头孢洛扎(Ceftolozane) - 药物靶点：PBPs_专利_临床

概要

基本信息

药物类型

小分子化药

别名

CXA-101、CXA-301、FR 264205

+ [1]

靶点

PBPs

作用方式

抑制剂

作用机制

PBPs抑制剂(细菌青霉素结合蛋白家族抑制剂)

治疗领域

感染呼吸系统疾病肿瘤+ [2]

在研适应症-

非在研适应症

复杂腹腔感染复杂的尿路感染粒细胞减少性发热+ [7]

原研机构

Merck Sharp & Dohme Corp.

在研机构-

非在研机构

Cubist Pharmaceuticals LLC

Calixa Therapeutics, Inc.

Merck Sharp & Dohme Corp.

权益机构

Cubist Pharmaceuticals LLC

Calixa Therapeutics, Inc.

Astellas Pharma, Inc.

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C23H30N12O8S2

InChIKeyJHFNIHVVXRKLEF-DCZLAGFPSA-N

CAS号689293-68-3

关联

7

项与头孢洛扎相关的临床试验

CTIS2024-516232-10-00

/ Not yet recruiting临床4期IIT

Defining Antibiotic Levels in Intensive care patients (DALI-2) protocol - A multi-national pharmacokinetic/pharmacodynamic cohort study to determine whether contemporary antibiotic dosing for critically ill patients achieves therapeutic exposures.

开始日期2025-12-01

申办/合作机构

Centre Hospitalier Universitaire de Nimes

NCT03963297

/ CompletedN/AIIT

Multicenter Evaluation of the Susceptibility of Enterobacteriaceae and Pseudomonas Aeruginosa to Ceftolozane/Tazobactam Combination

Ceftolozane/tazobactam is a new antibiotic with broad spectrum activity. This molecule is currently one of the most active beta lactams against Pseudomonas aeruginosa and its spectrum of activity also includes enterobacteriaceae producing a broad spectrum beta-lactamase (EBLSE). Ceftolozane/tazobactam is currently marketed for the treatment of complicated intra-abdominal infections and complicated urinary tract infections. These intra-abdominal and urinary infections are mainly caused by enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae) and more rarely by P. aeruginosa. Concerning enterobacteriaceae, French epidemiology reports a prevalence of BLSE of between 10 and 15% in E. coli and 10%-30% in K. pneumoniae.

开始日期2019-03-01

申办/合作机构

Fondation Hopital Saint-Joseph

EUCTR2018-000492-32-DE

/ Terminated临床4期IIT

Effects of antibiotics on micobiota, pulmonary immune response and incidence of ventilator-associated infections

开始日期2018-10-04

申办/合作机构

Charité - Universitätsmedizin Berlin

100 项与头孢洛扎相关的临床结果

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100 项与头孢洛扎相关的转化医学

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100 项与头孢洛扎相关的专利（医药）

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821

项与头孢洛扎相关的文献（医药）

2026-04-01·JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION

Longitudinal molecular epidemiology of ceftriaxone-resistant enterobacterales in intra-abdominal and urinary tract infections: A decade-long SMART surveillance study in Taiwan (2009–2019)

Article

作者: Lu, Po-Liang ; Lin, Shang-Yi ; Tang, Hung-Jen ; Liu, Chun-Eng ; Hsueh, Po-Ren ; Chen, Yao-Shen ; Tsao, Shih-Ming ; Wang, Fu-Der ; Ko, Wen-Chien ; Li, Yu-Hsun ; Chang, Ya-Ting ; Ho, Mao-Wang

BACKGROUND:

Third-generation cephalosporin-resistant Enterobacterales is a recognized global concern. This study investigated the molecular epidemiology of β-lactamase genes and antimicrobial susceptibility patterns among ceftriaxone-resistant Enterobacterales causing intra-abdominal and urinary tract infections in Taiwan between 2009 and 2019.

METHODS:

Data from the SMART surveillance program were analyzed, including Enterobacterales isolates with ceftriaxone minimum inhibitory concentrations ≥4 μg/mL. β-lactamase genes were detected using multiplex polymerase chain reaction assays.

RESULTS:

The overall ceftriaxone-resistant rate among Enterobacterales was 28.2 %, with a significant annual increase in ceftriaxone-resistant Klebsiella pneumoniae in both community- and hospital-acquired infections. Among the 2614 ceftriaxone-resistant isolates, the most common species were Escherichia coli (58.4 %), K. pneumoniae (16.3 %), and Enterobacter cloacae (9.9 %). Of all ceftriaxone-resistant isolates, 27.8 % carried only AmpC genes, 38.8 % carried only ESBL genes, and 16.2 % harbored both. High carriage rates of AmpC-encoding genes were observed in E. coli (38.9 %) and K. pneumoniae (48.9 %), with an overall prevalence of 44 %. The most common genotypes were bla_CMY (41.2 %), bla_DHA (31.8 %), and bla_ACT/bla_MIR (27 %). Ceftolozane/tazobactam showed poor susceptibility against ceftriaxone-resistant isolates carrying only AmpC (20.1 %) and most ceftriaxone-resistant Enterobacterales (<55 %), except E. coli. Ertapenem demonstrated low susceptibility to K. pneumoniae, E. cloacae (both approximately 50 %), and isolates harboring only AmpC genes (57.9 %).

CONCLUSIONS:

A high prevalence and diversity of AmpC genes were observed in E. coli and K. pneumoniae. The limited activity of ertapenem and ceftolozane/tazobactam suggests that the molecular mechanisms underlying ceftriaxone-resistant Enterobacterales in Taiwan are complex and likely involve factors beyond AmpC and ESBL carriage.

2026-03-01·INFECTIOUS DISEASE CLINICS OF NORTH AMERICA

Current Management Strategies of Difficult-to-Treat Resistant Pseudomonas aeruginosa Infections

Review

作者: Luque, Sonia ; Montero, Maria-Milagro ; Oliver, Antonio ; Paterson, David L ; Horcajada, Juan P

Difficult-to-treat resistant (DTR) Pseudomonas aeruginosa is an important cause of severe health care-associated infections and is associated with high morbidity and mortality. Its complex resistance mechanisms compromise the efficacy of traditional therapies and make treatment increasingly difficult. Although new active therapeutic options such as ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam and cefiderocol are currently available, lack of randomized control trials, drug access limitations, and emerging resistance have a negative impact on the management of these infections. This review discusses the mechanisms of resistance, molecular epidemiology, clinical management, and current and future therapeutic strategies for DTR P aeruginosa infections.

2026-03-01·INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS

Access to New Antibacterials in 10 Asian Countries: an Asian Network for Surveillance of Resistant Pathogens study

Article

作者: Bakthavatchalam, Yamuna Devi ; Veeraraghavan, Balaji ; Shimono, Nobuyuki ; Lee, Chia-Hui ; Song, Jae Hoon ; Putri, Nina Dwi ; Chan, Yuk-Ying ; Adnan, Syamhanin ; Tan, Sock Hoon ; Sia, Sonia ; Sulaiman, Helmi Bin ; Lee, Young Ho ; Perera, Jennifer ; Lye, David Chien ; Chiu, Cheng-Hsun ; Hashim, Rohaidah ; Huh, Kyungmin ; Kim, Yae Jean ; Thamlikitkul, Visanu ; Pratama, Evi ; Chung, Doo Ryeon ; Nasruddin, Azri Bin

BACKGROUND:

Although new molecular entity (NME) antibacterials active against multidrug-resistant organisms have been introduced, their availability remains limited even in developed countries. This study aimed to examine the current availability of NME antibacterial agents in Asia.

METHODS:

NME antibacterials approved by the US FDA from 2010 to 2024 were included. Approval status in ten Asian countries was collected as of June 2025. Population and economic status were sourced from the United Nations and World Bank databases. Investigators reported approval, withdrawal, and unit prices of study drugs as well as the type of healthcare systems using a standardised report form.

FINDINGS:

Among 22 NME antimicrobials included in this study, thirteen were approved in the surveyed countries. Beta-lactam/beta-lactamase inhibitors such as ceftazidime/avibactam and ceftolozane/tazobactam were the most approved class, each available in nine and eight countries, respectively. Agents active against carbapenem-resistant Acinetobacter spp. were available in three countries: cefiderocol (Japan, Singapore, Taiwan) and eravacycline (Singapore). The median number of available NME antibacterials per country was 3.5, ranging from one to six. For most NME antibacterials, a delay of three to five years existed between US FDA approval and approval in study countries. The number of available NME antibacterials showed no significant correlation with gross domestic product, relative drug price, or healthcare delivery system, except for approval lag.

INTERPRETATION:

Access to NME antibacterials in Asia remains markedly limited, with substantial approval delays. Considering the severity of antimicrobial resistance in the region, concerted efforts are warranted to improve access to crucial antibiotics in Asia.

