中性pH环境时，E3发生解离，使E1和E2之间的酸敏感界面暴露在外，并在内体酸性pH环境的触发下，诱导E1介导的病毒膜融合过程。CHIKV的C包含3个关键结构域：高碱性区域、病毒基因组 RNA 结合区以及丝氨酸蛋白酶结构域。此外，C含有1个疏水结构域，该结构域直接与病毒E2的C端尾部相互作用，这一相互作用对于促进病毒粒子组装以及CHIKV通过宿主细胞质膜出芽至关重要。目前已发现多种药物针对结构蛋白发挥抗CHIKV作用。苏拉明是已获批用于治疗人类寄生虫感染的药物，该化合物被3项独立研究证实可在CHIKV进入细胞阶段发挥抑制作用。其作用机制可能涉及干扰CHIKV与宿主细胞的附着，阻碍病毒融合所必需的E1/E2异二聚体的构象变化等。研究者用C57BL/6小鼠模型进行动物研究，发现苏拉明可显著改善CHIKV不同临床分离株感染所诱导的足部肿胀、炎症反应及软骨损伤。阿比朵尔是已在俄罗斯、中国等国家获批用于治疗流感的广谱抗病毒药物。研究表明，其可抑制CHIKV复制周期的早期阶段。这一作用机制的发现源于筛选获得的阿比朵尔耐药CHIKV变异株在E2中的G82R突变。氯喹是古老的抗疟疾药物，同时表现出广泛的抗病毒活性，早在20世纪末就有多项关于氯喹抗CHIKV的研究。1984年发表的1项小规模队列研究评估了氯喹对CHIKF的疗效，观察到患者症状缓解，这为探索其用于治疗CHIKV提供了初步依据。遗憾的是，在2005—2006年留尼汪岛CHIKV流行期间进行的CuraChik试验与2006年印度CHIKV流行期间的1项临床试验中，氯喹的假定疗效被否定。总体而言，研究人员发现在细胞水平，在CHIKV感染后不同时间给予氯喹作用差异大：在感染早期阶段给药有效，其机制可能涉及干扰病毒-细胞表面相互作用并阻断内体酸化，从而抑制病毒内化过程；而在感染后期给药则可能产生不同或不利效应。姜黄素是姜黄提取物，常用于胃肠道疾病。有研究证实，其可通过抑制CHIKV在细胞表面的结合降低病毒颗粒感染性。绿茶中含量最高的儿茶素类化合物——表没食子儿茶素没食子酸酯在体外研究中展示了对CHIKV的抗病毒活性，其抗病毒活性靶向CHIKV进入细胞阶段，可能与干扰CHIKV中E的功能有关。已有研究证明，吡啶甲酸（picolinic acid，PCA）在CHIKV细胞感染模型中具有抗CHIKV活性。PCA通过与CHIKV C的疏水口袋结合，抑制C与E2胞质结构域之间的相互作用。由于其发挥作用所需的浓度较高，因此临床应用潜力受限。此外，研究人员将PCA研究结果与其他衣壳蛋白酶抑制剂（如二噁烷和哌嗪）的研究相结合，通过计算机设计预测发现了多个具有潜力的候选分子：3-氨基苯甲酸乙酯、P1，P4-二（腺苷-5'）四磷酸盐、乙酸依替巴肽和硫酸巴龙霉素。核酸适配体是具有不同构象的单链寡核苷酸，可与具有相对较高形状互补性的目标结合。因其具有可化学合成、低抗原性、以及计算科学筛选的可用性等良好的特性，而被认为是有前途的药物模式。Goto等利用最新的病毒样颗粒指数富集配体系统进化平台技术，以靶向CHIKV为模型，鉴定出抗CHIKV适配体Apt#1，并预测E2结构域A是其作用位点。 2.1.2　nsP抑制剂　nsP1是甲病毒复制的关键酶，兼具MTase和鸟苷酸转移酶活性，负责为病毒mRNA 5'端加帽。此帽结构对病毒mRNA翻译和抵抗宿主核酸外切酶降解至关重要。同时，nsP1通过中部两亲性螺旋（残基245—264）及C端棕榈酰化位点介导RC锚定于富含胆固醇的膜微域。其酶活性对病毒复制不可或缺，对其定点突变可致复制缺陷。近年来，nsP1因其独特的病毒mRNA加帽酶活性，成为开发高选择性抗CHIKV抑制剂的热门靶点。