This study is a two-arm, pragmatic, open-label, randomized clinical trial to determine the efficacy of Therapeutic Drug Monitoring (TDM) in preventing premature discontinuation of Linezolid (LZD) in participants with Rifampicin-resistant tuberculosis (RR-TB). Following the initiation of treatment, participants will be monitored throughout the approximate 6-month duration of RR-TB therapy.

开始日期2026-03-01

申办/合作机构

Albert Einstein College of Medicine, Inc.

[+4]

CTRI/2025/12/099965

/ Not yet recruiting临床3期IIT

ESCALATE 2: Linezolid As An Add-On Treatment In The Intensive Phase OfTubercular Meningitis. A Randomised Controlled Trial - ESCALATE 2

开始日期2026-01-15

申办/合作机构

Indian Council of Medical Research

NCT07301294

/ Not yet recruiting临床4期IIT

Microbiological Characteristics of Biofilm on Double J Ureteral Stents After Lithotripsy: A Randomized Controlled Trial

Indwelling Double J (DJ) ureteral stents are commonly used following lithotripsy to ensure adequate urinary drainage and prevent obstruction. However, stent-related biofilm formation remains a significant clinical problem, contributing to infection, encrustation, patient discomfort, and stent failure. Biofilms consist of microbial communities embedded within an extracellular polymeric substance (EPS), which protects microorganisms from host defenses and antimicrobial agents.
Antibiotic therapy alone may be insufficient to eradicate established biofilms due to poor penetration into the EPS matrix. Linezolid is a potent antibiotic with activity against gram-positive organisms commonly implicated in urinary tract colonization and penetrate and effectively act against bacterial biofilms. Mucolytic agents, by disrupting the biofilm matrix, may enhance antimicrobial penetration and reduce biofilm burden.
The combination of an antibiotic with a mucolytic agent may therefore provide superior biofilm reduction compared to either approach alone or no treatment.

开始日期2026-01-01

申办/合作机构

Menoufia University

100 项与利奈唑胺相关的临床结果

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100 项与利奈唑胺相关的转化医学

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100 项与利奈唑胺相关的专利（医药）

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6,837

项与利奈唑胺相关的文献（医药）

2026-12-31·RENAL FAILURE

Protective effects of adenosine triphosphate, thiamin, thiamin pyrophosphate, and their combination against linezolid-induced renal injury and lactic acidosis in rats

Article

作者: Suleyman, Halis ; Mendil, Ali Sefa ; Yucel, Nurinisa ; Yavuzer, Bulent ; Mammadov, Renad ; Admis, Ozlem ; Suleyman, Bahadir ; Altuner, Durdu

Linezolid, an oxazolidinone antibiotic effective against Gram-positive pathogens, may cause nephrotoxicity and lactic acidosis during prolonged therapy. This experimental study investigated the protective effects of adenosine triphosphate (ATP), thiamin, thiamin pyrophosphate (TPP), and their combination (ATTP) on linezolid-induced renal injury and lactic acidosis in rats. Thirty-six male Wistar rats were randomly divided into six groups (n = 6): healthy control (HG), linezolid only (LZD), ATP+linezolid (ATLZD), thiamin + linezolid (TLZD), TPP+linezolid (TPLZD), and ATP+thiamin + TPP+linezolid (ATTPL). Linezolid (125 mg/kg, orally) was administered twice daily, while ATP (4 mg/kg), thiamin (20 mg/kg), and TPP (20 mg/kg) were given intraperitoneally once daily for 28 days. At the end of treatment, kidney tissues were examined for oxidative stress markers [malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT)] and histopathology, and blood samples were analyzed for blood urea nitrogen (BUN), creatinine, and lactate. Linezolid increased oxidative stress, suppressed antioxidants, and elevated BUN, creatinine, and lactate levels. ATP partially improved the oxidative balance in renal tissue but failed to prevent hyperlactatemia and impaired renal function. Thiamin did not produce significant changes. TPP markedly improved oxidative stress markers and reduced renal dysfunction. The triple combination provided the most pronounced protection, restoring antioxidant defenses, kidney function, and lactate levels to near-control values. Histopathological evaluation revealed marked tubular degeneration, interstitial hemorrhage, and mononuclear cell infiltration in the linezolid group, which were markedly improved by TPP and combination therapy. These findings indicate that TPP protects against linezolid-induced nephrotoxicity and lactic acidosis, with its efficacy further enhanced by ATP.

2026-12-01·BRAZILIAN JOURNAL OF MICROBIOLOGY

Enterotoxin and biofilm producing Staphylococcus aureus and MRSA isolates from animal source foods sold in Assam

Article

作者: Av, Vishnu Raghavendran ; O R, Vinodh Kumar ; Dhanze, Himani ; Rawat, Shriya ; Kolhe, Rahul ; Dubal, Zunjar Baburao ; Kumar, Rajiv Ranjan ; Viswas, K N

Animal-derived foods (ADF) are carriers of toxin-producing multidrug-resistant (MDR) S. aureus strains, posing a global food safety risk. We evaluated the toxin and biofilm production capabilities of S. aureus isolates from ADF marketed in Assam, India. Of the 138 staphylococcal isolates, 29 (21.01%) were identified as S. aureus, mostly isolated from raw milk. Resistance to chloramphenicol (13.79%), erythromycin (68.96%), penicillin (93.10%), enrofloxacin (20.68%), tetracycline (55.17%), trimethoprim-sulfamethoxazole (20.68%), linezolid (6.89%), cefoxitin (55.17%), and oxacillin (48.27%) was noted. Approximately 82.75% isolates were MDR, whereas 27.58% carried mecA gene, indicating methicillin-resistant S. aureus. PCR toxinotyping revealed pvl (20.69%), sea (37.93%), and sed (17%) genes. Additionally, 6.89% isolates harbored seb, sei, and tst genes; all lacked eta, etb, see, seg genes. A significant difference (P < 0.05) was observed in sea and sei genes across food sources. Biofilm-forming genes were detected as icaA (65.51%), icaB (34%), icaC (48.27%), icaD (27.58%), clfA (51.72%), clfB and fnbA (44.82%). At least one biofilm-associated gene was found in 72.41% of isolates, while two or more genes were present in 80.95%. Approximately 87.5% of mecA-positive isolates contained at least one biofilm-associated gene. A significant difference (P < 0.05) was noted in icaA, icaD, clfB, and fnbA across the different ADF sources.

2026-06-01·Archivos Argentinos de Pediatria

Brain abscess caused by Mycobacterium avium complexin an adolescent with an inborn error of immunity

Article

作者: Squassi, Isabel ; Garrigue, Carolina ; Santelli, Luciana ; Feuerstein, Manuel ; Gonçalves Neiva Novo, María C ; Manonelles, Gabriela ; Gómez Raccio, Andrea

Mycobacterium avium complex (MAC) infections of the central nervous system are rare and represent a diagnostic challenge, especially in immunocompromised patients. Comprehensive management requires early diagnosis, prolonged antimicrobial treatment, and, in some cases, neurosurgical interventions. We present the case of a 16-year-old patient with an inborn error of immunity caused by a variant in the NFKB1A gene, who consulted for paresis of the left upper limb. A diagnosis of brain abscess was made using central nervous system (CNS) imaging, and the etiological agent was confirmed by neurosurgical biopsy culture after an unfavorable clinical course with initial empirical treatment. The patient was treated with rifampicin, ethambutol, levofloxacin, linezolid, clarithromycin, and high-dose dexamethasone, achieving significant clinical and radiological improvement after prolonged treatment.

395

项与利奈唑胺相关的新闻（医药）

17 小时之前

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Nat Rev Microbiol│细菌代谢在抗菌药物耐药性中的作用