32

项与头孢洛扎相关的新闻（医药）

2026-03-03

·北京医学感染与传染研究

国际抗微生物制剂杂志 67卷 1-3期

International Journal of Antimicrobial Agents Volume 67, Issue 1 国际抗微生物制剂杂志 67卷 1期 https://www.sciencedirect.com/journal/international-journal-of-antimicrobial-agents/vol/67/issue/1 International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page（国际抗菌化疗学会新闻与信息页） 1 International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page 国际抗菌化疗学会（ISAC）新闻与信息页 Article 107688 Antimicrobial Pharmacometrics（抗菌药物药代动力学） 2 Model-informed precision pyrazinamide dosing: The establishment of a population pharmacokinetic model repository for clinical decision support 基于模型的精准吡嗪酰胺剂量调整：建立用于临床决策支持的人群药代动力学模型库 Huan Zhang, Lu Han, Xiao-Qin Liu, Juan Wang, ... Zheng Jiao Article 107658 Global Landscape of Phage Therapy（噬菌体治疗的全球概况） 3 Nanomedicine for phage therapy: Encapsulation strategies for enhanced antimicrobial efficacy 噬菌体治疗的纳米医学：增强抗菌功效的封装策略 Alexis Dorta-Gorrín, Verónica Salgueiriño, Lorena García-Hevia Article 107660 4 Antibiotic-mediated prophage activation: Mechanisms, consequences, and therapeutic implications 抗生素介导的原噬菌体激活：机制、后果及治疗意义 Damir Gavric, Petar Knezevic Article 107655 5 Phage therapy for KPC-producing Klebsiella pneumoniae decolonization in high-risk patients: The KIDNAP Study Protocol – A prospective feasibility and proof of concept study in the Brazilian context 噬菌体治疗高风险患者中产KPC肺炎克雷伯菌的定植清除：KIDNAP研究方案——巴西背景下的一项前瞻性可行性及概念验证研究 Iris Najjar, Larissa Simão Gandolpho, Jôiciglecia Pereira dos Santos, Camila de Paula Siqueira, ... Ana C. Gales Article 107673 AI strategies to combat AMR（人工智能对抗抗菌药物耐药性的策略） 6 Development and validation of machine learning models to predict vancomycin- and teicoplanin-associated acute kidney injury: A retrospective, multicenter study 开发和验证机器学习模型用以预测万古霉素和替考拉宁相关的急性肾损伤：一项回顾性、多中心研究 Pin-Yi Lo, Fan-Ying Chan, Yi-En Ku, San-Yuan Wang, Hsiang-Yin Chen Article 107651 Reviews（综述） 7 A systematic review and meta-analysis of the global epidemiology of carbapenem-resistant Escherichia coli 碳青霉烯耐药大肠埃希菌全球流行病学的系统综述和荟萃分析 Mikaela M. Walker, Jason A. Roberts, Yixuan Li, Fekade B. Sime Article 107668 8 Molecular mechanisms of resistance and tolerance of Staphylococcus aureus to daptomycin 金黄色葡萄球菌对达托霉素耐药和耐受的分子机制 Candice Lim, Geoffrey W. Coombs, Shakeel Mowlaboccus Article 107678 Full Length Articles（长篇论著） 9 Antimicrobial peptide CATH-1 combats Streptococcus suis by targeting serine/threonine kinase 抗菌肽CATH-1通过靶向丝氨酸/苏氨酸激酶对抗猪链球菌 Yi Lu, Xiaoying Yu, Yandi Pan, Hang Yin, ... Rendong Fang Article 107656 10 The antiarrhythmic drugs dronedarone and amiodarone exhibit potent in vitro and in vivo activity against Clostridioides difficile 抗心律失常药物决奈达隆和胺碘酮对艰难梭菌表现出强效的体内外活性 Ahmed A. Abouelkhair, Nader S. Abutaleb, Mohamed N. Seleem Article 107649 11 Comparison of ceftazidime-avibactam with other appropriate antimicrobial therapy for the treatment of OXA-48- or KPC-producing Enterobacterales infections in Türkiye: A multi-centre retrospective matched-cohort study 头孢他啶-阿维巴坦与土耳其其他适当抗菌疗法治疗产OXA-48或KPC的肠杆菌目感染的比较：一项多中心回顾性匹配队列研究 Abdullah Tarık Aslan, Elif Seren Tanriverdi, Sibel Yıldız Kaya, Gozde Dalgan, ... Murat Akova Article 107650 12 An easy-to-use predictive score for identifying patients at risk of suboptimal linezolid exposure and candidates for therapeutic drug monitoring 一种易于使用的预测评分，用于识别存在利奈唑胺暴露不足风险及需进行治疗药物监测的患者 Daniel Fresán, Luisa Sorlí, Jaume Barceló-Vidal, Ana Rodrigo-Moreno, ... Sonia Luque Article 107661 13 Urinary exosome-derived microRNAs as biomarkers of tenofovir disoproxil fumarate (TDF)-induced renal toxicity in people with HIV-1 尿液外泌体衍生的微小RNA作为HIV-1感染者使用富马酸替诺福韦二吡呋酯（TDF）引起肾毒性的生物标志物 José L. Casado, Pilar Vizcarra, Francisco J. Hernández-Walias, José Manuel del Rey, ... Alejandro Vallejo Article 107654 14 Global genomic epidemiology of carbapenemase-producing Klebsiella pneumoniae, 1996–2023 1996-2023年产碳青霉烯酶肺炎克雷伯菌的全球基因组流行病学 Yuxia Shi, Dongxiao Ru, Minge Wang, Shengliang Cao, ... Jianbiao Lu Article 107657 15 Two Tail Protein-Derived Capsule Depolymerases From Phage vB_KpnS_GH-K1 are Effective Against Pneumonia Caused by K2 Serotype Klebsiella pneumoniae 来自噬菌体vB_KpnS_GH-K1的两种尾蛋白衍生的荚膜多糖解聚酶对K2血清型肺炎克雷伯菌引起的肺炎有效 Guiyang Ge, Hongbei Ge, Jianhui Xu, Bing Yue, ... Rui Du Article 107662 16 Discrepancy between WGS-based genotypic and phenotypic drug susceptibility testing of first and second-line drugs for Mycobacterium tuberculosis: Limited impact of unknown resistance mechanisms 结核分枝杆菌一线和二线药物基于全基因组测序的基因型与表型药物敏感性测试之间的差异：未知耐药机制的影响有限 Ruimin Hong, Peng Xu, Wenjie Lai, Chi Wu, ... Qian Gao Article 107666 17 Consumption and expenditure on fidaxomicin and oral vancomycin for Clostridioides difficile infection: A 12-year longitudinal study of 43 countries and regions 43个国家和地区12年艰难梭菌感染使用菲达霉素和口服万古霉素的消费和支出情况纵向研究 Yin Zhang, Xue Li, Angel Y.S. Wong, Vincent K.C. Yan, ... Wai K. Leung Article 107664 18 Genome-wide insight into the evolution and global transmission of tigecycline resistant tet(X4)-carrying Klebsiella species across reservoirs 全基因组视角下携带耐替加环素tet(X4)的克雷伯菌属在各储存库中的进化与全球传播 Yuye Wu, Yawen Yu, Xueqian He, Weifang Mao, ... Zhi Ruan Article 107665 19 Combined disk-based tests for phenotypic identification of KPC variants in Enterobacterales 基于联合药敏试验的肠杆菌目中KPC变异体的表型鉴定 Feng Yang, Li Ding, Siquan Shen, Chengkang Tang, ... Fupin Hu Article 107663 20 Impact of antimicrobial resistance measures and the emergence of COVID-19 on antimicrobial use throughout the Japanese population: A retrospective cohort study using a national claims database 抗菌药物耐药性措施的实施及新冠疫情的出现对日本全民抗菌药物使用的影响：一项使用国家索赔数据库的回顾性队列研究 Ryuji Koizumi, Shinya Tsuzuki, Yusuke Asai, Kensuke Aoyagi, Norio Ohmagari Article 107667 21 Ceftazidime-avibactam resistance among clinical isolates of Citrobacter freundii, Morganella morganii, Providencia spp. and Serratia marcescens across five continents: Data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme, 2016–2023 2016-2023年抗菌药物测试领导与监测（ATLAS）项目数据：五大洲弗氏柠檬酸杆菌、摩氏摩根菌、普罗维登斯菌属和产气肠杆菌临床分离株对头孢他啶-阿维巴坦的耐药性 Hao-En Jan, Jiun-Ling Wang, Nan-Yao Lee, Shun-Chung Hsueh, ... Po-Ren Hsueh Article 107669 22 Impact of DNA-stored mutations on virological response in virologically suppressed PWH in the switch to modern regimens DNA储存突变对病毒抑制的HIV感染者转换至现今治疗方案时病毒学反应的影响 Francesca Lombardi, Elio Gentilini Cacciola, Federica Carli, Francesco Saladini, ... Maria Mercedes Santoro Article 107670 23 NucS Thr74Ile confers mutator phenotype in a globally disseminated clinical Mycobacterium abscessus subsp. abscessus clone NucS Thr74Ile在全球传播的临床脓肿分枝杆菌脓肿亚种克隆中赋予突变表型 Juan Li, Junsheng Fan, Zhili Tan, Anqi Li, ... Haiqing Chu Article 107677 24 Adverse effects of posaconazole on adrenal steroid biosynthesis: An integrative approach using FAERS-based pharmacovigilance and systematic review with meta-analysis of randomised controlled trials 泊沙康唑对肾上腺类固醇生物合成的不良影响：基于FAERS的药物警戒和随机对照试验系统综述与荟萃分析的综合方法 Yuki Nakano, Kazumasa Kotake, Yuki Asai, Masayuki Murata, ... Hirotsugu Hasuwa Article 107676 25 SU3327: A multi-target compound targeting bacterial menaquinone and DNA SU3327：一种靶向细菌甲基萘醌和DNA的多靶点化合物 Shuge Wang, Ke Zhao, Ziqi Chen, Chengtao Sun, ... Dejun Liu Article 107679 26 blaKPC-2 amplification and a novel mrcA mutation drive Cefiderocol heteroresistance in ST11 CRKP blaKPC-2扩增和一种新型mrcA突变驱动ST11碳青霉烯耐药肺炎克雷伯菌对头孢地尔的异质性耐药 Yuxuan Liu, Hanxu Hong, QianBin Dai, Linping Fan, ... Yang Liu Article 107682 27 P1-like phage-plasmids drive blaCTX-M-27 transmission through lysogenic conversion and transposition P1样噬菌体质粒通过溶原性转换和转座驱动blaCTX-M-27传播 Zengfeng Zhang, Chunlei Shi Article 107686 28 Streptomyces taklimakanensis sp. nov. TRM43335 produces 3-indole carbaldehyde a promising inhibitor of carbapenem-resistant Acinetobacter baumannii: In vitro and in vivo evaluation 塔克拉玛干沙漠放线菌新种Streptomyces taklimakanensis sp. nov. TRM43335产生3-吲哚甲醛——一种有前景的碳青霉烯耐药鲍曼不动杆菌抑制剂：体内外评估 Yanchun Qin, Wen ting Zhou, Ling Wang, Shengqiang Yang, ... Hong Zeng Article 107685 Short Communications（短篇通讯） 29 Fluconazole exposure during mechanical circulatory support (MCS) device insertion 机械循环支持（MCS）装置植入期间的氟康唑暴露 Kelly A. Cairns, Kate Morton, Trisha N. Peel, Iain J. Abbott, ... Michael J. Dooley Article 107647 30 Evaluation of sulbactam-durlobactam disk diffusion and broth microdilution methods for Acinetobacter baumannii 评估磺苄西林-杜洛巴坦对鲍曼不动杆菌的纸片扩散法和肉汤微量稀释法 Xiaolan Hong, Xinying Wang, Xin Xiang, Siquan Shen, ... Yan Guo Article 107659 Letters to the Editor（读者来信） 31 Comment on “Comparison of ceftazidime-avibactam with other appropriate antimicrobial therapy for the treatment of OXA-48- or KPC-producing Enterobacterales infections in Turkiye: A multi-centre retrospective matched-cohort study” 对“土耳其头孢他啶-阿维巴坦与其他适当抗菌疗法治疗产OXA-48或KPC的肠杆菌目感染的比较：一项多中心回顾性匹配队列研究”的评论 S. Dhanya Dedeepya, Vaishali Goel, Nivedita Nikhil Desai Article 107671 32 Emergence of TMexCD-TOprJ-producing Vibrio furnissii in retail shellfish 零售贝类中出现产TMexCD-TOprJ的弗尼斯弧菌 Haotian Deng, Zhongpeng Cai, Kexin Li, Ludan Xiao, ... Shaowen Li Article 107680 International Journal of Antimicrobial Agents Volume 67, Issue 2 国际抗微生物制剂杂志 67卷 2期 https://www.sciencedirect.com/journal/international-journal-of-antimicrobial-agents/vol/67/issue/2 1 Title Page & Editorial Board 标题页与编委会 Article 107727 International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page（国际抗菌化疗学会（ISAC）新闻与信息页） 2 International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page 