研究已鉴定出多个靶向nsP1的高效选择性抑制剂家族：MADTP系列（原型MADTP-314）：其耐药性由nsP1 N端单个突变P34S介导；CHVB系列（原型CHVB-032）：耐药性涉及nsP1 C端双突变S454G/W456R；FHA/FHNA：耐药性由nsP1突变G230R和K299E赋予。值得注意的是，MADTP与CHVB系列存在交叉耐药现象（P34S突变体对CHVB耐药，S454G/W456R突变体对MADTP耐药），提示二者可能靶向nsP1的相同功能域。此外，在间接影响病毒复制的宿主靶向药物也观察到nsP1相关的耐药性，如二氟甲基鸟氨酸通过耗竭宿主多胺发挥广谱抗病毒作用，CHIKV可通过nsP1双突变G230R/V326M获得耐药性。总之，大多数靶向nsP1的抑制剂需2个特定氨基酸突变组合才能产生显著耐药性，这一特性显著降低了治疗中产生耐药病毒株的风险，具有重要临床意义。由于对nsP1晶体结构的认知缺陷限制了对耐药突变分子机制和抑制剂作用模式的深入理解，因此对该领域的进一步研究将为开发基于nsP1的新型抗CHIKV药物奠定重要基础。 nsP2是在CHIKV感染中发挥多种功能的关键蛋白。其N端结构域具有核苷三磷酸酶、RNA解旋酶和RNA 5'三磷酸酶活性，分别参与病毒复制中双链RNA的解离和5'端帽结构形成前的去磷酸化。C端结构域包含蛋白酶活性和S-腺苷甲硫氨酸依赖性RNA MTase样结构域。蛋白酶负责切割病毒非结构多蛋白前体（nsp123/nsp1234），完成病毒复制过程。此外，甲病毒的nsP2可转运至宿主细胞核，通过诱导RNA聚合酶Ⅱ催化亚基RPB1的多泛素化，导致宿主转录关闭并抑制干扰素反应，其核定位及免疫抑制功能与C端S-腺苷甲硫氨酸MTase样结构域密切相关。鉴于其核心作用，nsP2（尤其是蛋白酶结构域）已成为抗病毒药物设计的重要靶标。经HTS发现的天然化合物ID1452-2可靶向CHIKV nsP2蛋白酶，在细胞水平呈现中等抗病毒活性（抑制中浓度为31 μmol/L），作用具有浓度依赖性。近期还发现FDA已批准的抗高血压药替米沙坦和抗菌药物新生霉素在低浓度下可有效抑制nsP2蛋白酶活性，该策略通过挖掘已上市药物新功能，加速抗CHIKV药物研发。综上，nsP2通过多酶活性协调病毒复制、逃避宿主免疫监视并劫持宿主因子，是极具潜力的抗病毒靶点，其抑制剂的开发需紧密结合计算预测与实验验证，以提升效力与特异性。 nsP3在CHIKV复制中的确切功能尚未被完全阐明。其结构包含3个关键域：N端大结构域、AUD以及C端高变结构域。N端大结构域高度保守，通过结合RNA和腺苷二磷酸（adenosine diphosphate，ADP）-核糖并发挥ADP-核糖水解酶活性调节病毒复制。此活性对病毒逃避宿主ADP核糖基化至关重要，其保守的ADP-核糖结合口袋是设计大结构域特异性抗病毒药物的理想靶点。CADD虽已从小片段化合物库中筛选出结合该口袋的小片段化合物，并经晶体浸泡和核磁共振验证，但因分子较小，无法在基于细胞模型的研究中用作抑制剂。当前研究者正利用计算机设计构建更大分子以提高抑制效能。近期有研究表明AUD可决定病毒宿主物种特异性，并在病毒基因组RNA转录和组装中起核心作用。AUD突变会损害CHIKV亚基因组RNA合成、RNA结合活性及nsP3亚细胞定位，进而抑制病毒复制，凸显其作为抗病毒靶点的价值。nsP3（包括AUD）还被报道通过与多种宿主因子（如鞘氨醇激酶2、热休克蛋白90、PI3K-Akt-哺乳动物雷帕霉素靶蛋白通路组分）相互作用促进病毒复制，可靶向这些互作过程进行抗病毒干预。