导读细菌代谢与抗生素治疗之间存在复杂的双向关系。一方面，抗生素通过靶向细胞代谢发挥作用。另一方面，细菌代谢状态深刻影响抗生素生物学特性——涵盖药物疗效、抗菌素耐药性（antimicrobial resistance，AMR）演化及耐药机制。鉴于AMR对全球现有抗生素库及传染病治疗能力构成重大威胁，阐明此类关系对改善公共健康至关重要。然而，量化代谢对抗生素活性及耐药性演化的贡献仍具挑战。本综述系统探讨代谢与抗生素治疗间的多维相互作用。首先阐述抗生素靶向代谢的作用机制，继而聚焦代谢对抗生素生物学三大核心领域的独特影响——药物疗效、AMR进化路径及耐药分子机制，最后评述代谢在临床实践中的相关性，并展望基于代谢的个体化抗菌治疗策略。深入解析这些关联对全球科学界应对AMR危机、开发新型有效疗法具有关键意义。论文ID 原名：The role of bacterial metabolism in antimicrobial resistance 译名：细菌代谢在抗菌药物耐药性中的作用期刊：Nature Reviews Microbiology IF：103.3 发表时间：2025.2 通讯作者：Allison J. Lopatkin 通讯作者单位：美国罗切斯特大学 DOI号：10.1038/s41579-025-01155-0 目录 1 引言 2抗生素对代谢的影响 3代谢对抗生素的影响 4 哺乳动物宿主的临床后果 5未来展望主要内容 1 引言抗生素的发现堪称现代医学最具变革性的成就之一，其应用使人类平均寿命延长逾20年。抗生素不仅彻底革新了细菌感染的治疗方式，更为复杂医疗程序（如化疗与器官移植）及常规护理（如拔牙与分娩）提供了关键感染控制保障。作为抵御常见急性感染的首道防线，抗生素可高效治愈化脓性链球菌所致咽炎、金黄色葡萄球菌引发的皮肤感染以及淋病奈瑟菌导致的性传播疾病。抗生素的广泛使用也催生了抗菌药物耐药性（antimicrobial resistance，AMR）——细菌在临床抗生素浓度下仍能存活增殖的现象，导致治疗失效。临床与农业领域的抗生素滥用加剧了AMR流行，现已被全球公认为重大健康危机。随着多重耐药菌激增及有效抗生素减少，预测表明2025至2050年间全球将有超1.69亿人死于AMR相关感染。细菌AMR主要由遗传机制驱动。通过自然遗传变异克隆扩增或移动遗传元件水平转移获得。无论获取方式如何，AMR机制通常可分为三大类：改变药物转运动力学，降低细胞内药物浓度；直接抗生素灭活，通常由酶水解介导；以及抗生素靶位点的修饰，如青霉素结合蛋白中阻止药物结合的突变。总的来说，这些机制严重威胁现有抗生素库的有效性，尤其在新药研发滞后于细菌进化速度的背景下。细菌对抗生素的应答机制仍是核心研究领域。最新研究表明细菌代谢——涵盖所有分解与合成代谢过程（基因、通路、代谢物及互作网络）——不仅受AMR影响，更深度调控耐药性形成。作为细胞功能的核心引擎，代谢为基因表达、蛋白合成、防御机制等关键活动提供能量与资源。这种复杂性使代谢成为抗生素治疗与应答各环节的调控枢纽。细菌代谢与抗生素治疗存在双向互作。代谢状态影响药物疗效，抗生素亦改变代谢通路。该互作揭示靶向代谢对抗AMR的巨大潜力。外源代谢物导入或特定通路上调可恢复耐药菌对抗生素的敏感性。这些发现为应对AMR提供了新视角，凸显代谢此前被低估的调控价值。鉴于细菌代谢与抗生素应答研究的迅猛发展，本综述旨在系统阐述代谢对抗生素的多维影响机制（图1）。首先总结抗生素对代谢的重编程作用，继而探讨代谢对药物疗效、AMR进化动力学及耐药机制的反向调控，最后评述代谢在哺乳动物宿主中的临床相关性及基于代谢疗法的抗AMR潜力。本文强调深入解析代谢-抗生素互作的必要性，并为下一代个体化抗菌疗法提供理论框架。图1. 抗生素与代谢之间的相互作用。细菌代谢状态、宿主环境和药物作用机制共同影响细菌对抗生素的反应。反过来，抗生素可以直接改变细菌的代谢状态，进一步塑造这种相互作用。这种双向关系可以通过四个主要方面来理解：抗生素疗效、抗菌素耐药性（AMR）机制、AMR演变和代谢失调。抗生素疗效的调节可能表现在采用不同代谢生长生理学或表型代谢休眠状态（例如生物膜）的细菌中。抗生素也可能根据病原体或宿主的代谢环境表现出不同的疗效。AMR机制通过主要（例如代谢旁路）、次要（例如，靶突变改变的营养偏好）或间接（例如，改变的代谢基因表达水平）通路影响代谢。代谢失调可能通过改变ATP水平、三羧酸循环（TCA）或其他代谢细胞过程（例如细胞壁生物合成）而发生。AMR的进化可以通过改变选择动力学、水平基因转移（HGT）过程或de novo突变。 2 抗生素对代谢的影响抗生素作为靶向细菌细胞过程的小分子化合物，通过干扰生长或存活发挥抗菌作用。依据作用模式可分为杀菌剂（诱导细胞死亡）和抑菌剂（抑制细胞生长）。近期研究揭示两类药物对代谢的不同扰动机制，为阐明其作用机制提供新视角（图2）。图2.杀菌剂和抑菌剂利用新陈代谢来发挥其功能。杀菌剂在抑制初始靶点后，通过刺激代谢活动诱导细胞死亡，包括上调应激反应网络和电子链以及三羧酸循环（TCA）循环活性。抑菌剂（下图）抑制细胞生长。经典情况下，在抑制初始靶点后，生长抑制通过下调关键细胞过程发生，包括糖酵解途径和TCA循环。大分子生物合成和蛋白质翻译过程也可能受到限制，导致细胞内能量积累，最终导致细胞停滞。通常，杀菌抗生素通过抑制基本的细胞靶点诱导细胞死亡，除了一些例外情况，这些靶点通常与DNA复制（例如氟喹诺酮类）、蛋白质合成（例如氨基糖苷类）和细胞壁合成（例如β-内酰胺类、头孢菌素类）有关。在每种情况下，产生的细胞内损伤通常与药物的作用模式一致。例如，氟喹诺酮类药物抑制DNA旋转酶和拓扑异构酶IV，导致有毒的双链DNA断裂；氨基糖苷类药物靶向30S核糖体亚基，导致蛋白翻译出错和毒性应激。除直接损伤外，其诱导代谢稳态失衡是细胞死亡的第二层机制。杀菌剂暴露会立即触发应激反应网络的上调，包括SOS和严重反应。同时因修复系统能量需求增加，导致电子传递链、TCA循环及碳氧化途径失调。与这些影响一致，在杀菌暴露后，在不同的细菌物种中观察到ATP水平、耗氧率和活性氧物种的增加。例如，暴露于氨苄青霉素的大肠杆菌的单细胞RNA测序显示出TCA循环、甘氨酸代谢和糖酵解基因表达失调的明显迹象，与群体水平的测量结果一致。同样，多项研究报告称，用一系列抗生素处理牛分枝杆菌会增加细胞内ATP水平。有趣的是，经抗生素处理后1.5小时内ATP水平可激增4-5倍。最终，这种代谢失调会导致细胞毒性，再加上最初的靶点抑制，最终导致细胞死亡。我们注意到，所描述的每个方面对细胞死亡的贡献程度在历史上一直存在争议，并且可能因条件而异。根据代谢限制，细胞损伤通过不同的途径发生。对于革兰氏阳性和革兰氏阴性细菌的喹诺酮类、氨基糖苷类和β-内酰胺类治疗，有氧条件下的治疗通常与TCA循环和NADH耗竭引起的氧化损伤有关。相比之下，在厌氧条件下，相同的抗生素会促进糖酵解的增加——积累中心碳代谢物（例如葡萄糖和丙酮酸）——并产生不同的反应性代谢副产物（例如反应性亲电物种）。此外，尽管完全不同的杀菌类别最终会失调中枢代谢，但中间途径差异很大，这受到抗生素特异性作用机制的影响。例如，β-内酰胺处理诱导细胞壁合成和降解的无效循环，从而通过特定的细胞壁合成机制消耗细胞资源并增强杀伤性。此外，对于环丙沙星和氨苄西林的毒性，嘌呤生物合成需求的增加被发现是关键。庆大霉素的情况并非如此，这表明核苷酸限制可能对某些药物具有特异性，但对其他药物则没有。仍然需要更深入地了解药物特异性代谢途径及其与主要药物靶点的相互作用。