国际抗菌化疗学会（ISAC）新闻与信息页 Article 107719 Systematic Reviews and Meta-analyses（系统综述与荟萃分析） 3 Ceftazidime/avibactam and ceftolozane/tazobactam for severe paediatric infections: A systematic review, meta-analysis, and evidence map 头孢他啶/阿维巴坦与头孢洛扎/他唑巴坦治疗儿童重症感染：一项系统评价、荟萃分析及证据图谱研究 Paula Pimenta-de-Souza, Alice Ramos-Silva, Valcieny Sandes, Patrícia Portella, ... Elisangela Costa Lima Article 107710 Full Length Articles（长篇论著） 4 Downregulation of an NfsA-like nitroreductase causes metronidazole resistance in Gardnerella vaginalis NfsA样硝基还原酶下调可导致阴道加德纳菌对甲硝唑耐药 Ana Paunkov, Anna-Lena Mayr, Vera Oberbauer, Timo Schwebs, ... David Leitsch Article 107681 5 Machine–learning and gene–synergy networks reveal interpretable drivers of antibiotic resistance in Staphylococcus aureus 机器学习与基因协同网络揭示金黄色葡萄球菌抗生素耐药性的可解释驱动因素 Jie Xu, Yuan Li, Ying Wang, Fang Liu, ... Haiyan Yang Article 107690 6 Enhanced molecular surveillance for gonococcal resistance during doxycycline post-exposure prophylaxis implementation 在实施多西环素暴露后预防措施期间加强对淋球菌耐药的分子监测 Ziyuan Zhao, Leshan Xiu, Junping Peng Article 107689 7 Fosfomycin-based combinations against carbapenemase-producing Klebsiella pneumoniae bloodstream infections: Correlating in vitro synergy with clinical outcomes 以磷霉素为基础的联合用药治疗产碳青霉烯酶肺炎克雷伯菌血流感染：体外协同作用与临床预后的相关性 Melike Törüyenler Coşkunpınar, Güle Çınar, Duygu Öcal, İsmail Balık Article 107687 8 EnvZ mutation–driven downregulation of catecholate siderophore receptors and concurrent TonB complex repression confer cefiderocol resistance in a KPC-producing ST11-KL64 hypervirulent Klebsiella pneumoniae EnvZ突变驱动儿茶酚酸铁载体受体下调表达，同时抑制TonB复合体，使产KPC酶的ST11-KL64型高毒力肺炎克雷伯菌对头孢地尔产生耐药性 Danni Pu, Xianxia Zhuo, Rongrong Song, Chunhui Wang, ... Bin Cao Article 107693 9 Antibiotic class comparisons for the treatment of pyelonephritis and complicated urinary tract infections: A systematic review and meta-analysis 治疗肾盂肾炎和复杂性尿路感染的抗生素类别比较：一项系统综述和荟萃分析 Digbijay Kunwar, Itay Zahavi, Judit Olchowski, Hagar Dallasheh, Mical Paul Article 107696 10 Enhancing meropenem therapy in critical care: A retrospective study of PK/PD target attainment and therapeutic drug monitoring 强化重症监护病房中美罗培南的治疗：一项关于药代动力学/药效学目标达成情况及治疗药物监测的回顾性研究 Jingli Liao, Chao Li, Jingxian Liu, Wei Wu, ... Lixia Li Article 107697 11 Zinc deficiency reverses biofilm azole resistance in Candida albicans 锌缺乏可逆转白色念珠菌生物膜对唑类药物的耐药性 Yingzhe Wang, Shigan Ye, Yuan Deng, Yingting Huang, Xiaoliang Zhu Article 107695 12 Development of ceftazidime–avibactam resistance driven by conversion of blaKPC-2 to blaKPC-78 during treatment of ST463 carbapenem-resistant Pseudomonas aeruginosa infection 治疗ST463型碳青霉烯类耐药铜绿假单胞菌感染过程中，因blaKPC-2基因突变为blaKPC-78基因而引发的头孢他啶-阿维巴坦耐药性的产生 Haotian Xu, Tingjuan Zhang, Xueying Cui, Jingyi Guo, ... Xi Li Article 107703 13 ATP-binding cassette transporters mediate and regulate metronidazole resistance in Clostridioides difficile ATP结合盒转运蛋白介导并调控艰难梭菌对甲硝唑的耐药性 Teng Xu, Ying Zhou, Qingqing Xu, Li Wang, ... Haihui Huang Article 107709 14 Regorafenib, a multitargeted kinase inhibitor, inhibits enterovirus 71 infection by suppressing the MAPK pathway 瑞戈非尼（Regorafenib）作为一种多靶点激酶抑制剂，可通过抑制丝裂原活化蛋白激酶（MAPK）通路来抑制肠道病毒71型感染 Xinyu Zhang, Yuanyuan Cao, Yu Liu, Shengqun Deng, ... Qi Tang Article 107711 Short Communications（短篇通讯） 15 Effect of ibuprofen on the pharmacokinetics of intravenous flucloxacillin in healthy adults 布洛芬对健康成年人静脉注射氟氯西林药代动力学的影响 Alison Boast, Amy Legg, James McCarthy, Jason A Roberts, ... Amanda Gwee Article 107684 16 Formation of a novel multiresistance plasmid co-carrying tigecycline, carbapenem, and other resistance genes by recombination during conjugative transfer in Klebsiella pneumoniae 肺炎克雷伯菌在接合转移过程中通过重组形成一种共携带替加环素、碳青霉烯类及其他耐药基因的新型多重耐药质粒 Runhao Yu, Zhong Chen, Stefan Schwarz, Hong Yao, ... Xiang-Dang Du Article 107683 17 Vancomycin clearance compared to creatinine clearance by timed urine collection in the intensive care unit 重症监护室中通过定时尿液收集法比较万古霉素清除率与肌酐清除率 Andrew Chantha Hean, Rinoj Mathew, Frank Chu, Linda Awdishu Article 107704 18 Risk of infective endocarditis in oncohaematological patients undergoing active treatment with Enterococcus faecalis bloodstream infection: A retrospective multicentre study 接受积极治疗的血液肿瘤患者合并屎肠球菌（Enterococcus faecalis）血流感染时发生感染性心内膜炎的风险：一项回顾性多中心研究 Miguel Ángel Consuegra Pérez, Sara Grillo, Alexander Rombauts, María Alba Rivera Martínez, ... Laura Escolà-Vergé Article 107706 Letters to the Editor（致编辑的信） 19 In reply to the letter to editor regarding “Comparison of ceftazidime-avibactam with other appropriate antimicrobial therapy for the treatment of OXA-48- or KPC-producing Enterobacterales infections in Turkiye: A multi-centre retrospective matched-cohort study” 针对就《土耳其头孢他啶-阿维巴坦与其他适宜抗菌疗法治疗产OXA-48或KPC肠杆菌科感染的对比：一项多中心回顾性匹配队列研究》一文致编辑的信的回复 Abdullah T. Aslan, Patrick N.A. Harris, David L. Paterson Article 107691 20 Aztreonam–avibactam pharmacokinetics during extracorporeal membrane oxygenation support: First insights from a case report 体外膜肺氧合支持期间氨曲南-阿维巴坦的药代动力学特征：首例病例报告的初步见解 Alba Pau-Parra, Sònia Luque, Laura Doménech, María Martínez-Pla, ... Jordi Riera Article 107692 21 Comments on ‘Acute kidney injury associated with colistin sulphate vs. polymyxin B sulphate therapy: A real-world, retrospective cohort study’ 对“硫酸黏菌素与硫酸多黏菌素B治疗相关急性肾损伤：一项真实世界回顾性队列研究”的评论 Genzhu Wang Article 107702 22 Superintegron of Vibrio paracholerae as a reservoir of antibiotic resistance genes 副霍乱弧菌（或拟霍乱弧菌）超级整合子作为抗生素耐药基因的储存库 Sergio Mascarenhas Morgado, Erica Lourenço da Fonseca, Ana Carolina Paulo Vicente Article 107708 23 Clinical outcomes of metronidazole dosing strategies in obese patients with Bacteroides bloodstream infections 肥胖患者脆弱拟杆菌（Bacteroides）血流感染时甲硝唑不同给药策略的临床疗效 Sunish Shah, Rachel V. Marini, Dayna McManus, Ryan K. Shields, ... Tyler Tate Article 107701 Corrigendum（勘误表） 24 Corrigendum to “Impact of antimicrobial resistance measures and the emergence of COVID-19 on antimicrobial use throughout the Japanese population: A retrospective cohort study using a national claims database” [International Journal of Antimicrobial Agents Volume 67(2026)107667] 对《抗菌药物耐药性评估及新冠疫情的爆发对日本全民抗菌药物使用情况的影响：一项基于国家医保理赔数据库的回顾性队列研究》[《国际抗微生物制剂杂志》第67卷（2026年）第107667篇]的勘误说明 Ryuji Koizumi, Shinya Tsuzuki, Yusuke Asai, Kensuke Aoyagi, Norio Ohmagari Article 107694 International Journal of Antimicrobial Agents Volume 67, Issue 3 国际抗微生物制剂杂志 67卷3期 https://www.sciencedirect.com/journal/international-journal-of-antimicrobial-agents/vol/67/issue/3 1 Title Page & Editorial Board 目录与编委会 Article 107753 International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page（国际抗菌化疗学会（ISAC）新闻与资讯页面） 2 International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page 国际抗菌化疗学会（ISAC）新闻与资讯页面 Article 107746 Hot Topic（热点） 3 Artificial intelligence and machine learning in antimicrobial discovery, resistance prediction, and precision therapy 人工智能与机器学习在抗菌药物发现、耐药性预测及精准治疗中的应用 Reema Singh, Yu-Wei Lin, Jinxin Zhao, Jian Li Article 107715 Reviews（综述） 4 Pharmacokinetics and pharmacodynamics of bacteriophage therapy: A scoping review 噬菌体治疗的药代动力学和药效学：一项范围综述 Andrew T Nguyen, Nicita Mehta, KaiLan Mackey, Thomas Cummiskey, ... Jason Young Article 107705 5 Effect of probiotic strain, duration, and dose on preventing ICU-acquired infection: A scoping review 益生菌菌株、疗程及剂量对预防重症监护病房（ICU）获得性感染的影响：一项范围综述 Aqdar Mufareh Al-Aklabi, Sara Muteb Alotaishan, Yasmin Youssuf Al-Gindan, Rabie Yousif Khattab Article 107714 Full Length Articles（完整论著） 6 Pharmacokinetics of ampicillin, sulbactam and combined ampicillin/sulbactam in subcutis, muscle and plasma: A microdialysis trial in healthy volunteers 氨苄西林、舒巴坦及氨苄西林/舒巴坦联合用药在皮下、肌肉和血浆中的药代动力学：一项健康志愿者微透析试验 Anselm Jorda, Lena Pracher, Marlene Prager, Felix Bergmann, ... Valentin al Jalali Article 107716 7 Beneficial effects of a compound probiotic in Helicobacter pylori-infected patients aged over 40 years: An open-label randomised clinical trial 复合益生菌对40岁以上幽门螺杆菌感染患者的有益作用：一项开放标签随机临床试验 Chenghai Yang, Jie Cheng, Meng Zhang, Bingyun Lu, ... Ye Chen Article 107712 8 Skin pharmacokinetics and pharmacodynamics in patients with post-kala-azar dermal leishmaniasis 内脏利什曼病（黑热病）后皮肤利什曼原虫病患者的皮肤药代动力学与药效学 Wan-Yu Chu, Om Prakash Singh, Shyam Sundar, Krishna Pandey, ... Thomas P. C Dorlo Article 107713 9 Amodiaquine hydrochloride facilitates mycobacterial clearance via triggering autophagy in macrophages 盐酸阿莫地喹通过触发巨噬细胞自噬促进分枝杆菌清除 Hongxuan Yan, Jinfeng Yuan, Shujuan Duan, Fuzhen Zhang, ... Mengqiu Gao Article 107720 Short Communications（短篇通讯） 10 Risk factors for bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii in ICU patients with any site colonisation: a prospective observational study 重症监护病房（ICU）患者任何部位定植碳青霉烯耐药鲍曼不动杆菌造成血流感染的危险因素：一项前瞻性观察研究 Giusy Tiseo, Valentina Galfo, Aurelio Lepore, Manuela Pogliaghi, ... Marco Falcone Article 107717 11 Resistance to sulbactam/durlobactam in carbapenem-resistant Acinetobacter baumannii in treatment-naive setting: in vitro data and genomic insights from Italian bloodstream isolates 初次用药背景下耐碳青霉烯鲍曼不动杆菌对舒巴坦/杜洛巴坦的耐药性：来自意大利血流感染分离株的体外数据及基因组见解 Gabriele Bianco, Gherard Batisti Biffignandi, Matteo Boattini, Sara Comini, ... Paolo Gaibani Article 107718 12 Real-world daptomycin use with a focus on muscle toxicity: A multicentric retrospective study 聚焦肌肉毒性的达托霉素实际使用情况：一项多中心回顾性研究 C. Airaud, E. Demay, V. Dias Meireles, D. Luque Paz, ... A. Bacle Article 107721