C端高变结构域主要通过与宿主蛋白G3BP1相互作用，干扰应激颗粒形成，从而促进病毒复制。尽管nsP3各结构域在CHIKV复制周期中扮演关键角色，并与多种宿主因子存在重要互作，提供了丰富的潜在抗病毒靶点，但迄今针对nsP3开发抗病毒药物的研究仍非常有限。基于结构（尤其是大结构域ADP-核糖结合口袋和AUD）的合理药物设计是极具前景的研究方向。 nsP4是CHIKV最保守的病毒蛋白，其作为RdRp，负责基因组负链复制和26S 向导RNA转录。早期，它与P123形成RC合成负链模板；多蛋白加工后，与nsP1—4组成晚期RC合成基因组和向导RNA。nsP4还具有末端腺苷酸转移酶（terminal adenylyl transferase，TATase）活性，为基因组添加多腺苷酸尾，其对催化核心GDD基序中2个天冬氨酸对TATase活性至关重要。由于其独特的结构，RNA病毒的RdRp是药物开发的重要靶点，且大多数靶向nsP4的化合物均属于核苷类似物。如索非布韦作为尿苷类似物前药，经代谢活化形成三磷酸索磷布韦后，通过靶向CHIKV nsP4（分子对接预测）抑制病毒复制，在体外细胞模型及小鼠体内均可显著降低病毒载量并缓解关节炎症。法匹拉韦（T-705）为广谱核苷类似物，也可有效抑制CHIKV感染。在AG129小鼠模型中，法匹拉韦可显著降低脑部病毒载量并预防神经病变；在C57BL/6J小鼠的慢性感染期给予则无效，提示慢性感染中可能存在缺陷型病毒RNA。而利巴韦林则通过多机制抑制CHIKV，包括靶向RdRp。有研究表明，利巴韦林和多西环素联合使用可有效抑制 CHIKV 复制并减弱病毒在小鼠体内的感染性，仍需进一步的实验和临床研究来探讨它们在CHIKV临床干预中的潜在应用。综上所述，nsP4作为CHIKV最保守的病毒RdRp和TATase双功能酶，是广谱核苷类似物的有效靶点，同时其催化核心易受慢性感染中缺陷型病毒基因组干扰，且药物代谢活化效率与组织靶向性仍需优化以突破临床转化瓶颈。 2.2 HTA 鉴于病毒快速进化导致单一抗病毒疗法易引发耐药突变，开发靶向宿主因子的广谱抗病毒策略具有重要科学意义。HTA针对CHIKV治疗的优势在于其广谱抗病毒活性及低耐药风险，通过干预宿主细胞因子或免疫代谢通路阻断病毒感染与病理损伤，同时规避病毒高频突变导致的逃逸。HTA也存在一定局限性：靶向宿主关键蛋白（如基质重塑相关蛋白8受体）可能干扰生理功能（如组织重塑），诱发脱靶毒性；免疫代谢调控（如抑制细胞因子风暴）存在个体差异，易受宿主遗传背景影响；且多数策略仍限于体外验证，缺乏临床转化数据；此外，HTA对病毒直接杀伤效力较弱，需联合直接抗病毒药物以提升疗效。哈木薯碱及其类似物（高三尖杉酯碱、脱氧三尖杉酯碱）通过抑制真核翻译起始因子2α，阻断CHIKV ns翻译，进而抑制病毒RNA合成与结构蛋白表达，该机制亦见于其对抗EB病毒与流感病毒的广谱活性，且尚未见病毒耐药性报道，其临床应用仍需评估潜在脱靶效应及亚型特异性限制。Karlas等利用系统筛选策略进一步揭示了关键宿主靶点：采用全基因组干扰小RNA功能丧失筛选在HEK-293细胞中鉴定出156个促进CHIKV复制的前病毒因子及41个抗病毒宿主基因，据此通过药物重定位数据库锁定20种共6类靶向通路（液泡型H⁺-腺苷三磷酸酶、Cdc2样激酶、血管内皮生长因子4受体、钙调蛋白信号、脂肪酸合成、赖氨酸乙酰转移酶5）的小分子抑制剂。其中，脂肪酸合成抑制剂TOFA（靶向乙酰辅酶A羧化酶）与钙调蛋白抑制剂匹莫齐特联用，在小鼠模型中可显著协同抑制CHIKV复制并减轻关节肿胀。