杀菌剂通过上调能量代谢相关中枢通路（如电子传递链、三羧酸循环）发挥作用，而抑菌剂则通过限制能量利用、大分子生物合成及蛋白质翻译降低代谢活性。这种生长抑制可诱导独特代谢状态。氯霉素与利奈唑胺治疗导致能量代谢物异常积累；蛋白质组学分析证实金霉素显著下调糖酵解、糖异生、丙酮酸代谢及三羧酸循环活性。值得注意的是，抑菌剂在高浓度时可呈现杀菌效应（反之亦然），此现象模糊了两类药物的功能界限。当前学界对代谢抑制是否直接引发细胞死亡，或特定条件触发“类杀菌”激活过程尚未达成共识，需深入研究以阐明其动态机制。抗生素治疗的潜在后果是形成耐受性持留菌，这在慢性感染中很常见（框1）。传统认为持留菌随机产生或由环境压力诱导，使细菌亚群进入代谢惰性状态。其形成机制与SOS反应、严谨反应、（p）ppGpp信号传导及ATP耗竭密切相关，毒素-抗毒素系统、转运RNA甲基化修饰和蛋白质降解异常亦参与调控。抗生素治疗可通过抑制转录、翻译等关键过程增加持留菌形成频率，亚致死浓度还能激活应激反应、次级信使通路及毒力因子促进持留态转化。关于持留菌形成机制的详细讨论已在其他地方进行了综述。总体而言，抗生素显著重塑细胞代谢状态，而这些代谢变化可反馈增强药物作用，进而差异化影响细菌生长、抗生素选择压力及长期进化适应。因此，除解析抗生素治疗后代谢改变外，亟需在药物暴露前/期间表征细胞代谢状态，以深入理解微生物存活机制及后续抗菌药物耐药性演化路径。 3 代谢对抗生素的影响鉴于抗生素治疗对细菌代谢的显著影响，治疗前细胞的代谢状态亦可调控抗生素反应，甚至通过代谢途径调节药物的预期作用机制及下游代谢失调。这种互作关系在结核分枝杆菌中尤为显著——其独特的代谢特征与多样化抗生素治疗方案共同塑造了复杂的耐药表型（图3）。近年来，相关机制研究已拓展至其他病原体与环境。本文通过解析代谢对抗生素疗效、耐药性演化及耐药机制的三重影响，系统阐述代谢在细菌抗生素应答中的核心作用。图3. 代谢调控结核分枝杆菌抗生素耐药性、耐受性与致死率的独特机制。A，杀菌抗生素可激活SOS反应通路。抗生素激活RecA蛋白，RecA蛋白活化后抑制LexA阻遏蛋白，诱导易错聚合酶等SOS基因表达，导致抗生素靶点突变及耐药性产生。B，抗生素改变三羧酸循环（TCA）活性。治疗期间异柠檬酸裂解酶（ICL）激活乙醛酸分流，降低还原性TCA循环活性，伴随代谢整体抑制及活性氧（ROS）解毒基因（如katG、furA、trxB1）表达下调，共同赋予细菌耐受性。C，抗生素特异性机制。贝达喹啉通过激活转录因子Rv0324/Rv0880，上调毒力、解毒及细胞壁相关基因表达诱导耐受性（Ca）；异烟肼则通过KatG和NAD⁺结合抑制分枝菌酸生物合成关键酶InhA，阻断细胞壁合成导致死亡（Cb）。D，靶向多代谢途径增强致死率。贝达喹啉激活乙醛酸分流与ATP合酶，迫使细菌依赖糖酵解及底物水平磷酸化供能；抑制后者可显著提升贝达喹啉致死效应。E，代谢物辅助增效。半胱氨酸进入细胞转化为胱氨酸产生活性氧，与抗生素联用可通过ROS累积协同增强杀菌效果。 3.1 抗生素疗效确定代谢在抗生素致死率中的作用历来具有挑战性。由于代谢与生长密切相关，改变代谢活动的条件也会影响生长速率。此外，生长和抗生素疗效之间的关系更容易量化，因此以前一直是一个主要焦点。最常见的是，据报道，细菌生长率与杀菌抗生素的效率成正比。也就是说，杀菌抗生素通常被证明对快速增长的细菌种群最有效。然而，生长速率和代谢活动并不是普遍相关的，之前的研究经常将生长效应与代谢效应混为一谈。最近的研究发现，这种关系更加复杂。例如，细胞生长速率和细胞死亡之间的线性关系取决于环境条件，突出了这种关系的生理约束；通过改变抗生素类型、碳源和盐浓度来改变环境可以改变斜率或截距的大小。此外，充分的代谢刺激已被证明可以促进抗生素杀死不生长的持久细胞，从而表明代谢的独特作用。这些发现表明，虽然在某些条件下生长可能是抗生素疗效的指标，但代谢对抗生素疗效的独特影响值得独立研究。 3.2 增强抗生素活性多项证据表明细胞代谢状态独立于生长速率直接调控杀菌抗生素疗效。在多种条件下，抗生素活性与代谢状态的相关性显著高于生长速率。同样，成功根除大肠杆菌和金黄色葡萄球菌已被证明需要代谢组重塑。这种代谢效应也解释了既定的抗生素剂量-反应关系。例如，接种物效应——一种众所周知的现象，描述了随着细胞密度的增加杀菌效果的降低——也基于代谢，更具体地说，是ATP浓度和密度抑制之间的权衡。鉴于已观察到不同抗生素类别和临床环境中的接种物效应，本研究凸显代谢在驱动体内抗生素应答中的核心作用。与这些发现一致，特定代谢物刺激可药物特异性提升抗生素致死率。在某些情况下，这些效应可能部分可以通过质子动力（PMF）的代谢刺激来解释。特别是对于带正电荷的氨基糖苷类，PMF增加了细胞内药物摄取，从而提高了抗生素的致死率。例如，添加糖酵解代谢物（如葡萄糖、甘露醇和果糖）可以提高庆大霉素对耐抗生素大肠杆菌和金黄色葡萄球菌的疗效。值得注意的是，这些观察结果在体内是可重复的，庆大霉素与甘露醇联合使用使导管生物膜的存活率降低了近1.5个数量级，并阻断肾脏感染扩散。虽然这些结果说明了代谢刺激在病原体治疗中的益处，但它们也强调了单独研究代谢的必要性。例如，细胞呼吸与PMF驱动的药物转运在氨基糖苷类致死率中的相对贡献仍未完全被理解。除了增强药物摄取外，刺激代谢活动还可以通过次级代谢效应增强抗生素疗效。例如，将TCA循环中间体富马酸盐与抗生素妥布霉素结合，可杀死与囊性纤维化相关的机会致病菌铜绿假单胞菌。从机制上讲，富马酸盐通过TCA循环激活细胞呼吸并刺激质子动力。值得注意的是，即使在存在药物进口的情况下，抑制TCA循环也能恢复抗生素耐受性，这表明TCA循环活性对于代谢物补充和妥布霉素发挥作用至关重要。这些发现强调了下游代谢过程（独立于药物摄取）在驱动抗生素致死率方面的关键作用。同样，激活结核分枝杆菌的呼吸已被证明可以预防耐药性和耐药性的出现。添加小巯基使结核分枝杆菌保持活跃的代谢状态，产生“氧化爆发”，增加氧气消耗和活性氧的产生，促进细胞死亡。 3.3 降低抗生素疗效虽然高代谢活性可以加强抗生素治疗，但低代谢活性可以防止抗生素暴露。在许多病原体和环境中都观察到了这些保护作用，并且可以通过多种机制发生。例如，富马酸通过激活TCA循环提高了铜绿假单胞菌的氨基糖苷类疗效，而代谢产物乙醛酸则诱导了抗生素耐受。保护作用归因于乙酰辅酶A通过乙醛酸分流器的转移抑制了细胞呼吸。同样，结核分枝杆菌的抗生素耐受是通过抑制TCA循环代谢来介导的。此外，蛋白质组学分析证实溶藻弧菌的中心碳代谢抑制可增强左氧氟沙星耐受性。低代谢状态可能是对环境刺激的反应，如营养剥夺，这会降低抗生素的疗效。例如，限制特定氨基酸通过下调能量产生、戊糖磷酸和核苷酸代谢来保护鲑鱼免受氨苄青霉素的侵害，而不影响生长速度或抗性基因表达。这些影响在生物膜中进一步加剧，细菌存在于各种异质的代谢休眠状态中（图4）。在生物膜内，细菌的抗生素耐受性比治疗所需的浓度高出数百到数千倍。虽然生物膜结构本身可以防止抗生素渗透，但营养限制导致的有氧代谢减少主要有助于抗生素耐受性。营养恢复可以逆转这种效应，使生物膜细胞对抗生素敏感。图4. 生物膜的独特性质通过改变新陈代谢赋予抗生素耐药性。A，与抗生素治疗相关的生物膜的生化特性。生物膜是附着在表面的细菌群落，周围有一层外聚物质（EPS）。EPS主要由细胞外DNA（eDNA）、菌毛和多糖组成。尽管可以形成携带营养物质和氧气进入生物膜内层的间隙空隙，但整体营养物质和氧运输受到EPS的限制（Aa部分）。靠近生物膜表面的细菌会经历更多的营养和氧气，而那些靠近底部的细菌对这两种物质的获取有限，因此对抗生素的耐受性增强（部分Ab）。