2026-03-02

·北京医学感染与传染研究

国际抗微生物制剂杂志 67卷 1-3期（2026年3月2日更新）

International Journal of Antimicrobial Agents Volume 67, Issue 1 国际抗微生物制剂杂志 67卷 1期 https://www.sciencedirect.com/journal/international-journal-of-antimicrobial-agents/vol/67/issue/1 International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page（国际抗菌化疗学会新闻与信息页） 1 International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page 国际抗菌化疗学会（ISAC）新闻与信息页 Article 107688 Antimicrobial Pharmacometrics（抗菌药物药代动力学） 2 Model-informed precision pyrazinamide dosing: The establishment of a population pharmacokinetic model repository for clinical decision support 基于模型的精准吡嗪酰胺剂量调整：建立用于临床决策支持的人群药代动力学模型库 Huan Zhang, Lu Han, Xiao-Qin Liu, Juan Wang, ... Zheng Jiao Article 107658 Global Landscape of Phage Therapy（噬菌体治疗的全球概况） 3 Nanomedicine for phage therapy: Encapsulation strategies for enhanced antimicrobial efficacy 噬菌体治疗的纳米医学：增强抗菌功效的封装策略 Alexis Dorta-Gorrín, Verónica Salgueiriño, Lorena García-Hevia Article 107660 4 Antibiotic-mediated prophage activation: Mechanisms, consequences, and therapeutic implications 抗生素介导的原噬菌体激活：机制、后果及治疗意义 Damir Gavric, Petar Knezevic Article 107655 5 Phage therapy for KPC-producing Klebsiella pneumoniae decolonization in high-risk patients: The KIDNAP Study Protocol – A prospective feasibility and proof of concept study in the Brazilian context 噬菌体治疗高风险患者中产KPC肺炎克雷伯菌的定植清除：KIDNAP研究方案——巴西背景下的一项前瞻性可行性及概念验证研究 Iris Najjar, Larissa Simão Gandolpho, Jôiciglecia Pereira dos Santos, Camila de Paula Siqueira, ... Ana C. Gales Article 107673 AI strategies to combat AMR（人工智能对抗抗菌药物耐药性的策略） 6 Development and validation of machine learning models to predict vancomycin- and teicoplanin-associated acute kidney injury: A retrospective, multicenter study 开发和验证机器学习模型用以预测万古霉素和替考拉宁相关的急性肾损伤：一项回顾性、多中心研究 Pin-Yi Lo, Fan-Ying Chan, Yi-En Ku, San-Yuan Wang, Hsiang-Yin Chen Article 107651 Reviews（综述） 7 A systematic review and meta-analysis of the global epidemiology of carbapenem-resistant Escherichia coli 碳青霉烯耐药大肠埃希菌全球流行病学的系统综述和荟萃分析 Mikaela M. Walker, Jason A. Roberts, Yixuan Li, Fekade B. Sime Article 107668 8 Molecular mechanisms of resistance and tolerance of Staphylococcus aureus to daptomycin 金黄色葡萄球菌对达托霉素耐药和耐受的分子机制 Candice Lim, Geoffrey W. Coombs, Shakeel Mowlaboccus Article 107678 Full Length Articles（长篇论著） 9 Antimicrobial peptide CATH-1 combats Streptococcus suis by targeting serine/threonine kinase 抗菌肽CATH-1通过靶向丝氨酸/苏氨酸激酶对抗猪链球菌 Yi Lu, Xiaoying Yu, Yandi Pan, Hang Yin, ... Rendong Fang Article 107656 10 The antiarrhythmic drugs dronedarone and amiodarone exhibit potent in vitro and in vivo activity against Clostridioides difficile 抗心律失常药物决奈达隆和胺碘酮对艰难梭菌表现出强效的体内外活性 Ahmed A. Abouelkhair, Nader S. Abutaleb, Mohamed N. Seleem Article 107649 11 Comparison of ceftazidime-avibactam with other appropriate antimicrobial therapy for the treatment of OXA-48- or KPC-producing Enterobacterales infections in Türkiye: A multi-centre retrospective matched-cohort study 头孢他啶-阿维巴坦与土耳其其他适当抗菌疗法治疗产OXA-48或KPC的肠杆菌目感染的比较：一项多中心回顾性匹配队列研究 Abdullah Tarık Aslan, Elif Seren Tanriverdi, Sibel Yıldız Kaya, Gozde Dalgan, ... Murat Akova Article 107650 12 An easy-to-use predictive score for identifying patients at risk of suboptimal linezolid exposure and candidates for therapeutic drug monitoring 一种易于使用的预测评分，用于识别存在利奈唑胺暴露不足风险及需进行治疗药物监测的患者 Daniel Fresán, Luisa Sorlí, Jaume Barceló-Vidal, Ana Rodrigo-Moreno, ... Sonia Luque Article 107661 13 Urinary exosome-derived microRNAs as biomarkers of tenofovir disoproxil fumarate (TDF)-induced renal toxicity in people with HIV-1 尿液外泌体衍生的微小RNA作为HIV-1感染者使用富马酸替诺福韦二吡呋酯（TDF）引起肾毒性的生物标志物 José L. Casado, Pilar Vizcarra, Francisco J. Hernández-Walias, José Manuel del Rey, ... Alejandro Vallejo Article 107654 14 Global genomic epidemiology of carbapenemase-producing Klebsiella pneumoniae, 1996–2023 1996-2023年产碳青霉烯酶肺炎克雷伯菌的全球基因组流行病学 Yuxia Shi, Dongxiao Ru, Minge Wang, Shengliang Cao, ... Jianbiao Lu Article 107657 15 Two Tail Protein-Derived Capsule Depolymerases From Phage vB_KpnS_GH-K1 are Effective Against Pneumonia Caused by K2 Serotype Klebsiella pneumoniae 来自噬菌体vB_KpnS_GH-K1的两种尾蛋白衍生的荚膜多糖解聚酶对K2血清型肺炎克雷伯菌引起的肺炎有效 Guiyang Ge, Hongbei Ge, Jianhui Xu, Bing Yue, ... Rui Du Article 107662 16 Discrepancy between WGS-based genotypic and phenotypic drug susceptibility testing of first and second-line drugs for Mycobacterium tuberculosis: Limited impact of unknown resistance mechanisms 结核分枝杆菌一线和二线药物基于全基因组测序的基因型与表型药物敏感性测试之间的差异：未知耐药机制的影响有限 Ruimin Hong, Peng Xu, Wenjie Lai, Chi Wu, ... Qian Gao Article 107666 17 Consumption and expenditure on fidaxomicin and oral vancomycin for Clostridioides difficile infection: A 12-year longitudinal study of 43 countries and regions 43个国家和地区12年艰难梭菌感染使用菲达霉素和口服万古霉素的消费和支出情况纵向研究 Yin Zhang, Xue Li, Angel Y.S. Wong, Vincent K.C. Yan, ... Wai K. Leung Article 107664 18 Genome-wide insight into the evolution and global transmission of tigecycline resistant tet(X4)-carrying Klebsiella species across reservoirs 全基因组视角下携带耐替加环素tet(X4)的克雷伯菌属在各储存库中的进化与全球传播 Yuye Wu, Yawen Yu, Xueqian He, Weifang Mao, ... Zhi Ruan Article 107665 19 Combined disk-based tests for phenotypic identification of KPC variants in Enterobacterales 基于联合药敏试验的肠杆菌目中KPC变异体的表型鉴定 Feng Yang, Li Ding, Siquan Shen, Chengkang Tang, ... Fupin Hu Article 107663 20 Impact of antimicrobial resistance measures and the emergence of COVID-19 on antimicrobial use throughout the Japanese population: A retrospective cohort study using a national claims database 抗菌药物耐药性措施的实施及新冠疫情的出现对日本全民抗菌药物使用的影响：一项使用国家索赔数据库的回顾性队列研究 Ryuji Koizumi, Shinya Tsuzuki, Yusuke Asai, Kensuke Aoyagi, Norio Ohmagari Article 107667 21 Ceftazidime-avibactam resistance among clinical isolates of Citrobacter freundii, Morganella morganii, Providencia spp. and Serratia marcescens across five continents: Data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme, 2016–2023 2016-2023年抗菌药物测试领导与监测（ATLAS）项目数据：五大洲弗氏柠檬酸杆菌、摩氏摩根菌、普罗维登斯菌属和产气肠杆菌临床分离株对头孢他啶-阿维巴坦的耐药性 Hao-En Jan, Jiun-Ling Wang, Nan-Yao Lee, Shun-Chung Hsueh, ... Po-Ren Hsueh Article 107669 22 Impact of DNA-stored mutations on virological response in virologically suppressed PWH in the switch to modern regimens DNA储存突变对病毒抑制的HIV感染者转换至现今治疗方案时病毒学反应的影响 Francesca Lombardi, Elio Gentilini Cacciola, Federica Carli, Francesco Saladini, ... Maria Mercedes Santoro Article 107670 23 NucS Thr74Ile confers mutator phenotype in a globally disseminated clinical Mycobacterium abscessus subsp. abscessus clone NucS Thr74Ile在全球传播的临床脓肿分枝杆菌脓肿亚种克隆中赋予突变表型 Juan Li, Junsheng Fan, Zhili Tan, Anqi Li, ... Haiqing Chu Article 107677 24 Adverse effects of posaconazole on adrenal steroid biosynthesis: An integrative approach using FAERS-based pharmacovigilance and systematic review with meta-analysis of randomised controlled trials 泊沙康唑对肾上腺类固醇生物合成的不良影响：基于FAERS的药物警戒和随机对照试验系统综述与荟萃分析的综合方法 Yuki Nakano, Kazumasa Kotake, Yuki Asai, Masayuki Murata, ... Hirotsugu Hasuwa Article 107676 25 SU3327: A multi-target compound targeting bacterial menaquinone and DNA SU3327：一种靶向细菌甲基萘醌和DNA的多靶点化合物 Shuge Wang, Ke Zhao, Ziqi Chen, Chengtao Sun, ... Dejun Liu Article 107679 26 blaKPC-2 amplification and a novel mrcA mutation drive Cefiderocol heteroresistance in ST11 CRKP blaKPC-2扩增和一种新型mrcA突变驱动ST11碳青霉烯耐药肺炎克雷伯菌对头孢地尔的异质性耐药 Yuxuan Liu, Hanxu Hong, QianBin Dai, Linping Fan, ... Yang Liu Article 107682 27 P1-like phage-plasmids drive blaCTX-M-27 transmission through lysogenic conversion and transposition P1样噬菌体质粒通过溶原性转换和转座驱动blaCTX-M-27传播 Zengfeng Zhang, Chunlei Shi Article 107686 28 Streptomyces taklimakanensis sp. nov. TRM43335 produces 3-indole carbaldehyde a promising inhibitor of carbapenem-resistant Acinetobacter baumannii: In vitro and in vivo evaluation 塔克拉玛干沙漠放线菌新种Streptomyces taklimakanensis sp. nov. TRM43335产生3-吲哚甲醛——一种有前景的碳青霉烯耐药鲍曼不动杆菌抑制剂：体内外评估 Yanchun Qin, Wen ting Zhou, Ling Wang, Shengqiang Yang, ... Hong Zeng Article 107685 Short Communications（短篇通讯） 29 Fluconazole exposure during mechanical circulatory support (MCS) device insertion 机械循环支持（MCS）装置植入期间的氟康唑暴露 Kelly A. Cairns, Kate Morton, Trisha N. Peel, Iain J. Abbott, ... Michael J. Dooley Article 107647 30 Evaluation of sulbactam-durlobactam disk diffusion and broth microdilution methods for Acinetobacter baumannii 评估磺苄西林-杜洛巴坦对鲍曼不动杆菌的纸片扩散法和肉汤微量稀释法 Xiaolan Hong, Xinying Wang, Xin Xiang, Siquan Shen, ... Yan Guo Article 107659 Letters to the Editor（读者来信） 31 Comment on “Comparison of ceftazidime-avibactam with other appropriate antimicrobial therapy for the treatment of OXA-48- or KPC-producing Enterobacterales infections in Turkiye: A multi-centre retrospective matched-cohort study” 对“土耳其头孢他啶-阿维巴坦与其他适当抗菌疗法治疗产OXA-48或KPC的肠杆菌目感染的比较：一项多中心回顾性匹配队列研究”的评论 S. Dhanya Dedeepya, Vaishali Goel, Nivedita Nikhil Desai Article 107671 32 Emergence of TMexCD-TOprJ-producing Vibrio furnissii in retail shellfish 零售贝类中出现产TMexCD-TOprJ的弗尼斯弧菌 Haotian Deng, Zhongpeng Cai, Kexin Li, Ludan Xiao, ... Shaowen Li Article 107680 International Journal of Antimicrobial Agents Volume 67, Issue 2 国际抗微生物制剂杂志 67卷 2期 https://www.sciencedirect.com/journal/international-journal-of-antimicrobial-agents/vol/67/issue/2 1 Title Page & Editorial Board 标题页与编委会 Article 107727 International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page（国际抗菌化疗学会（ISAC）新闻与信息页） 2 International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page 