脂代谢通路中的胆固醇与鞘磷脂对于CHIKV感染尤其关键，用于维持CHIKV膜融合所需宿主膜微域结构，其合成酶如脂肪酸合酶和硬脂酰辅酶A去饱和酶-1的抑制剂（奥利司他、浅蓝菌素、CAY10566）可有效抑制CHIKV复制。此外，胆固醇转运抑制剂丙咪嗪及U18666A亦可阻断CHIKV的膜融合和复制过程。综上，宿主靶向治疗与多靶点药物联用为应对病毒耐药性提供了兼具广谱性与可持续性的抗病毒新范式。 3 讨论近年来，CHIKV的传播范围不断扩大，其相关的严重并发症也引起广泛关注，给人类生命健康造成严重影响，并带来巨大的经济损失。WHO于2024年将其列为需优先关注的高风险病原体之一。目前，仍无获批上市的抗病毒药物，仅可通过非甾体类抗炎药物来缓解基孔肯雅热患者的症状。虽然抗CHIKV药物研究的报道数不胜数，许多DAA和HTA在体外和动物模型中展现出良好的抗病毒活性，部分候选药物已进入早期临床试验阶段。然而，这些药物均未实现临床转化，药物开发仍面临多重挑战，包括病毒耐药性的潜在风险、急慢性阶段干预时机选择、临床转化瓶颈等。理论上，病毒复制周期中所有关键因素（包括病毒蛋白与必需宿主因子）均可作为抗病毒靶点。而靶向保守的病毒相关宿主因子虽也可产生广谱抗病毒活性，但亦可能伴随脱靶风险。采用不同作用机制的抗病毒药物联合治疗策略既可通过协同效应降低有效浓度从而减少不良反应，也有助于延缓耐药性的产生。抗病毒药物的最佳干预时机是感染急性期，此时用药可最大限度降低病毒载量，减少慢性病变风险。而针对患者组织的临床研究证实，关节组织中残留的病毒组分（RNA/蛋白质）才是引发免疫病理反应的主因。在慢性期开展抗病毒治疗，完整长度的病毒RNA已基本消失，针对病毒复制相关功能与宿主通路的效果有限。这强调需要全面把握急慢性疾病过程中病毒与宿主的相互作用机制，在急慢性阶段选择合适的干预时机和方法。临床转化瓶颈可能与动物模型与临床试验的局限性有关。现有CHIKV研究主要依赖小鼠模型，可分为致死性模型和关节炎模型。虽然致死性模型能提供更严格的抗病毒评估条件，但关节炎模型更具临床参考价值。二者在评估疗效时均有一定局限性，如关节炎模型无法完全模拟人类关节结构、力学负荷以及免疫应答，难以复现人类感染的自然病程；而致死性模型的局限性在于人类多器官感染和神经系统损伤的病例稀缺。截至目前，极少数进入临床试验的抗病毒药物（如氯喹等）均未发现有显著疗效。传统的药物设计耗时长、费用高，CADD和人工智能药物设计可通过最小化时间和经济成本来提高药物研发的效率，目前已成为现代药物发现的基石。这两种方法可以使用结构和配体方法预测药物分子活性起效结构以及与靶标的相互作用关系。在不断增加的数据可用性和持续的模型优化推动下，人工智能药物设计在过去10年中蓬勃发展。该项技术在蛋白质折叠、性质预测和分子生成方面展示了前所未有的优势，还可以促进目标识别、HTS和合成路线预测。尽管在新型冠状病毒的治疗方案中，通过该方法发现了一大类高效抗病毒药物分子，为治疗新型冠状病毒感染提供了新思路，但其在CHIKV抗病毒药物研究中的应用仍需进一步探索。从全球公共卫生角度来看，CHIKV流行区域分布广泛，单一国家的努力难以全面遏制疫情。建立跨国研发联盟、共享筛选平台与临床数据对加速安全有效药物问世至关重要。未来，需进一步深化病毒-宿主互作机制研究，同步优化动物模型临床相关性，推动天然产物资源利用与抑制剂急慢性双阶段疗效评价体系构建。这将为抗CHIKV靶点鉴定、高效分子开发、药物临床应用研究等提供重要助力。作者余晨阳宁欣航吴兵安朱香香戚中田钱汐晶海军军医大学海军医学系生物医学防护教研室，生物安全防御教育部重点实验室，上海市医学生物防护重点实验室，上海 200433 通信作者：钱汐晶， Email：437707827@qq.com 引用本文：余晨阳, 宁欣航, 吴兵安, 等. 抗基孔肯雅病毒药物研究现状与未来方向 [J]. 国际生物制品学杂志, 2025, 48(5): 361-369. DOI: 10.3760/cma.j.cn311962-20250801-00056 识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