B，抗生素对生物膜群落的影响。抗生素处理后，生物膜中代谢休眠的持久细胞的存在增加（Ba部分；紫色）；这些细胞对抗生素的耐受性更强。生物膜成员之间的结合频率和效率增加，使赋予抗性的基因数量迅速增加（Bb部分）。生物膜中的群体感应增强（Bc部分）。这可能导致代谢途径的重新连接，包括葡萄糖输入、戊糖磷酸途径和核苷酸合成。这些变化可能会增加抗生素耐受性。使用代谢物增加生物膜中的代谢可以提高抗生素的致死率（部分Bd）。群体行为相关表型亦与独特代谢状态关联。例如，铜绿假单胞菌等群集细菌表现出暂时的耐受性，而cbrA等代谢基因与毒力和抗性表型有关。细菌群体运动会带来高代谢负担，导致与抗生素疗效相关的通路整体下调，包括糖酵解和丙酮酸异化、TCA循环和氨基酸生物合成。这些发现强调，在一些复杂的环境中，代谢和AMR之间的复杂相互作用尚未完全阐明。耐受性也与密度依赖信号有关，如群体感应（quorum sensing，QS）。QS允许细菌采取合作状态，并影响生物膜形成、毒力因子合成和群集。QS还通过下调葡萄糖摄取、戊糖磷酸通路和从头核苷酸生物合成来调节中枢代谢。这引发了类似的问题，即代谢对耐药性和分组细菌状态的影响范围。这些复杂互作机制亟待深入解析，尤其需阐明代谢在多通路调控耐药性中的核心作用。 3.4 新型抗菌药物耐药性的演变抗生素暴露后，代谢通过直接与间接途径驱动AMR演化。杀菌抗生素通过刺激氧化应激、激活SOS反应及DNA修复机制显著提高突变率，增加耐药突变产生概率。例如氨苄西林、环丙沙星或卡那霉素（而非抗菌肽）处理使突变率提升3-4倍，SOS介导的突变对铜绿假单胞菌和结核分枝杆菌临床株及生物膜中的AMR发展至关重要。除了新发突变，AMR还通过水平基因转移（horizontal gene transfer，HGT）演化，其中接合性质粒转移（细胞直接接触传递）通过接合、转化和转导发生，是耐药性传播的核心机制。质粒编码自我复制及多重AMR基因，即使无抗生素选择压力仍可维持耐药性。生物膜环境显著促进接合作用，加速抗性基因扩散。结合效率（动力学转移速率）受细胞代谢状态的影响，因为结合是能量密集型的（图5）。高碳浓度和活跃的生理状态可以大幅提升质粒转移动力学速率。转移后，与质粒再循环和宿主建立相关的能量需求带来了短暂的代谢成本，称为质粒获取成本，这在代谢效率高的细胞中更高，可能是由于能量限制。重要的是，这些成本与没有质粒的生长速度无关。因此，与生长分开，代谢会影响抗生素耐药性侵入新环境的程度。质粒对宿主施加了长期的能量需求（维护、拷贝数等）。这种适应成本主要来自与蛋白质产量增加相关的代谢负担，并限制了质粒传播的范围和轨迹。这些短暂的（获取）和长期的（适应）成本都会导致微生物群落的潜在竞争优势或劣势，从而导致进化结果。图5. 代谢通过接合作用促进抗微生物耐药性的进化。a，代谢状态调控接合效率。碳代谢增强可提升质粒转移动力学速率；群体感应通过代谢重编程维持高接合效率，同时增强细菌毒力协作。b，瞬时采集成本取决于细胞的代谢效率。接合后，新获得的质粒通过激活SOS反应和失调质粒调控网络对细胞产生短期破坏。这种细胞内扰动导致新的携带质粒的宿主菌株出现生长缺陷，称为获取成本。通过改变营养成分来操纵细胞的代谢状态可以调节获取成本。c，代谢对结合质粒竞争力的长期影响。与无质粒宿主（右细胞）相比，携带质粒的宿主（左细胞）也可能经历长期的生长缺陷或负担（即质粒适应性成本），特别是在没有抗生素选择的情况下。适应成本影响代谢的不同途径。除了结合，代谢也可能影响其他HGT模式。例如，调节新陈代谢的QS也调节细菌的能力。通过这种方式，代谢可能与为细菌提供修复受损基因或获得新的有利特征的机制有关。同样，转导取决于细菌的生长；这引发了关于不同细菌代谢状态如何影响转导噬菌体感染细菌的能力的问题。此外，代谢状态也可以作为药物耐受和遗传耐药性之间的表型桥梁。休眠通常与抗生素耐受状态有关，已被证明会促进随后的真正耐药性，并先于耐药性演变。此外，延长生存期也可能有利于随后的基因转移事件，尽管其直接联系仍有待观察。耐药性随机性使代谢失调与AMR的因果关联研究面临挑战。尽管如此，越来越多的证据突显了代谢在塑造AMR进化中的作用。例如，可转移质粒上代谢基因的存在被证明可以防止抗生素治疗，拓宽了直接抗生素选择下的质粒和代谢基因可能赋予AMR的背景。这是通过调节质粒相关的代谢作用还是直接通过基因功能本身发生的，还有待观察。此外，碳和能量代谢被发现可以在两种不同的营养条件下限制AMR对三种作用机制不同的抗生素的进化。对190个进化种群中代谢物的综合分析表明，碳和能量代谢在获取速度和模式方面都强烈限制了抗生素耐药性的进化。未来需深入解析特定代谢通路在AMR大背景下的调控网络。。 3.5 一级和二级抗菌药物耐药机制众所周知，抗生素通过选择耐药菌株在致死浓度下存活，经典机制包括靶点修饰、药物灭活及转运改变。近年研究表明代谢在AMR中发挥双重作用：既可直接作为耐药决定因素被抗生素选择，亦可通过代谢效应补充或放大经典耐药机制（图6）。图6. 抗菌药物耐药性的经典和代谢调控机制。细菌染色体或质粒编码的经典耐药机制（红色）包括：靶点修饰、酶介导药物灭活及抗生素摄取减少，这些机制可能伴随间接代谢效应（如孔蛋白改变营养吸收）。代谢直接驱动AMR的机制（蓝色）涵盖：差异代谢基因表达、替代通路激活及代谢基因插入。生物膜与孔蛋白等结构特征亦通过间接代谢作用影响AMR——生物膜提供物理保护并形成异质代谢状态；孔蛋白表达下调同时减少营养与抗生素摄取。核心代谢基因突变或表达水平改变可导致体外AMR。在某些情况下，耐药性发生的机制是明确的，因为受影响的代谢基因与特定的药物类型直接相关。例如，由于甲氧苄啶和磺胺甲恶唑（trimethoprim and sulfamethoxazole，TMP-SMX）共同抑制叶酸的合成，叶酸是核苷酸生产的关键前体，对这种常见药物组合的耐药性直接影响菌株的代谢。这种阻力可能以多种方式出现。例如，在金黄色葡萄球菌、肺炎链球菌和流感嗜血杆菌中，编码二氢叶酸还原酶的dhfr基因突变可导致甲氧苄啶耐药性。令人担忧的是，最常见的dhfr变体允许药物浓度比抑制易感分离株所需的浓度高1000倍。TMP-SMX耐药性也可能通过过量产生二氢叶酸还原酶（dihydrofolate reductase，DHFR）或二氢蝶酸合酶（dihydropteroic acid synthase，DHPS）的酶促药物靶点而发生。此类“代谢旁路”经DNA启动子突变激活，有效抵消药物对叶酸合成的抑制。尽管细菌代谢的主要作用直接干扰药物与靶点的相互作用，但其次要作用也可以防止抗生素治疗，尽管是间接的。由于不同抗生素的作用往往集中在共同的下游代谢通路上，部分代谢机制可提供广谱保护。例如，与中心碳和能量代谢相关的基因与大肠杆菌对三种杀菌抗生素的耐药性有关。事实上，这些基因的过表达增加了耐药性，突变本身在致病基因组中非常普遍，突显了它们的临床相关性。其他与药物无关的方法也得出了类似的结论。例如，沙门氏菌基因组的高度准确的耐药性预测确定了几个以前未被重视的代谢基因在耐药性中的潜在作用，包括那些参与氧化应激和电子转运的基因。同样，葡萄糖利用特异的代谢抗性赋予对羧苄青霉素与环丙沙星的交叉耐药。除了代谢特异性变化外，经典AMR机制亦可改变细胞代谢状态，此类代谢变化被视为耐药的次要后果，但其在AMR表型中的直接贡献尚未明确。例如调控元件CbrAB/envZ-ompR突变通过下调孔蛋白表达减少抗生素摄取，导致多粘菌素B、环丙沙星等药物疗效降低。