国际抗菌化疗学会（ISAC）新闻与信息页 Article 107719 Systematic Reviews and Meta-analyses（系统综述与荟萃分析） 3 Ceftazidime/avibactam and ceftolozane/tazobactam for severe paediatric infections: A systematic review, meta-analysis, and evidence map 头孢他啶/阿维巴坦与头孢洛扎/他唑巴坦治疗儿童重症感染：一项系统评价、荟萃分析及证据图谱研究 Paula Pimenta-de-Souza, Alice Ramos-Silva, Valcieny Sandes, Patrícia Portella, ... Elisangela Costa Lima Article 107710 Full Length Articles（长篇论著） 4 Downregulation of an NfsA-like nitroreductase causes metronidazole resistance in Gardnerella vaginalis NfsA样硝基还原酶下调可导致阴道加德纳菌对甲硝唑耐药 Ana Paunkov, Anna-Lena Mayr, Vera Oberbauer, Timo Schwebs, ... David Leitsch Article 107681 5 Machine–learning and gene–synergy networks reveal interpretable drivers of antibiotic resistance in Staphylococcus aureus 机器学习与基因协同网络揭示金黄色葡萄球菌抗生素耐药性的可解释驱动因素 Jie Xu, Yuan Li, Ying Wang, Fang Liu, ... Haiyan Yang Article 107690 6 Enhanced molecular surveillance for gonococcal resistance during doxycycline post-exposure prophylaxis implementation 在实施多西环素暴露后预防措施期间加强对淋球菌耐药的分子监测 Ziyuan Zhao, Leshan Xiu, Junping Peng Article 107689 7 Fosfomycin-based combinations against carbapenemase-producing Klebsiella pneumoniae bloodstream infections: Correlating in vitro synergy with clinical outcomes 以磷霉素为基础的联合用药治疗产碳青霉烯酶肺炎克雷伯菌血流感染：体外协同作用与临床预后的相关性 Melike Törüyenler Coşkunpınar, Güle Çınar, Duygu Öcal, İsmail Balık Article 107687 8 EnvZ mutation–driven downregulation of catecholate siderophore receptors and concurrent TonB complex repression confer cefiderocol resistance in a KPC-producing ST11-KL64 hypervirulent Klebsiella pneumoniae EnvZ突变驱动儿茶酚酸铁载体受体下调表达，同时抑制TonB复合体，使产KPC酶的ST11-KL64型高毒力肺炎克雷伯菌对头孢地尔产生耐药性 Danni Pu, Xianxia Zhuo, Rongrong Song, Chunhui Wang, ... Bin Cao Article 107693 9 Antibiotic class comparisons for the treatment of pyelonephritis and complicated urinary tract infections: A systematic review and meta-analysis 治疗肾盂肾炎和复杂性尿路感染的抗生素类别比较：一项系统综述和荟萃分析 Digbijay Kunwar, Itay Zahavi, Judit Olchowski, Hagar Dallasheh, Mical Paul Article 107696 10 Enhancing meropenem therapy in critical care: A retrospective study of PK/PD target attainment and therapeutic drug monitoring 强化重症监护病房中美罗培南的治疗：一项关于药代动力学/药效学目标达成情况及治疗药物监测的回顾性研究 Jingli Liao, Chao Li, Jingxian Liu, Wei Wu, ... Lixia Li Article 107697 11 Zinc deficiency reverses biofilm azole resistance in Candida albicans 锌缺乏可逆转白色念珠菌生物膜对唑类药物的耐药性 Yingzhe Wang, Shigan Ye, Yuan Deng, Yingting Huang, Xiaoliang Zhu Article 107695 12 Development of ceftazidime–avibactam resistance driven by conversion of blaKPC-2 to blaKPC-78 during treatment of ST463 carbapenem-resistant Pseudomonas aeruginosa infection 治疗ST463型碳青霉烯类耐药铜绿假单胞菌感染过程中，因blaKPC-2基因突变为blaKPC-78基因而引发的头孢他啶-阿维巴坦耐药性的产生 Haotian Xu, Tingjuan Zhang, Xueying Cui, Jingyi Guo, ... Xi Li Article 107703 13 ATP-binding cassette transporters mediate and regulate metronidazole resistance in Clostridioides difficile ATP结合盒转运蛋白介导并调控艰难梭菌对甲硝唑的耐药性 Teng Xu, Ying Zhou, Qingqing Xu, Li Wang, ... Haihui Huang Article 107709 14 Regorafenib, a multitargeted kinase inhibitor, inhibits enterovirus 71 infection by suppressing the MAPK pathway 瑞戈非尼（Regorafenib）作为一种多靶点激酶抑制剂，可通过抑制丝裂原活化蛋白激酶（MAPK）通路来抑制肠道病毒71型感染 Xinyu Zhang, Yuanyuan Cao, Yu Liu, Shengqun Deng, ... Qi Tang Article 107711 Short Communications（短篇通讯） 15 Effect of ibuprofen on the pharmacokinetics of intravenous flucloxacillin in healthy adults 布洛芬对健康成年人静脉注射氟氯西林药代动力学的影响 Alison Boast, Amy Legg, James McCarthy, Jason A Roberts, ... Amanda Gwee Article 107684 16 Formation of a novel multiresistance plasmid co-carrying tigecycline, carbapenem, and other resistance genes by recombination during conjugative transfer in Klebsiella pneumoniae 肺炎克雷伯菌在接合转移过程中通过重组形成一种共携带替加环素、碳青霉烯类及其他耐药基因的新型多重耐药质粒 Runhao Yu, Zhong Chen, Stefan Schwarz, Hong Yao, ... Xiang-Dang Du Article 107683 17 Vancomycin clearance compared to creatinine clearance by timed urine collection in the intensive care unit 重症监护室中通过定时尿液收集法比较万古霉素清除率与肌酐清除率 Andrew Chantha Hean, Rinoj Mathew, Frank Chu, Linda Awdishu Article 107704 18 Risk of infective endocarditis in oncohaematological patients undergoing active treatment with Enterococcus faecalis bloodstream infection: A retrospective multicentre study 接受积极治疗的血液肿瘤患者合并屎肠球菌（Enterococcus faecalis）血流感染时发生感染性心内膜炎的风险：一项回顾性多中心研究 Miguel Ángel Consuegra Pérez, Sara Grillo, Alexander Rombauts, María Alba Rivera Martínez, ... Laura Escolà-Vergé Article 107706 Letters to the Editor（致编辑的信） 19 In reply to the letter to editor regarding “Comparison of ceftazidime-avibactam with other appropriate antimicrobial therapy for the treatment of OXA-48- or KPC-producing Enterobacterales infections in Turkiye: A multi-centre retrospective matched-cohort study” 针对就《土耳其头孢他啶-阿维巴坦与其他适宜抗菌疗法治疗产OXA-48或KPC肠杆菌科感染的对比：一项多中心回顾性匹配队列研究》一文致编辑的信的回复 Abdullah T. Aslan, Patrick N.A. Harris, David L. Paterson Article 107691 20 Aztreonam–avibactam pharmacokinetics during extracorporeal membrane oxygenation support: First insights from a case report 体外膜肺氧合支持期间氨曲南-阿维巴坦的药代动力学特征：首例病例报告的初步见解 Alba Pau-Parra, Sònia Luque, Laura Doménech, María Martínez-Pla, ... Jordi Riera Article 107692 21 Comments on ‘Acute kidney injury associated with colistin sulphate vs. polymyxin B sulphate therapy: A real-world, retrospective cohort study’ 对“硫酸黏菌素与硫酸多黏菌素B治疗相关急性肾损伤：一项真实世界回顾性队列研究”的评论 Genzhu Wang Article 107702 22 Superintegron of Vibrio paracholerae as a reservoir of antibiotic resistance genes 副霍乱弧菌（或拟霍乱弧菌）超级整合子作为抗生素耐药基因的储存库 Sergio Mascarenhas Morgado, Erica Lourenço da Fonseca, Ana Carolina Paulo Vicente Article 107708 23 Clinical outcomes of metronidazole dosing strategies in obese patients with Bacteroides bloodstream infections 肥胖患者脆弱拟杆菌（Bacteroides）血流感染时甲硝唑不同给药策略的临床疗效 Sunish Shah, Rachel V. Marini, Dayna McManus, Ryan K. Shields, ... Tyler Tate Article 107701 Corrigendum（勘误表） 24 Corrigendum to “Impact of antimicrobial resistance measures and the emergence of COVID-19 on antimicrobial use throughout the Japanese population: A retrospective cohort study using a national claims database” [International Journal of Antimicrobial Agents Volume 67(2026)107667] 对《抗菌药物耐药性评估及新冠疫情的爆发对日本全民抗菌药物使用情况的影响：一项基于国家医保理赔数据库的回顾性队列研究》[《国际抗微生物制剂杂志》第67卷（2026年）第107667篇]的勘误说明 Ryuji Koizumi, Shinya Tsuzuki, Yusuke Asai, Kensuke Aoyagi, Norio Ohmagari Article 107694 International Journal of Antimicrobial Agents Volume 67, Issue 3 国际抗微生物制剂杂志 67卷3期 https://www.sciencedirect.com/journal/international-journal-of-antimicrobial-agents/vol/67/issue/3 1 Title Page & Editorial Board 目录与编委会 Article 107753 International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page（国际抗菌化疗学会（ISAC）新闻与资讯页面） 2 International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page 国际抗菌化疗学会（ISAC）新闻与资讯页面 Article 107746 Hot Topic（热点） 3 Artificial intelligence and machine learning in antimicrobial discovery, resistance prediction, and precision therapy 人工智能与机器学习在抗菌药物发现、耐药性预测及精准治疗中的应用 Reema Singh, Yu-Wei Lin, Jinxin Zhao, Jian Li Article 107715 Reviews（综述） 4 Pharmacokinetics and pharmacodynamics of bacteriophage therapy: A scoping review 噬菌体治疗的药代动力学和药效学：一项范围综述 Andrew T Nguyen, Nicita Mehta, KaiLan Mackey, Thomas Cummiskey, ... Jason Young Article 107705 5 Effect of probiotic strain, duration, and dose on preventing ICU-acquired infection: A scoping review 益生菌菌株、疗程及剂量对预防重症监护病房（ICU）获得性感染的影响：一项范围综述 Aqdar Mufareh Al-Aklabi, Sara Muteb Alotaishan, Yasmin Youssuf Al-Gindan, Rabie Yousif Khattab Article 107714 Full Length Articles（完整论著） 6 Pharmacokinetics of ampicillin, sulbactam and combined ampicillin/sulbactam in subcutis, muscle and plasma: A microdialysis trial in healthy volunteers 氨苄西林、舒巴坦及氨苄西林/舒巴坦联合用药在皮下、肌肉和血浆中的药代动力学：一项健康志愿者微透析试验 Anselm Jorda, Lena Pracher, Marlene Prager, Felix Bergmann, ... Valentin al Jalali Article 107716 7 Beneficial effects of a compound probiotic in Helicobacter pylori-infected patients aged over 40 years: An open-label randomised clinical trial 复合益生菌对40岁以上幽门螺杆菌感染患者的有益作用：一项开放标签随机临床试验 Chenghai Yang, Jie Cheng, Meng Zhang, Bingyun Lu, ... Ye Chen Article 107712 8 Skin pharmacokinetics and pharmacodynamics in patients with post-kala-azar dermal leishmaniasis 内脏利什曼病（黑热病）后皮肤利什曼原虫病患者的皮肤药代动力学与药效学 Wan-Yu Chu, Om Prakash Singh, Shyam Sundar, Krishna Pandey, ... Thomas P. C Dorlo Article 107713 9 Amodiaquine hydrochloride facilitates mycobacterial clearance via triggering autophagy in macrophages 盐酸阿莫地喹通过触发巨噬细胞自噬促进分枝杆菌清除 Hongxuan Yan, Jinfeng Yuan, Shujuan Duan, Fuzhen Zhang, ... Mengqiu Gao Article 107720 Short Communications（短篇通讯） 10 Risk factors for bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii in ICU patients with any site colonisation: a prospective observational study 重症监护病房（ICU）患者任何部位定植碳青霉烯耐药鲍曼不动杆菌造成血流感染的危险因素：一项前瞻性观察研究 Giusy Tiseo, Valentina Galfo, Aurelio Lepore, Manuela Pogliaghi, ... Marco Falcone Article 107717 11 Resistance to sulbactam/durlobactam in carbapenem-resistant Acinetobacter baumannii in treatment-naive setting: in vitro data and genomic insights from Italian bloodstream isolates 初次用药背景下耐碳青霉烯鲍曼不动杆菌对舒巴坦/杜洛巴坦的耐药性：来自意大利血流感染分离株的体外数据及基因组见解 Gabriele Bianco, Gherard Batisti Biffignandi, Matteo Boattini, Sara Comini, ... Paolo Gaibani Article 107718 12 Real-world daptomycin use with a focus on muscle toxicity: A multicentric retrospective study 聚焦肌肉毒性的达托霉素实际使用情况：一项多中心回顾性研究 C. Airaud, E. Demay, V. Dias Meireles, D. Luque Paz, ... A. Bacle Article 107721