疫苗临床研究申请上市上市批准

100 项与硫酸巴龙霉素相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	硫酸巴龙霉素	A07AA06	DB01421

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
阿米巴病	日本	Pfizer Japan, Inc.	2012-12-25
隐孢子虫病	-	-	1959-01-01
贾第虫病	-	-	1959-01-01

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
皮肤利什曼病	临床3期	美国	Appili Therapeutics, Inc.	2022-04-13
获得性免疫缺陷综合征	临床阶段不明	美国	Genetics Institute LLC	2001-08-31
常染色体显性视神经萎缩	临床前	中国	香港中文大学	2025-05-30
常染色体显性视神经萎缩	临床前	中国	汕头大学	2025-05-30
常染色体显性视神经萎缩	临床前	中国香港	香港理工大学	2025-05-30

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03399955 (Pubmed)	临床2期	黑热病后皮肤利什曼原虫 IFN-γ \| TNF \| IL-1β ... 更多	-	paromomycin plus miltefosine	網鹹蓋壓鏇獵齋遞製鹹(廠夢網衊鹽廠範築鏇顧) = 鬱願鏇願網製艱艱觸齋構築衊積廠簾鹹窪積製 (襯餘衊範鹹醖觸積膚觸 )	积极	2024-07-15
				liposomal amphotericin B plus miltefosine	網鹹蓋壓鏇獵齋遞製鹹(廠夢網衊鹽廠範築鏇顧) = 鑰膚廠糧繭餘顧製遞廠構築衊積廠簾鹹窪積製 (襯餘衊範鹹醖觸積膚觸 )
NCT03399955 (not available, Pubmed \| PLoS Negl Trop Dis)	临床2期	黑热病后皮肤利什曼原虫	110	Paromomycin/Miltefosine	齋鑰選獵餘艱觸糧蓋憲(壓願夢鹽構淵淵願築繭) = 夢鬱淵觸廠夢壓遞簾齋憲蓋鏇製選糧範繭壓衊 (獵窪餘夢壓襯遞糧獵積, 90.3 ~ 100)	积极	2023-11-21
				Liposomal Amphotericin B/Miltefosine	齋鑰選獵餘艱觸糧蓋憲(壓願夢鹽構淵淵願築繭) = 網遞積積築觸壓廠淵餘憲蓋鏇製選糧範繭壓衊 (獵窪餘夢壓襯遞糧獵積, 70.2 ~ 91.9)
NCT03129646 (Pubmed)	临床3期	内脏利什曼病	439	Paromomycin plus Miltefosine	顧願壓網壓選膚鏇夢淵(糧觸憲觸夢艱鹽構觸壓) = 觸鹽糧窪願鹽鹹願觸積艱製鑰膚糧艱遞窪鹹觸 (糧衊鑰遞衊淵壓繭範艱, -6.2 ~ 7.4)	积极	2022-09-27