孔蛋白表达改变同时影响氨基酸、糖及离子运输，但药物摄取对营养动力学的具体作用仍有待验证。某些耐药机制存在意外代谢权衡：利福平耐药基因rpoB突变在赋予耐药性的同时促进β-葡萄糖苷利用。综上，代谢在AMR中的完整作用仍与经典机制混为一谈。尽管已经确定了AMR的一些有趣的代谢机制，但这些关系充满了未解之谜；众所周知，代谢网络是复杂的、冗余的和补偿性的。因此，简化模型（如“低呼吸/代谢活性赋予保护”）难以全面解释耐药产生。该概括未涵盖所有细菌反应，例如大肠杆菌、铜绿假单胞菌等群体中生长较快菌株反而受大环内酯类保护（无基因突变参与）。这些矛盾凸显基础认知与方法学局限——传统技术（如波动分析）无法同步捕捉抗生素诱导突变、耐药进化及群体行为等多维动态。突破此瓶颈需发展新一代研究方法以揭示代谢-AMR的深层互作网络。这些缺点表明，在未来几十年里，仍有许多方法论工作要做。 4 哺乳动物宿主的临床后果考虑到宿主环境，抗生素疗效和细菌对抗生素治疗的反应似乎越来越复杂。作者希望读者阅读其他更详细地描述体内病理的文章，但请注意，由于不同的代谢宿主组织环境，细菌代谢可能会发生显著变化。例如，脓肿通常是缺氧和营养有限的；这可能会迫使细菌采取厌氧呼吸或发酵途径，降低对需氧摄取的氨基糖苷类药物敏感性。同样，在由大肠杆菌等病原体引起的尿路感染中，不同pH值的尿液中尿素和其他氮源的可用性可以促进代谢适应。这些变化对靶向叶酸合成途径的TMP-SMX等抗生素的疗效具有潜在影响。相比之下，囊性纤维化患者肺部富含黏蛋白的环境为铜绿假单胞菌提供独特碳源，诱发代谢转换并促进抗生素耐受。这些部位特异性代谢适应强调需结合病原体与宿主代谢状态设计治疗方案，因感染灶的代谢与空间异质性可显著改变药物效应。与这些发现一致，3500余株临床大肠埃希菌病原体的代谢基因突变谱揭示广阔的进化空间。全基因组CRISPR干扰筛选、转录组学与代谢组学联合分析表明，呼吸链、核糖体生物合成及核苷酸/氨基酸代谢通路构成异烟肼耐药结核分枝杆菌205菌株的药物脆弱性靶点。解析特定环境相关突变及其获益机制仍是活跃研究领域。除了当地宿主环境的代谢特征外，与驻留微生物群的相互作用还增加了另一层复杂性，因为这些微生物群落积极影响细菌行为、抗生素浓度和生物化学特性。例如，肠道微生物群起着至关重要的作用，如碳水化合物发酵、维生素合成、免疫调节和生物活性代谢物的产生。这些微生物活动直接影响药物代谢，改变抗生素的有效性和毒性。已知几种抗生素会被肠道微生物群共同代谢，包括甲硝唑和氯霉素。重要的是，个体之间肠道微生物群组成的变异性导致了对相同抗生素治疗的不同反应，突显了个性化医疗的主要挑战。例如，肠道中胆汁酸浓度的变化会改变环丙沙星和美罗培南对大肠杆菌的疗效，并促进铜绿假单胞菌生物膜的形成。因此，阐明体内代谢因素对抗生素治疗、应答及后续进化的影响，是开发适配个体代谢-微生物特征疗法的关键。 5 未来展望代谢深度参与细菌对抗生素应答的全过程，在开发新型抗生素及治疗策略时必须纳入考量。尽管代谢与抗生素治疗存在内在双向互作，当前研究主要聚焦抗生素对代谢的影响，而代谢如何调控药效、耐药演化及分子机制仍需系统阐释。深入解析复杂环境中的代谢网络将助力发现抗AMR新策略。生物膜中营养限制通过SOS/严谨反应增强耐受性，而营养补充可逆转此效应（小鼠模型已验证）；高密度环境下，葡萄糖刺激呼吸活动可克服大肠埃希菌、金黄色葡萄球菌及耻垢分枝杆菌对环丙沙星的密度依赖性耐受。在更大的相互作用网络和环境背景下更深入地了解这些关系，将有助于发现对抗AMR和/或最大限度地提高抗生素效用的新策略。就生物膜而言，对代谢作用的更深入理解提供了新的治疗前景。例如，研究表明，生物膜中的营养限制通过SOS或严格反应增加了对抗生素的耐受性。这些研究表明，通过营养补充促进代谢活动可能会限制耐受性和抗性，正如在小鼠模型中已经看到的那样。在历史上难以治疗的高密度环境下，葡萄糖刺激呼吸活动可克服大肠埃希菌、金黄色葡萄球菌及耻垢分枝杆菌对环丙沙星的密度依赖性耐受。采用新策略上调特定代谢通路是对抗抗生素耐药性和AMR的另一种有前景的方法。例如，利用氨基酸、TCA循环中间体和核苷酸等代谢产物可以恢复抗生素的致死性。其他药物也可能被设计为模拟抗生素活性并上调细菌代谢。例如，正在探索各种纳米粒子结构产生活性氧物种和氧化应激的能力。除了用佐剂补充抗生素外，独立利用代谢也可以作为一种抗菌策略。例如，合成工程铁螯合剂已被用于降低铁的生物利用度，导致生长抑制。使用这种创新设计的化合物的初步结果对金黄色葡萄球菌和鲍曼不动杆菌等生物体产生了中等至有前景的抗菌活性。其他利用铁代谢的策略包括使用镓等竞争金属来限制铁的吸收。镓化合物已被证明对与囊性纤维化、肺炎、慢性阻塞性肺病和一般伤口愈合相关的多药耐药性和机会性病原体有效。有趣的是，这些发现已经在许多环境中观察到，包括体外模型、体内小鼠模型、临床分离株和人类临床试验。尽管人们仍然担心这些药物的毒性作用，但其中一些化合物和类似化合物正在临床开发中。代谢干预效果具有情境依赖性。AMR演化及逆转不仅取决于当前代谢状态，更受历史选择压力影响。耐药菌株仅在原始进化环境或相似条件下维持耐药表型，而改变营养源恢复原始代谢效率可使其复敏。这表明有效代谢疗法需高度菌株特异性。长远看，环境与系统发育特征将决定代谢策略的普适性。除了菌株特异性外，利用宿主代谢为个性化抗生素治疗提供了一个尚未开发的机会，有可能更精确地改善治疗结果。目前的体外抗生素敏感性测试往往无法完全符合体内临床有效性，这突显了治疗传染病的一刀切模式忽视了关键的宿主-病原体、药代动力学和药效学因素。由不同感染部位和人与人之间的差异引起的代谢特异性因素可能会进一步导致这些差异。然而，这些因素在临床实践中仍未得到充分探索。此外，特定的微生物组环境可以调节抗生素活性和病原体行为。事实上，研究强调，肠道微生物组可以作为一个库，用于识别针对独特代谢环境量身定制的新的病原体特异性疗法。例如，抗生素、细菌素和微霉素等微生物组衍生药物有望成为精确的抗菌药物。特别是细菌素，在临床前模型中取得了成功；他们治疗了246只小鼠的铜绿假单胞菌肺部感染和248只牛和哺乳期妇女的乳腺炎。弥合基础研究和个性化医疗之间的差距需要明确的研究，将宿主介导和微生物组介导的代谢效应与观察到的临床差异联系起来。代谢在细菌对抗生素的反应中的复杂作用仍然不完全清楚，部分原因是缺乏优化的工具，无法将代谢效应与生长特异性或药物特异性的代谢效应区分开来。因此，必须设计分离代谢效应的方法。例如，代谢在典型外排AMR机制中的作用应从代谢物特异性和药物特异性转运蛋白中提取出来。此外，未来的技术，包括模拟和信息方法，在揭示新陈代谢的生长无关效应方面将非常有用。这些方法通常比物理量化方法更可行，包括基于通量的分析和动态全基因组建模，以及粗粒度方法。至关重要的是，生态进化模型将评估新策略的潜在演化后果，依托全基因组测序、质谱与预测建模整合多维数据。对抗AMR本质上是复杂的，需要病原体-环境-临床背景的特异性方案。构建综合代谢框架可推动传染病个性化治疗。患者生化特征、感染部位微环境及局部因素共同塑造体内代谢限制。深化代谢-AMR互作研究对开发下一代疗法、对提升全球AMR应对能力具有核心价值。原文链接：https://doi.org/10.1038/s41579-025-01155-0 版权声明本文转载“微生态”，版权属于原作者所有，文章翻译和转载为学术传播。团队水平有限，翻译和转载难免有不恰当之处，请批评指正，多多包涵！往期精彩回顾： #多组学研究 #感染与免疫 #生物医药与生态环境研究 #科技资讯与学术诚信 #衰老研究Aging #人工智能与大数据点赞！分享！转发！