微生物疗法临床2期

2026-02-21

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氨基糖苷类抗生素的发展历程与临床研究进展

第一章氨基糖苷类抗生素的发现与发展历程1.1 首个氨基糖苷类药物 —— 链霉素的发现与历史溯源氨基糖苷类药物的研发纪元，始于链霉素的发现，其科学史争议与里程碑意义已成为现代医学史的重要研究课题。发现时间线的严谨界定关于链霉素的发现时间，史学界已形成明确共识：1943 年 10 月 19 日，阿尔伯特・沙茨（Albert Schatz）在实验室中成功从灰链霉菌（Streptomyces griseus）中分离出具有抗结核活性的链霉素单体，标志着该药物的实验室发现完成；1944 年 1 月，相关研究成果正式发表于《Proceedings of the Society for Experimental Biology and Medicine》，同年 11 月首次用于临床结核病患者治疗并获得成功，1945 年实现大规模工业化生产。史学界普遍以 1943 年作为链霉素的发现年份，将其定义为首个氨基糖苷类抗生素、首个用于临床的抗结核抗生素。发现者的科学史共识链霉素的荣誉归属是 20 世纪最著名的科学史争议之一，目前史学界已形成严谨定论：塞尔曼・瓦克斯曼（Selman Waksman）：罗格斯大学土壤微生物学教授，是系统性筛选土壤放线菌抗菌活性的项目总负责人，提出了 “抗生素” 与 “链霉菌属” 的核心概念，为研究提供了方向、平台与资源，1952 年因链霉素的发现荣获诺贝尔生理学或医学奖。阿尔伯特・沙茨（Albert Schatz）：瓦克斯曼实验室的博士研究生，是链霉素分离、纯化与活性鉴定的直接执行者，完成了核心实验工作。1950 年沙茨提起专利诉讼，1951 年罗格斯大学与其达成和解，正式确认其链霉素共同发现者的法律地位，并授予其专利使用费分成。现代科学史的共识为：链霉素的发现是瓦克斯曼建立的系统性筛选体系与沙茨的关键性实验工作共同的成果，其问世彻底终结了结核病作为 “不治之症” 的历史，开启了抗感染化疗的全新时代。1.2 天然氨基糖苷类的黄金发展期链霉素的成功激发了全球范围内从放线菌中筛选新型抗菌物质的热潮，1940-1960 年代迎来了天然氨基糖苷类药物研发的黄金时代，一系列核心药物相继问世，完成了从抗结核药物到广谱抗革兰氏阴性菌药物的跨越。新霉素（Neomycin） 1949 年由瓦克斯曼与 Lechevalier 团队从弗氏链霉菌中分离得到，是第二个上市的氨基糖苷类药物。其抗菌谱覆盖革兰氏阳性菌、革兰氏阴性菌与结核分枝杆菌，但因全身应用耳肾毒性显著，临床应用局限于局部用药（皮肤软组织、眼部感染）与肠道术前准备，至今仍是临床最常用的局部氨基糖苷类药物。卡那霉素（Kanamycin） 1957 年由日本抗生素之父梅泽滨夫团队从卡那霉素链霉菌中分离得到，为 4,6 - 二取代脱氧链霉胺类氨基糖苷的首个代表药物。其抗菌谱显著拓宽，对多数临床常见革兰氏阴性菌与耐链霉素结核分枝杆菌具有强效活性，1958 年上市后迅速成为 20 世纪 60 年代治疗严重革兰氏阴性菌感染的一线药物，也是抗结核治疗的核心二线药物。庆大霉素（Gentamicin） 1963 年，美国先灵葆雅公司与意大利 Lepetit 制药研究所合作，从棘孢小单孢菌（Micromonospora echinospora）与紫黑小单孢菌（Micromonospora purpurea）的发酵液中分离得到庆大霉素复合组分，1966 年正式获 FDA 批准上市，是氨基糖苷类发展史上的里程碑式药物。我国于 1965 年由中科院福建微生物研究所王岳教授团队，从福州湖泥中分离出该抗生素的国产生产菌株，1967 年完成结构鉴定，1969 年正式实现工业化投产并应用于临床（中文译名“庆大霉素”的含义即庆祝"九大”及工人阶级的伟大）。庆大霉素核心历史意义与临床价值包括：研发模式突破：是首个从链霉菌属以外的放线菌（小单孢菌属）中开发的临床用氨基糖苷类药物，打破了此前氨基糖苷类仅来源于链霉菌的研发局限，开启了从小单孢菌属筛选抗菌物质的全新方向；其命名遵循了放线菌来源抗生素的命名规范 —— 小单孢菌属产物后缀为「-micin」，区别于链霉菌属产物的「-mycin」，为后续同类药物的命名奠定了基础。抗菌活性飞跃：作为 4,6 - 二取代脱氧链霉胺类氨基糖苷，其抗菌谱较此前的链霉素、卡那霉素显著拓宽，对临床绝大多数需氧革兰氏阴性杆菌均具有强大杀菌活性，且是首个对铜绿假单胞菌具有强效抗菌作用的氨基糖苷类药物，填补了当时难治性非发酵菌感染的治疗空白。协同效应的确立：研究首次证实其与 β- 内酰胺类抗生素具有明确的协同杀菌效应 ——β- 内酰胺类破坏细菌细胞壁完整性，可显著促进庆大霉素的跨膜摄取，这一机制成为后续氨基糖苷类联合治疗的核心理论基础。临床应用的巅峰：上市后迅速取代卡那霉素，成为 1970-1990 年代全球范围内治疗严重需氧革兰氏阴性菌感染（医院获得性肺炎、血流感染、复杂性腹腔感染、肾盂肾炎等）的一线首选药物，也是免疫低下宿主粒细胞缺乏伴发热经验性治疗的核心组分。1970 年代，庆大霉素与青霉素 / 氨苄西林联合治疗肠球菌性感染性心内膜炎的方案被证实可实现协同杀菌，显著缩短疗程、降低死亡率，该方案至今仍是肠球菌心内膜炎标准治疗的重要组成部分。此外，庆大霉素因局部抗菌活性强、全身吸收极少，也被广泛用于局部感染治疗与外科术前准备，是临床应用场景最丰富的氨基糖苷类药物。妥布霉素（Tobramycin） 1967 年从黑暗链霉菌中分离得到，抗菌谱与庆大霉素相似，对铜绿假单胞菌的抗菌活性较庆大霉素强 2-4 倍，且耳肾毒性显著低于庆大霉素。上市后迅速成为囊性纤维化患者铜绿假单胞菌慢性肺部感染的首选治疗药物，也是医院获得性铜绿假单胞菌感染联合治疗的核心药物。这一时期的天然氨基糖苷类药物，与针对革兰氏阳性菌的青霉素类形成抗菌谱互补，共同构建了现代抗感染化疗的核心基础。1.3 应对耐药的半合成氨基糖苷类药物研发 20 世纪 70 年代起，随着质粒介导的氨基糖苷修饰酶（AMEs）全球传播，细菌对天然氨基糖苷类的耐药性快速上升，药物研发进入半合成结构修饰的新阶段，通过理性化学修饰引入空间位阻基团，规避耐药酶的修饰位点，开发出一系列抗耐药衍生物。阿米卡星（Amikacin） 1972 年上市，为卡那霉素 A 的半合成衍生物，在母核上引入 L-(-)-γ- 氨基 -α- 羟基丁酰基（AHBA）侧链，通过空间位阻效应规避了绝大多数临床常见 AMEs 的修饰，对 70% 以上耐庆大霉素、妥布霉素的革兰氏阴性菌仍保持抗菌活性。上市后迅速成为治疗多重耐药革兰氏阴性菌感染的核心药物，至今仍是全球范围内临床应用最广泛的二线氨基糖苷类药物。奈替米星（Netilmicin） 20 世纪 70 年代后期上市，为西索米星的半合成衍生物，可规避多种 AMEs 的修饰，抗菌谱与庆大霉素相似，耳肾毒性显著低于庆大霉素，尤其肾毒性风险有明确循证医学优势，临床多用于免疫低下患者的严重革兰氏阴性菌感染。异帕米星（Isepamicin） 1977 年研发成功，为卡那霉素 B 的半合成衍生物，在日本、欧洲及我国广泛应用。其结构修饰可规避绝大多数 AAC、APH、ANT 类耐药酶的修饰，抗耐药谱优于阿米卡星，且耳肾毒性更低，是治疗产酶耐药菌感染的重要选择。阿贝卡星（Arbekacin） 1990 年在日本上市，为地贝卡星的半合成衍生物，对甲氧西林耐药金黄色葡萄球菌（MRSA）与多重耐药革兰氏阴性菌均具有强效活性，是日本临床治疗多重耐药菌感染的核心药物。普拉佐米星（Plazomicin） 2018 年获 FDA 批准上市，为新一代半合成氨基糖苷类药物，以西索米星为母核进行结构修饰，可规避除 16S rRNA 甲基化酶（RMTs）外几乎所有临床常见 AMEs 的修饰，对产 AMEs 的多重耐药肠杆菌目细菌具有强效活性，是近 15 年来唯一获批上市的新型氨基糖苷类药物。半合成氨基糖苷类的研发，标志着抗菌药物从 “天然筛选” 向 “理性设计” 的关键跨越，为应对细菌耐药提供了持续的解决方案，巩固了氨基糖苷类在多重耐药菌感染治疗中的核心地位。第二章氨基糖苷类抗生素的作用机制与细菌耐药演化2.1 抗菌作用的分子机制氨基糖苷类为浓度依赖性快速杀菌剂，对需氧革兰氏阴性杆菌具有强效抗菌活性，对厌氧菌无抗菌作用，其分子作用机制具有高度特异性，核心过程分为三步：跨膜摄取过程：氨基糖苷类为多价阳离子化合物，首先通过静电作用与革兰氏阴性菌外膜脂多糖（LPS）上的阴离子位点结合，置换出稳定 LPS 结构的二价阳离子（Mg²⁺、Ca²⁺），破坏外膜完整性，完成跨外膜的快速摄取（能量依赖相 I，EDP-I）；随后通过严格依赖有氧呼吸电子传递链与质子动力势的主动转运过程，穿越细菌内膜进入胞质（能量依赖相 II，EDP-II）。该过程严格需氧，因此氨基糖苷类对厌氧菌无抗菌活性。核糖体靶点结合：进入胞质后，氨基糖苷类以高亲和力特异性结合细菌核糖体 30S 小亚基 16S rRNA 的解码区（A 位点），通过氢键、离子键形成稳定的药物 - 核糖体复合物。杀菌效应的核心机制：药物结合后产生两大致命协同效应：①翻译错读：诱导转运 RNA（tRNA）在 mRNA 密码子识别过程中发生错配，导致异常氨基酸插入新生肽链，合成无功能或毒性的异常蛋白；异常蛋白插入细菌细胞膜后，进一步破坏膜完整性，促进更多药物进入胞内，形成杀菌正反馈循环。②翻译过程阻滞：不可逆抑制核糖体翻译的延伸阶段，阻碍核糖体复合物的正常解离，阻断功能性蛋白的合成。两种效应协同作用，最终导致细菌快速死亡。2.2 细菌的核心耐药机制细菌针对氨基糖苷类的耐药机制可分为四大类，常协同出现导致高水平耐药，其中以氨基糖苷修饰酶与 16S rRNA 甲基化酶的临床意义最为重大。氨基糖苷修饰酶（Aminoglycoside-Modifying Enzymes, AMEs）介导的酶促失活：这是临床最常见、传播最广泛的耐药机制。细菌通过质粒、转座子、整合子等可移动遗传元件获得 AMEs 编码基因，表达的酶通过共价修饰药物分子的羟基或氨基，显著降低药物与核糖体靶点的亲和力，导致药物失效。临床常见的 AMEs 分为三大类：乙酰转移酶（AAC）：催化氨基的乙酰化，常见亚型包括 AAC (6')、AAC (3)，其中 AAC (6')-Ib 是全球革兰氏阴性菌中最流行的亚型，可修饰庆大霉素、妥布霉素等多种药物；磷酸转移酶（APH）：催化羟基的磷酸化，常见亚型为 APH (3')，可导致卡那霉素、新霉素高水平耐药；核苷转移酶（ANT）：催化羟基的腺苷酰化，常见亚型为 ANT (2'')，可介导庆大霉素、妥布霉素耐药。