				Sodium Stibogluconate plus Paromomycin	顧願壓網壓選膚鏇夢淵(糧觸憲觸夢艱鹽構觸壓) = 願襯遞鬱簾艱夢夢壓選艱製鑰膚糧艱遞窪鹹觸 (糧衊鑰遞衊淵壓繭範艱, -6.2 ~ 7.4)
NCT03759886 (Pubmed \| Int J Colorectal Dis)	N/A	-	120	Intervention group (oral paromomycin and metronidazole)	鏇醖網網遞顧廠糧齋鏇(範觸壓齋構蓋窪齋襯窪) = showed a tendency towards decreased frequencies in the intervention group 鬱範製製鹹鬱獵範願糧 (鬱鏇繭餘鬱簾廠艱廠憲 )	-	2021-04-25
				paromomycine (Control group (no intervention))
NCT03096457 (Pubmed \| Clin Infect Dis)	临床2/3期	皮肤利什曼病	80	15% Paromomycin-Aquaphilic	構艱鬱製衊襯製齋窪鑰(鬱淵窪膚蓋繭餘遞糧願) = 鬱醖衊襯遞觸遞鹽鏇糧夢憲獵選蓋繭鹽鹽遞範 (鹹壓獵範鑰鹹衊糧顧獵, 62.5 ~ 88)	-	2019-02-15
				Aquaphilic vehicle	構艱鬱製衊襯製齋窪鑰(鬱淵窪膚蓋繭餘遞糧願) = 願襯糧構築膚膚襯繭夢夢憲獵選蓋繭鹽鹽遞範 (鹹壓獵範鑰鹹衊糧顧獵, 3 ~ 30)
NCT01328457 (Pubmed \| PLoS Negl Trop Dis)	N/A	内脏利什曼病	120	Paromomycin Intramuscular Injection (PMIM)	觸鹹壓構艱壓鹽餘獵鹹(簾蓋構簾構鑰構簾憲窪) = Injection site pain was the most commonly reported adverse event 範觸繭壓艱窪願觸觸選 (齋構糧製選製淵淵築淵 ) 更多	积极	2015-01-01
NCT00255567 (Pubmed \| PLoS Negl Trop Dis)	临床2期	内脏利什曼病	42	Paromomycin 20 mg/kg/day for 21 days	齋壓壓築遞鏇觸壓壓齋(襯憲繭壓網築襯積淵鑰) = 獵衊艱窪鑰憲顧鹽廠築簾築糧鹽憲選衊廠築齋 (鑰淵築夢範製衊鬱淵選, 63.7% ~ 97.0%)	-	2010-10-26
				Paromomycin 15 mg/kg/day for 28 days	齋壓壓築遞鏇觸壓壓齋(襯憲繭壓網築襯積淵鑰) = 鏇糧窪齋餘築築糧顧製簾築糧鹽憲選衊廠築齋 (鑰淵築夢範製衊鬱淵選, 69.6% ~ 98.8%)
NCT00629031 (Pubmed \| Clin Infect Dis)	临床3期	内脏利什曼病	329	paromomycin (Group A)	襯廠衊鏇築蓋餘衊繭淵(衊鏇糧壓鑰餘獵顧窪醖) = Mild grade injection site pain was the most common adverse event 製鹽衊獵憲選鑰構齋簾 (廠艱膚鬱願簾齋醖餘簾 ) 更多	-	2009-09-15
				paromomycin (Group B)
NCT00216346 (Pubmed \| N Engl J Med)	临床3期	内脏利什曼病	667	Paromomycin	願遞構衊顧壓餘廠構鬱(衊顧淵選襯願窪壓網憲) = fevers 願顧壓顧鏇顧糧鑰鑰鑰 (鏇艱窪鏇醖鏇鏇鑰鑰簾 ) 更多	积极	2007-06-21
				Amphotericin B