2026-02-06

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奥玛环素：四环素家族的“新生代”，如何破解耐药困局

一位72岁的肺炎患者，在先后使用多种抗生素后仍反复高热，呼吸衰竭无改善，直到换成奥玛环素，体温才恢复正常，顺利出院。四环素类抗生素问世于上世纪40年代，曾以其广谱抗菌活性成为临床重要武器。然而，随着细菌耐药性的发展，尤其是四环素外排泵和核糖体保护这两种主要耐药机制的出现，传统四环素的疗效大打折扣。 --- 01 四环素困局当细菌学会了“泵出”药物或“改造”药物作用的靶点，昔日有效的武器便逐渐失效。近几十年来，四环素类新药研发进展缓慢，例如替加环素虽能克服部分耐药，但仅限于静脉给药，且存在安全性顾虑，限制了其广泛应用。面对日益严峻的社区获得性感染，临床急需一种既能有效克服常见耐药、又能方便口服给药的广谱新药。奥玛环素的研发，正是为了回应这一挑战。 02 新药诞生奥玛环素是一种新型氨甲基环素类抗生素。它是在经典四环素药物米诺环素的结构基础上，对D环的第7和第9位进行化学修饰而成的半合成化合物。这种独特的结构设计，使其能够同时规避细菌的两种主要耐药机制：外排泵和核糖体保护，从而对许多已对传统四环素耐药的菌株恢复活性。基于此，奥玛环素于2018年在美国首次获批上市，随后在中国获批，目前已被纳入国家医保目录。 03 疗效验证奥玛环素目前主要获批用于两种成人感染：社区获得性细菌性肺炎和急性细菌性皮肤及皮肤结构感染。其疗效在多项大型国际III期临床试验中得到了验证。在治疗皮肤感染方面，关键的OASIS-2研究显示，每日一次口服奥玛环素与每日两次口服利奈唑胺疗效相当。早期临床反应率分别为88%和83%，治疗结束后评估的临床成功率分别为84%和81%，达到了非劣效性标准。在治疗肺炎方面，OPTIC和OPTIC-2研究的汇总数据分析表明，奥玛环素的总体临床成功率超过86%。尤其值得注意的是，奥玛环素对多种常见且可能耐药的病原体展现了良好活性，如肺炎链球菌、流感嗜血杆菌、肺炎支原体、嗜肺军团菌以及耐甲氧西林金黄色葡萄球菌等。以下是奥玛环素关键临床研究结果概览：皮肤感染研究 (OASIS-2) · 主要对比药物：利奈唑胺（口服） · FDA标准早期临床反应率：88% vs. 83% · EMA标准治疗后临床成功率：84% vs. 81% · 核心结论：每日一次口服奥玛环素疗效不劣于每日两次口服利奈唑胺。肺炎研究 (OPTIC/OPTIC-2 汇总) · 主要对比药物：莫西沙星 · 最常见病原体：肺炎支原体、嗜肺军团菌、肺炎链球菌等 · 总体临床成功率：>86% (对大多数病原体) · 核心结论：疗效与莫西沙星相当。 04 精准使用奥玛环素分为静脉注射剂和口服片剂两种剂型，方便进行“静脉-口服”序贯治疗，即病情稳定后可从静脉输液转为口服药，有助于患者提前出院或避免住院。为确保药物最佳吸收，口服给药有严格的空腹要求。需在禁食至少4小时后，用水送服，服药后2小时内除水外不进食任何东西，4小时内避免摄入乳制品、抗酸剂或复合维生素等含多价阳离子的产品。治疗社区获得性细菌性肺炎的用法 · 起始剂量（第1天）：静脉注射200mg（单次）或100mg（两次）；或口服300mg（两次）。 · 维持剂量（第2天起）：静脉注射100mg每日一次；或口服300mg每日一次。 · 总疗程：7至14天。治疗皮肤感染的用法 · 起始剂量（第1、2天）：口服450mg每日一次。 · 维持剂量（第3天起）：口服300mg每日一次。 · 总疗程：7至14天。奥玛环素的一个显著优势是，对于肝肾功能不全的患者，通常无需调整剂量。它在体内主要通过粪便排泄（约80%），仅少部分经肾脏清除。 05 特殊注意尽管奥玛环素在安全性方面整体良好，与老一代四环素相比有一定改进，但临床使用时仍需关注以下几类特殊问题。首先是四环素类药物共有的不良反应。最常见的是胃肠道反应，如恶心、呕吐。在牙齿发育期（怀孕后半期、婴儿期至8岁儿童）使用，可能导致牙齿永久性变色和牙釉质发育不全。像所有抗生素一样，使用期间可能发生艰难梭菌相关性腹泻，一旦出现腹泻需及时评估。在药物相互作用方面，奥玛环素本身代谢率低，相互作用较少。但需特别注意，含铝、钙、镁的抗酸剂、铁剂等会严重干扰其吸收，必须间隔服用。此外，虽然说明书基于同类药物原则，建议孕妇、哺乳期妇女及8岁以下儿童避免使用。但近年来关于多西环素（另一种四环素）的短期使用证据提示，在某些严重感染（如立克次体病）中，短期用于儿童可能是利大于弊的。这反映了临床指南在证据更新下的动态变化。 06 未来展望奥玛环素的临床价值不仅在于其广谱抗菌活性，更在于它为应对耐药菌感染提供了一个重要的新选择。特别是在以下两类情况下：其一，适用于耐药菌，如MRSA、耐药肺炎链球菌等引起的社区感染。其二，方便进行序贯治疗，使符合条件的患者能从静脉输液顺利转为口服药，从而缩短住院时间，降低医疗成本。随着更多真实世界研究数据的积累，临床医生对奥玛环素的认识将更加深入，其应用也可能会超越目前的获批适应症，为更多复杂感染患者带来获益。