靶位点修饰介导的泛耐药：16S rRNA 甲基化酶（16S rRNA Methyltransferases, RMTs）：这是当前临床最严峻的耐药威胁。细菌表达的 RMTs 可对核糖体 16S rRNA 解码区的保守残基进行甲基化修饰，其中 G1405 位点的 m⁷G 甲基化可导致对所有临床常用 4,6 - 二取代脱氧链霉胺类氨基糖苷（庆大霉素、妥布霉素、阿米卡星、普拉佐米星等）的高水平交叉耐药（MIC>1024 mg/L）；A1408 位点的 m¹A 甲基化可介导对阿米卡星、阿贝卡星等药物的高水平耐药。编码 RMTs 的基因绝大多数位于可接合质粒上，极易在肠杆菌目、非发酵菌等院内致病菌间水平传播，常与碳青霉烯酶基因共存，是泛耐药革兰氏阴性菌感染治疗的核心难题。核糖体蛋白突变：编码核糖体 S12 蛋白的 rpsL 基因突变，可导致链霉素与靶点亲和力下降，是结核分枝杆菌对链霉素耐药的最主要机制，在其他临床致病菌中罕见。药物胞内浓度降低：外膜通透性下降：细菌外膜孔蛋白编码基因缺失或表达下调，可减少氨基糖苷类的跨外膜摄取，通常导致低至中度耐药，常与其他耐药机制协同放大耐药水平；主动外排泵过表达：细菌过表达能量依赖的多药外排泵（如肠杆菌目 AcrAB-TolC 系统、铜绿假单胞菌 MexXY-OprM 系统），可将胞内药物主动泵出，降低胞内药物浓度，常介导低水平交叉耐药，是多重耐药表型的重要组成部分。其他辅助耐药机制：包括药物隔离、细菌生物被膜形成、能量代谢通路突变导致药物主动摄取受阻等，多作为辅助机制协同放大耐药效应。2.3 克服耐药的核心策略针对上述耐药机制，目前已形成药物研发与临床应用相结合的多层次应对策略：结构修饰开发抗耐药衍生物：通过对氨基糖苷母核进行理性化学修饰，引入空间位阻基团，规避 AMEs 的修饰位点，是克服耐药的核心研发路径，代表药物包括阿米卡星、异帕米星、普拉佐米星等。氨基糖苷修饰酶抑制剂（AMEIs）研发：借鉴 β- 内酰胺类 /β- 内酰胺酶抑制剂复合制剂的成功模式，开发可特异性抑制 AMEs 活性的小分子化合物，与氨基糖苷类联用恢复其抗菌活性。研究中的抑制剂包括蛋白激酶抑制剂、双底物模拟物、抗菌肽等，但尚无产品获批进入临床常规应用。优化联合用药方案：经典方案为氨基糖苷类与 β- 内酰胺类联用，二者可通过破坏细胞壁与抑制蛋白合成实现协同杀菌，同时减少单药剂量、延缓耐药发生。对于多重耐药菌感染，也可根据药敏结果与多粘菌素、替加环素等药物联用，强化杀菌效应。基于 PK/PD 原理的给药方案优化：氨基糖苷类的杀菌疗效与峰浓度 / MIC 比值密切相关，而毒性与药物谷浓度、组织蓄积量正相关。基于此，临床已全面转向每日单次给药方案，多项大样本循证医学研究证实，该方案可显著提升杀菌疗效，同时使肾毒性发生率较传统每日多次给药降低 30% 以上，耳毒性风险相当或更低。同时，“治疗药物监测（TDM）”已成为氨基糖苷类临床应用的标准护理，通过监测峰浓度（目标 8-10×MIC）与谷浓度（目标 < 0.5mg/L），实现个体化给药，平衡疗效与安全性。第三章氨基糖苷类抗生素的临床应用演变与精准定位3.1 临床应用的历史变迁氨基糖苷类的临床应用历程，是一部从广谱一线用药到精准定位的演变史。20 世纪 60-80 年代，以庆大霉素、妥布霉素为代表的氨基糖苷类，凭借广谱强效的杀菌活性、明确的协同效应，成为治疗严重需氧革兰氏阴性菌感染的一线首选药物，同时在抗结核治疗、感染性心内膜炎联合治疗中占据核心地位。20 世纪 80 年代后期起，其临床一线应用范围逐渐收缩，核心驱动因素包括：① 第三代头孢菌素、碳青霉烯类、氟喹诺酮类等新型广谱抗生素相继上市，此类药物抗菌谱匹配度高，耳肾毒性显著更低，给药便捷，迅速替代氨基糖苷类成为常规感染的一线治疗药物；② 细菌耐药性持续上升，AMEs 与 RMTs 的全球传播，导致部分菌株对临床常用氨基糖苷类全面耐药；③ 对药物不可逆耳毒性的认知深化，以及医疗安全管理的规范化，促使临床更审慎地选择用药方案。3.2 毒性特征与现代化安全性管理氨基糖苷类的剂量限制性毒性主要为肾毒性与耳毒性，其发生机制与药物在组织内的蓄积密切相关。肾毒性：临床最常见，发生率约 10%-25%。药物通过 megalin 受体介导的内吞作用在肾脏近曲小管上皮细胞内蓄积，导致溶酶体破裂、线粒体损伤、细胞凋亡坏死，临床表现为非少尿型急性肾损伤，绝大多数患者停药后肾功能可逐渐恢复。耳毒性：包括前庭毒性与耳蜗毒性，总体发生率约 3%-15%。药物可通过血 - 迷路屏障进入内耳淋巴液，在耳蜗毛细胞与前庭毛细胞内蓄积，导致毛细胞不可逆凋亡坏死。耳蜗毒性表现为高频听力先受损，可进展为全频不可逆性耳聋；前庭毒性表现为眩晕、平衡失调、眼球震颤，部分患者可通过前庭代偿缓解症状。耳毒性具有明显的个体差异与遗传易感性，线粒体 12S rRNA A1555G、C1494T 突变携带者对氨基糖苷类耳毒性高度敏感，可出现 “一针致聋”，此类人群绝对禁用氨基糖苷类药物。当前临床已形成完善的氨基糖苷类安全性管理体系：① 严格患者筛选，避免用于已有肾功能不全、听力障碍、脱水、高龄患者及线粒体耳聋易感基因突变携带者，除非获益显著大于风险；② 全面推行每日单次给药方案，减少药物组织蓄积；③ 常规开展 TDM，个体化调整给药剂量与间隔，严格控制谷浓度；④ 用药期间密切监测肾功能、听力变化，及时发现并干预毒性反应。3.3 当前临床精准应用的核心场景尽管不再作为广谱一线用药，氨基糖苷类凭借其独特的杀菌机制、明确的协同效应、较低的诱导耐药风险，在现代抗感染治疗中仍具有不可替代的精准定位，核心应用场景包括：多重耐药革兰氏阴性菌感染的联合治疗：对于耐碳青霉烯类肠杆菌目细菌（CRE）、耐碳青霉烯类铜绿假单胞菌（CRPA）、耐碳青霉烯类鲍曼不动杆菌（CRAB）等多重耐药 / 泛耐药革兰氏阴性菌引起的严重感染，若体外药敏试验显示菌株对阿米卡星、普拉佐米星等药物敏感，氨基糖苷类可作为联合治疗方案的核心组分之一，与新型 β- 内酰胺 /β- 内酰胺酶抑制剂复合制剂、多粘菌素等药物联用，强化杀菌效应，降低治疗失败风险。国内外权威指南均明确指出，氨基糖苷类不推荐单药用于严重血流感染、肺炎等深部组织感染，仅可在药敏支持下用于非复杂性尿路感染的单药治疗。特定感染的协同治疗：感染性心内膜炎：庆大霉素与青霉素类、氨苄西林、万古霉素等药物联用，是治疗链球菌属、肠球菌属、葡萄球菌属所致感染性心内膜炎的经典方案，可实现协同杀菌，显著缩短疗程、降低复发率与死亡率。铜绿假单胞菌严重感染：妥布霉素、阿米卡星与抗假单胞菌 β- 内酰胺类联用，是治疗铜绿假单胞菌所致医院获得性肺炎、血流感染、囊性纤维化患者慢性肺部感染的首选方案之一，可显著提升细菌清除率。分枝杆菌感染治疗：(1)结核病：链霉素、阿米卡星、卡那霉素是 WHO 推荐的耐多药结核病（MDR-TB）、广泛耐药结核病（XDR-TB）联合治疗方案中的核心二线药物，用于对一线抗结核药物耐药或不耐受的患者。(2)非结核分枝杆菌感染：阿米卡星是治疗脓肿分枝杆菌、鸟分枝杆菌复合群（MAC）等非结核分枝杆菌所致肺部、皮肤软组织感染的关键药物。局部应用:新霉素、庆大霉素、妥布霉素等药物因局部抗菌活性强、全身吸收极少，广泛用于皮肤软组织感染、眼部感染、耳部感染的局部治疗，以及外科肠道术前准备、腹腔冲洗等局部用药场景。第四章 2020-2026 年临床研究进展与指南更新4.1 新一代氨基糖苷类的临床研究进展普拉佐米星是近 15 年来唯一获批上市的新型半合成氨基糖苷类药物，2020-2026 年间，多项临床研究进一步明确了其临床定位与应用价值： EPIC III 期临床研究：该多中心、随机、双盲、非劣效性研究纳入 1153 例复杂性尿路感染（cUTI）与急性肾盂肾炎患者，对比普拉佐米星每日 15mg/kg 单药治疗与美罗培南的疗效与安全性。结果显示，在微生物学改良意向治疗人群中，普拉佐米星组的复合临床治愈与微生物清除终点达标率为 81.7%，与美罗培南组（70.1%）相比达到非劣效性标准，且安全性良好，肾毒性发生率与对照组相当。该研究为普拉佐米星用于 cUTI 的单药治疗提供了高级别循证医学证据。 CARE III 期临床研究：该研究纳入 398 例由 CRE 引起的严重感染（包括医院获得性肺炎、血流感染、复杂性腹腔感染）患者，对比普拉佐米星联合甲硝唑与黏菌素联合甲硝唑的疗效与安全性。结果显示，普拉佐米星组的 28 天全因死亡率为 23.8%，与黏菌素组（27.5%）无统计学差异，未达到优效性终点；但普拉佐米星组的肾毒性发生率显著低于黏菌素组（14.5% vs 30.8%），安全性更具优势。该研究提示，对于 CRE 所致严重感染，普拉佐米星可作为黏菌素的低毒性替代方案，用于联合治疗的组分之一，但仍不推荐单药应用。 2020-2026 年间，多项真实世界研究进一步证实，对于产超广谱 β- 内酰胺酶（ESBLs）、产碳青霉烯酶的肠杆菌目细菌所致 cUTI，普拉佐米星单药治疗可获得较高的微生物清除率与临床治愈率，是多重耐药菌所致尿路感染的重要治疗选择。4.2 国际权威指南的更新与定位调整 2024-2025 年，美国感染病学会（IDSA）、欧洲临床微生物与感染病学会（ESCMID）相继更新了多重耐药革兰氏阴性菌感染治疗指南，对氨基糖苷类的临床定位进行了明确与细化，核心趋势包括：强调基于药敏结果的个体化精准应用：指南不再对氨基糖苷类进行笼统的推荐，而是明确要求仅在体外药敏试验证实菌株敏感的前提下，将其纳入治疗方案；需根据感染部位、患者肾功能状态、PK/PD 原理制定个体化给药方案，并常规开展 TDM。明确联合治疗中的定位：对于 CRE、CRPA、CRAB 所致严重感染，指南均将新型 β- 内酰胺 /β- 内酰胺酶抑制剂复合制剂（头孢他啶 / 阿维巴坦、头孢洛扎 / 他唑巴坦、美罗培南 / 法硼巴坦等）、头孢地尔等作为优先推荐的核心治疗药物；氨基糖苷类（阿米卡星、普拉佐米星，若药敏敏感）仅作为联合治疗的辅助组分，用于无法使用核心药物、存在高死亡风险的重症患者，或用于提升微生物清除率、降低耐药发生风险。限定单药治疗的适用场景：指南明确指出，氨基糖苷类仅可单药用于非复杂性 / 复杂性尿路感染（药敏敏感前提下），严禁单药用于血流感染、肺炎、中枢神经系统感染等深部组织严重感染。安全性管理的强化推荐：所有指南均将每日单次给药方案作为氨基糖苷类的首选给药方式，将 TDM 作为标准护理措施，明确了峰浓度与谷浓度的控制目标，并强调用药前需筛查线粒体耳聋易感基因突变，降低不可逆耳毒性风险。