临床3期上市批准临床结果放射疗法

2026-02-06

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抗菌化疗杂志81卷 1-2期

Journal of Antimicrobial Chemotherapy Volume 81, Issue 1抗菌化疗杂志81卷 1期 https://academic.oup.com/jac/issue 50th Anniversary Collection 50周年纪念合集 Review（综述） 1 Artificial intelligence for improving decision-making in bacterial infection management: a narrative review 人工智能在改善细菌感染治疗决策中的应用：一项叙述性综述 Anisia Talianu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf470, https://doi.org/10.1093/jac/dkaf470 Reviews（综述） 2 Evolving landscape of methicillin-resistant Staphylococcus pseudintermedius: the emergence of new epidemic waves across Europe, Asia and North America 耐甲氧西林中间型葡萄球菌的演变格局：欧洲、亚洲和北美洲新流行浪潮的出现 Lillian Rose Giarratana and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf340, https://doi.org/10.1093/jac/dkaf340 3 Azithromycin resistance in non-typhoidal Salmonella: a review 非伤寒沙门氏菌对阿奇霉素的耐药性：综述 Zhe Zhu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf341, https://doi.org/10.1093/jac/dkaf341 4 Antibiotic pharmacodynamics: from MIC to advanced metrics and their applications 抗生素药效动力学：从最低抑菌浓度到高级指标及其应用 Malin Andersson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf374, https://doi.org/10.1093/jac/dkaf374 5 Progress in the study of drug resistance mechanism of Bacillus cereus 蜡样芽孢杆菌耐药机制研究进展 Yuhang Zhang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf399, https://doi.org/10.1093/jac/dkaf399 6 The curious constraints on clofazimine 氯法齐明的奇特限制 Maple Goh and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf430, https://doi.org/10.1093/jac/dkaf430 7 Antiplasmid systems: a novel strategy to combat antibiotic resistance 抗质粒系统：对抗抗生素耐药性的新策略 Mohd Asim and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf472, https://doi.org/10.1093/jac/dkaf472 Systematic Review（系统综述） 8 Coccidioidomycosis in Europe: a systematic literature review of epidemiology, treatment and outcomes 欧洲球孢子菌病：流行病学、治疗和预后的系统文献综述 Priya Shastri and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf407, https://doi.org/10.1093/jac/dkaf407 9 Systematic review of antimicrobial pharmacokinetic/pharmacodynamic indices in murine thigh and hollow fibre dose fractionation studies analysed with a standard method 用标准方法分析小鼠大腿和空心纤维剂量分次研究中的抗菌药物药代动力学/药效动力学指数的系统综述 Najla Alabdulkarim and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf446, https://doi.org/10.1093/jac/dkaf446 Virtual Roundtable（虚拟圆桌会议） 10 Procalcitonin in the management of lower respiratory tract infection and sepsis 降钙素原在下呼吸道感染和败血症治疗中的应用 Ramy H Elshaboury and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf298, https://doi.org/10.1093/jac/dkaf298 Original Research（论著） 11 Model-based assessment of letermovir pharmacokinetics in allogeneic haematopoietic stem cell transplant recipients 来特莫韦在异基因造血干细胞移植受者中药代动力学的基于模型的评估 Chrisoula Tahtsidou and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf427, https://doi.org/10.1093/jac/dkaf427 12 In vitro exebacase (CF-301) activity against methicillin-susceptible or methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci strains isolated from patients with infective endocarditis 体外试验评估依拉环素（CF-301）对甲氧西林敏感或甲氧西林耐药金黄色葡萄球菌及凝固酶阴性葡萄球菌（从感染性心内膜炎患者中分离）的活性 María-Alexandra Cañas and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf435, https://doi.org/10.1093/jac/dkaf435 13 Evaluation of subcutaneous amoxicillin/clavulanic acid pharmacokinetics as an alternative to the intravenous route in older patients—the PhASAge Study 评估皮下注射阿莫西林/克拉维酸药代动力学作为老年患者静脉给药替代方案——PhASAge研究 Nicolas Grégoire and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf381, https://doi.org/10.1093/jac/dkaf381 14 Real-life use of isavuconazole in Spanish children and adolescents 西班牙儿童和青少年中艾沙康唑的实际使用情况 Natalia Mendoza-Palomar and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf394, https://doi.org/10.1093/jac/dkaf394 15 No pharmacovigilance signal of intracranial hypertension associated with glycylcyclines: a FAERS-based disproportionality analysis 基于FAERS数据库的不成比例性分析：未发现甘氨酰环素类与颅内高压相关的药物警戒信号 Slobodan M Jankovic and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf395, https://doi.org/10.1093/jac/dkaf395 16 Posaconazole enteral tube administration in adults: pharmacokinetic target attainment of oral suspension compared with crushed delayed-release tablet 成人经肠内营养管给予泊沙康唑：口服混悬液与碾碎的缓释片的药代动力学目标达成情况比较 Nirjan Bhattarai and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf396, https://doi.org/10.1093/jac/dkaf396 17 Characterizing CYP3A4-mediated drug interactions: a fixed-sequence pharmacokinetic Chinese study of posaconazole and ruxolitinib in haematological malignancies CYP3A4介导的药物相互作用特征：一项关于泊沙康唑和鲁索替尼在血液系统恶性肿瘤中的固定序列药代动力学中国研究 Beibei Liang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf398, https://doi.org/10.1093/jac/dkaf398 18 Differences in prescription for impetigo and cellulitis across years in three European countries 三个欧洲国家不同年份脓疱病和蜂窝织炎的处方差异 Thomas Bettuzzi and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf400, https://doi.org/10.1093/jac/dkaf400 19 β-Lactam concentrations monitored in the early phase of community-acquired sepsis in the intensive care unit 重症监护室社区获得性脓毒症早期阶段监测的β-内酰胺浓度 Karolina Liljedahl Prytz and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf401, https://doi.org/10.1093/jac/dkaf401 20 Enhanced antimycobacterial efficacy of simulated inhaled clofazimine versus oral clofazimine in combination with azithromycin and ethambutol in a hollow-fiber system 在空心纤维系统中，模拟吸入氯法齐明与口服氯法齐明联合阿奇霉素和乙胺丁醇的抗结核分枝杆菌疗效增强比较 Jelmer Raaijmakers and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf402, https://doi.org/10.1093/jac/dkaf402 21 Identification of antimicrobial resistance genes in Escherichia coli through network diffusion 通过网络扩散法鉴定大肠杆菌中的抗生素耐药基因 Anis Mansouri and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf404, https://doi.org/10.1093/jac/dkaf404 22 Preclinical evaluation of epetraborole in the hollow fibre system model of Mycobacterium abscessus lung disease 依培硼罗在脓肿分枝杆菌肺病空心纤维系统模型中的临床前评估 Sanjay Singh and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf405, https://doi.org/10.1093/jac/dkaf405 23 The β-lactamase inhibitor concentration-dependent minimum inhibitory concentration (MICcBLI) as methodology to assess the pharmacokinetic/pharmacodynamic relationship of piperacillin/tazobactam for dosing optimization β-内酰胺酶抑制剂浓度依赖性最低抑菌浓度（MICcBLI）作为评估哌拉西林/他唑巴坦药代动力学/药效动力学关系以优化给药的方法 Malin Andersson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf406, https://doi.org/10.1093/jac/dkaf406 24 Unravelling the triad of penicillin-binding proteins, β-lactamase activity, and mRNA dynamics in Pseudomonas aeruginosa AmpC induction 解析铜绿假单胞菌AmpC诱导过程中青霉素结合蛋白、β-内酰胺酶活性和mRNA动态的三元关系 Maria Montaner and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf408, https://doi.org/10.1093/jac/dkaf408 25 Unnoticed spread of linear VanA-plasmids in vancomycin-variable Enterococcus faecium strains across different regions: a diagnostics challenge 不同地区万古霉素可变型粪肠球菌菌株中线性VanA质粒的未被察觉的传播：一项诊断挑战 Ana C Almeida-Santos and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf409, https://doi.org/10.1093/jac/dkaf409 26 Switching from etravirine to doravirine in virologically suppressed people with HIV: results from the French multicentre SWEED observational study 在病毒学抑制的HIV感染者中从依曲韦林切换至多拉韦林：法国多中心SWEED观察性研究的结果 Romain Palich and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf410, https://doi.org/10.1093/jac/dkaf410 27 HIV-1 drug resistance among pregnant and breastfeeding mothers and its association with paediatric HIV infections in the Dolutegravir era in Uganda 乌干达多替拉韦时代孕产妇及哺乳期母亲中HIV-1耐药情况及其与儿童HIV感染的关联 Anne Kapaata and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf411, https://doi.org/10.1093/jac/dkaf411 28 Outpatient antibiotic prescribing for medically attended respiratory syncytial virus, influenza, or human metapneumovirus illness among high-risk adults in rural Wisconsin, United States 美国威斯康星州农村地区高风险成人因呼吸道合胞病毒、流感或人偏肺病毒感染就诊时的门诊抗生素处方情况 Sarah C J Jorgensen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf412, https://doi.org/10.1093/jac/dkaf412 29 Omadacycline as a drug candidate for Mycobacterium avium infections: in vitro insights on single and combination therapies 奥马环素作为鸟分枝杆菌感染候选药物：单药及联合治疗的体外研究 Saskia E Mudde and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf413, https://doi.org/10.1093/jac/dkaf413 30 Post-pandemic trends in Streptococcus pneumoniae serotype epidemiology and antibiotic susceptibility in adults with invasive and non-invasive pneumococcal disease in the USA (2022–2023) 后疫情时代美国成人侵袭性与非侵袭性肺炎链球菌病血清型流行病学及抗生素敏感性趋势（2022-2023） Mekki F Bensaci and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf414, https://doi.org/10.1093/jac/dkaf414 31 Benznidazole pharmacokinetics in patients with chronic Chagas disease: association with demographic factors and adverse drug reactions 慢性恰加斯病患者苯芴醇药代动力学：与人口统计学因素及药物不良反应的关联 Gabriel P E Silveira and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf416, https://doi.org/10.1093/jac/dkaf416 32 Acquired antimicrobial resistance genes in Bordetella Species: a global genomic analysis 博德特氏菌属中获得的抗菌药物耐药基因：全球基因组分析 Biao Tang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf418, https://doi.org/10.1093/jac/dkaf418 33 Machine learning for personalized antimicrobial susceptibility breakpoints: (Adaptive clinical breakpoint interpretation) 基于机器学习的个性化抗菌药物敏感性折点制定（自适应临床折点解释） Yinzheng Zhong and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf419, https://doi.org/10.1093/jac/dkaf419 34 Multicentre investigation of Wickerhamomyces anomalus fungemia in India: emerging resistance and mechanistic insights 印度异常威克汉姆酵母菌血症的多中心研究：新发耐药性及机制洞察 Shristi Verma and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf420, https://doi.org/10.1093/jac/dkaf420 35 Reducing aztreonam/avibactam waste: insights from Monte Carlo simulations 减少氨曲南/阿维巴坦浪费：蒙特卡洛模拟的启示 Yeleen Fromage and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf421, https://doi.org/10.1093/jac/dkaf421 36 Nanoparticle-based co-delivery of ciprofloxacin and meropenem enhances synergistic activity against multidrug-resistant hypervirulent Klebsiella pneumoniae clinical isolates 基于纳米颗粒的环丙沙星与美罗培南共递送可增强对多重耐药高毒力肺炎克雷伯菌临床分离株的协同活性 Reham Mostafa and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf422, https://doi.org/10.1093/jac/dkaf422 