临床研究微生物疗法寡核苷酸

100 项与头孢洛扎相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	头孢洛扎	J01DI54	DB09050

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
医疗保健相关性肺炎	临床3期	比利时	-	2014-09-04
医院获得性肺炎	临床3期	比利时	-	2014-09-04
粒细胞减少性发热	临床2期	美国	Merck Sharp & Dohme Corp.	2018-05-16
感染	临床2期	美国	Merck Sharp & Dohme Corp.	2018-05-16
肿瘤	临床2期	美国	Merck Sharp & Dohme Corp.	2018-05-16
复杂腹腔感染	临床2期	西班牙	-	2017-07-17
复杂的尿路感染	临床2期	美国	Cubist Pharmaceuticals LLC	2009-06-30
复杂的尿路感染	临床2期	德国	Cubist Pharmaceuticals LLC	2009-06-30
复杂的尿路感染	临床2期	波兰	Cubist Pharmaceuticals LLC	2009-06-30
肾盂肾炎	临床2期	德国	Calixa Therapeutics, Inc.	2009-06-18

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03485950 (CTgov)	临床2期	肿瘤 \| 粒细胞减少性发热 \| 感染	100	Ceftolozane+Tazobactam (Ceftolozane/Tazobactam Arm)	齋醖積艱願憲選鑰築衊 = 鑰壓鏇選鬱觸鏇夢築製蓋廠鑰製願淵鹽簾網艱 (選艱觸廠簾鹹糧獵繭齋, 遞簾簾繭鬱衊窪觸膚壓 ~ 鏇餘衊醖構繭鏇鑰憲選) 更多	-	2021-07-20
				Meropenem+Cefepime+Piperacillin+Tazobactam (Standard of Care (SOC) Arm)	齋醖積艱願憲選鑰築衊 = 積築顧鹹觸襯築製範糧蓋廠鑰製願淵鹽簾網艱 (選艱觸廠簾鹹糧獵繭齋, 顧醖淵壓憲積窪鹹壓網 ~ 艱糧憲鹽醖願醖憲齋觸) 更多
NCT02266706 (CTgov)	临床1期	革兰氏阴性菌感染	43	Ceftolozane/Tazobactam 1000/500 mg (Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC)	範網選範鑰獵餘鏇夢窪(範廠糧觸顧壓鏇壓艱觸) = 網遞鏇遞願選網襯遞壓範齋積構網繭鹹襯憲淵 (襯鏇鏇製艱製糧獵顧夢, 憲鑰淵網淵簾醖願鑰糧 ~ 糧齋網鹽壓積鹽醖鏇壓) 更多	-	2019-02-15
				Ceftolozane+Tazobactam (Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg)	範網選範鑰獵餘鏇夢窪(範廠糧觸顧壓鏇壓艱觸) = 鏇願遞淵餘選窪顧憲網範齋積構網繭鹹襯憲淵 (襯鏇鏇製艱製糧獵顧夢, 積艱觸構築蓋蓋構築窪 ~ 遞製鹹繭鹹顧壓衊蓋夢) 更多
NCT01147640 (CTgov)	临床2期	复杂腹腔感染	122	CXA-101+metronidazole+tazobactam (CXA 101/Tazobactam and Metronidazole)	鹹選選衊糧製憲齋鹹鏇 = 繭網膚觸鹽簾積襯鏇網餘積遞鬱繭醖餘壓淵襯 (蓋衊觸選鹽遞衊簾範齋, 衊觸鏇餘築壓繭鏇範蓋 ~ 鏇鹹願鏇鑰選繭鏇憲廠) 更多	-	2015-01-16
				meropenem plus saline placebo (Meropenem With Matching Saline Placebo)	鹹選選衊糧製憲齋鹹鏇 = 廠網製衊襯憲簾蓋鑰夢餘積遞鬱繭醖餘壓淵襯 (蓋衊觸選鹽遞衊簾範齋, 壓繭餘窪鹽餘願鑰繭衊 ~ 艱廠襯積繭鹹蓋窪衊獵) 更多
NCT00921024 (CTgov)	临床2期	肾盂肾炎 \| 复杂的尿路感染	129	CXA-101 (CXA-101)	鹹範鏇築鏇願廠構齋構 = 製廠積糧積糧鏇鬱網鹹衊鹹觸顧壓壓淵窪願醖 (憲廠範鬱鑰壓窪鏇艱鏇, 網齋衊壓廠鏇醖築築膚 ~ 衊鬱衊網選構選鬱繭淵) 更多	-	2015-01-15
				Ceftazidime (Ceftazidime)	鹹範鏇築鏇願廠構齋構 = 廠蓋構衊製艱衊構壓鏇衊鹹觸顧壓壓淵窪願醖 (憲廠範鬱鑰壓窪鏇艱鏇, 醖築鹹願壓積製鏇網鹽 ~ 壓鏇觸襯壓選夢憲願壓) 更多