37 Development of population pharmacokinetic models of total and free piperacillin in critically ill children and young adults for Monte Carlo simulations and model-informed precision dosing 危重症儿童及青年总游离哌拉西林群体药代动力学模型开发：用于蒙特卡洛模拟及模型引导的精准给药 Sonya Tang Girdwood and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf423, https://doi.org/10.1093/jac/dkaf423 38 Reaching the target: time and dose required to achieve target vancomycin plasma concentrations in admitted patients 达标分析：住院患者达到目标万古霉素血浆浓度所需的时间与剂量 W Töpfer and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf424, https://doi.org/10.1093/jac/dkaf424 39 Notable transmitted HIV drug resistance among people who inject drugs in Pakistan 巴基斯坦注射毒品人群中显著传播的HIV耐药性 Stephanie Melnychuk and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf425, https://doi.org/10.1093/jac/dkaf425 40 Synergistic but clinically unattainable: amoxicillin/ceftriaxone combination against ampicillin-susceptible Enterococcus faecium 协同但临床难以实现：阿莫西林/头孢曲松联合对氨苄西林敏感粪肠球菌的体外活性 Ahmed Ashrin and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf426, https://doi.org/10.1093/jac/dkaf426 41 Pharmacodynamic studies of taniborbactam (VNRX-5133) combined with cefepime against β-lactamase–producing Gram-negative bacteria in a neutropenic murine thigh infection model 中性粒细胞减少小鼠大腿感染模型中他尼硼巴坦（VNRX-5133）联合头孢吡肟对产β-内酰胺酶革兰氏阴性菌的药效动力学研究 Panagiota-Christina Georgiou and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf431, https://doi.org/10.1093/jac/dkaf431 42 Epidemiology and treatment of endocarditis secondary to Enterobacterales other than Serratia spp. 非塞拉蒂亚属肠杆菌目细菌所致心内膜炎的流行病学及治疗 Clayton F Hausberger and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf432, https://doi.org/10.1093/jac/dkaf432 43 Enhanced activity of apramycin and apramycin-based combinations against Mycobacteroides abscessus 阿普拉霉素及其组合对脓肿分枝杆菌的增强活性 Yanqin Huang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf433, https://doi.org/10.1093/jac/dkaf433 44 Efflux-mediated multidrug resistance mechanism in Trichophyton indotineae and Trichophyton rubrum; role of ABC transporters and MFS gene 印度毛癣菌与红色毛癣菌中由ABC转运蛋白和MFS基因介导的流出泵型多重耐药机制 Dipika Shaw and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf434, https://doi.org/10.1093/jac/dkaf434 45 Sphingobacterium spp. as intrinsic producers of SPI Ambler class B metallo-β-lactamases 鞘氨醇杆菌属作为SPI Ambler B类金属β-内酰胺酶的固有产生者 Delphine Girlich and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf436, https://doi.org/10.1093/jac/dkaf436 46 Global phylogeography and genomic characterization of blaNDM-1-positive carbapenem-resistant Acinetobacter soli blaNDM-1阳性碳青霉烯耐药溶胶阿卡净菌的全球系统发育地理学及基因组特征 Pengpeng Min and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf437, https://doi.org/10.1093/jac/dkaf437 47 Pharmacokinetics and tolerability of one-month daily rifapentine for latent tuberculosis treatment in haemodialysis patients 血液透析患者潜伏性结核治疗中每月一次每日利福喷丁的药代动力学及耐受性 Thornthun Ueaphongsukkit and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf439, https://doi.org/10.1093/jac/dkaf439 48 In vitro susceptibility of cefepime-enmetazobactam, cefepime-taniborbactam and cefepime-zidebactam towards carbapenemase-producing Enterobacterales 头孢吡肟-恩美他唑巴坦、头孢吡肟-他尼硼巴坦及头孢吡肟-齐德巴坦对产碳青霉烯酶肠杆菌目的体外敏感性 Marion Dutkiewicz and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf440, https://doi.org/10.1093/jac/dkaf440 49 In vitro efficacy of sulbactam/durlobactam combined with β-lactam antibiotics in Australian Mycobacterium abscessus isolates 舒巴坦/杜洛巴坦联合β-内酰胺类抗生素对澳大利亚脓肿分枝杆菌分离株的体外疗效 Kirby Patterson-Fahy and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf441, https://doi.org/10.1093/jac/dkaf441 50 Harnessing CRISPR–Cas9 and CRISPRi systems to reverse antibiotic resistance in a clinical multidrug-resistant Escherichia coli isolate 利用CRISPR-Cas9及CRISPRi系统逆转临床多重耐药大肠杆菌分离株的抗生素耐药性 Ruonan Zhao and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf442, https://doi.org/10.1093/jac/dkaf442 51 Cotrimoxazole in the intensive care unit: an impossible task for the fixed association in real life? 重症监护室中复方磺胺甲噁唑的应用：固定组合在现实中的不可行性？ Manon Launay and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf443, https://doi.org/10.1093/jac/dkaf443 52 National representative survey of pretreatment HIV drug resistance in Colombia: analysis of antiretroviral resistance-associated mutations using next-generation sequencing 哥伦比亚全国代表性调查：基于下一代测序的抗逆转录病毒耐药相关突变分析 Ernesto Martínez-Buitrago and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf444, https://doi.org/10.1093/jac/dkaf444 53 A model-based comparison of dose reduction strategies for fixed-dose dolutegravir-containing regimens 基于模型的含固定剂量多替拉韦方案减量策略比较 Laura Dickinson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf445, https://doi.org/10.1093/jac/dkaf445 54 Therapeutic drug monitoring and target attainment of unbound flucloxacillin in hospitalized patients with measured MICs (FLUTE) 住院患者中游离氟氯西林的治疗药物监测及目标达成情况（基于实测最低抑菌浓度的FLUTE研究） Pjotr P Temme and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf447, https://doi.org/10.1093/jac/dkaf447 55 Nirmatrelvir-ritonavir addition to acute care formulary: a retrospective, multi-centre evaluation of quantitative economic and qualitative clinical outcomes 奈玛特韦/利托那韦纳入急症治疗目录：一项多中心回顾性评估定量经济与定性临床结果的研究 Jose Valdes Ledesma and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf448, https://doi.org/10.1093/jac/dkaf448 56 Local antibiotic resistance surveillance in nursing homes using lot quality assurance sampling: a feasibility study 采用批量质量保证抽样法对养老院进行本地抗生素耐药性监测的可行性研究 Sacha Kuil and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf451, https://doi.org/10.1093/jac/dkaf451 57 High in vitro activity of the novel antimicrobial gepotidacin against Neisseria gonorrhoeae isolates in eight WHO Enhanced Gonococcal Antimicrobial Surveillance Programme countries in three WHO regions, 2021–24 2021-2024年，在世卫组织三个区域的八个世卫组织增强淋球菌抗菌药物监测计划国家中，新型抗菌药物吉皮达星对淋病奈瑟菌分离株的体外活性较高 Josefine Ahlstrand and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf452, https://doi.org/10.1093/jac/dkaf452 58 Despite increasing use of integrase inhibitors to treat HIV infection, resistance to this class remains stable 尽管整合酶抑制剂用于治疗HIV感染的使用量不断增加，但此类药物的耐药性仍保持稳定 Cathia Soulie and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf454, https://doi.org/10.1093/jac/dkaf454 59 Fine-needle aspiration in infected necrotizing pancreatitis in the delayed intervention era: a post hoc analysis of safety, microbiological yield and therapeutic implications 延迟干预时代感染性坏死性胰腺炎的细针穿刺抽吸术：安全性、微生物学检出率及治疗意义的事后分析 Hannah S Pauw and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf455, https://doi.org/10.1093/jac/dkaf455 60 β-Lactam dosing in critically ill children: predictors for target non-attainment 危重症儿童β-内酰胺类药物给药：未达目标浓度的预测因素 Stef Schouwenburg and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf457, https://doi.org/10.1093/jac/dkaf457 61 Co-administration of triazoles with calcineurin or mammalian target of rapamycin inhibitors in solid organ transplant patients hospitalized with invasive aspergillosis 实体器官移植患者合并侵袭性曲霉病住院时三唑类药物与钙调磷酸酶抑制剂或哺乳动物雷帕霉素靶蛋白抑制剂的联合用药情况 Barbara Alexander and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf461, https://doi.org/10.1093/jac/dkaf461 62 In vitro selection of cefiderocol-resistant mutants in Acinetobacter baumannii harbouring the most common carbapenemase genes 携带最常见碳青霉烯酶基因的鲍曼不动杆菌中头孢地尔耐药突变体的体外筛选 Otávio Hallal Ferreira Raro and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf462, https://doi.org/10.1093/jac/dkaf462 63 Preventing resistance development in infections by OXA β-lactamase-producing Pseudomonas aeruginosa: correlating clinical outcomes with hollow-fibre model input 预防产OXA β-内酰胺酶铜绿假单胞菌感染耐药性的产生：将临床结局与中空纤维模型输入相关联 María M Montero and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf464, https://doi.org/10.1093/jac/dkaf464 64 A national pilot community pharmacy–led urinary tract infection service: clinical and patient-reported outcomes from 9077 consultations 全国社区药房主导的尿路感染服务试点项目：9077次咨询的临床结局和患者报告结局 Efi Mantzourani and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf466, https://doi.org/10.1093/jac/dkaf466 65 Towards enhanced translational value: preclinical drug activity testing against actively multiplying, nutrient-starved and pellicle biofilm-embedded Mycobacterium abscessus 提高转化价值：针对活跃增殖、营养匮乏和生物膜包裹的脓肿分枝杆菌进行临床前药物活性测试 Henriëtte M Meliefste and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf468, https://doi.org/10.1093/jac/dkaf468 Research Letters（研究快报） 66 Novel multiresistance transposon Tn7731 in bovine Pasteurella multocida from Germany 德国牛源多杀性巴氏杆菌中新型多重耐药转座子Tn7731 Henrike Krüger-Haker and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf336, https://doi.org/10.1093/jac/dkaf336 67 Efficacy of eravacycline in difficult-to-treat (DTR) Acinetobacter baumannii bacteraemia in ICU: a case report 厄他培南治疗重症监护病房难治性鲍曼不动杆菌菌血症的疗效：一例病例报告 Monica Melchio and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf347, https://doi.org/10.1093/jac/dkaf347 68 Possible increased risk of Epstein–Barr virus (EBV) infection and post-transplant lymphoproliferative disease (PTLD) in letermovir-exposed haematopoietic cell transplantation recipients 来特莫韦暴露的造血细胞移植受者中EB病毒感染和移植后淋巴增殖性疾病风险可能增加 Jose F Camargo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf348, https://doi.org/10.1093/jac/dkaf348 69 Dalbavancin dosing in a severely underweight woman with prosthetic valve endocarditis: the critical role of proactive therapeutic drug monitoring 达巴万星在严重体重不足人工瓣膜心内膜炎女性患者中的给药：主动治疗药物监测的关键作用 Ambra Barco and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf365, https://doi.org/10.1093/jac/dkaf365 70 Cefazolin-induced seizures in a haemodialysis patient with elevated serum and cerebrospinal fluid concentrations: a case report 血液透析患者头孢唑林血清和脑脊液浓度升高诱发癫痫：一例病例报告 Kohei Hasegawa and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf373, https://doi.org/10.1093/jac/dkaf373 71 Retrospective analysis of pharmacological therapeutic monitoring of caspofungin in patients undergoing continuous renal replacement therapy using polyacrylonitrile membranes 使用聚丙烯腈膜进行连续性肾脏替代治疗的患者中卡泊芬净药代动力学治疗监测的回顾性分析 Antoine Hérault and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf390, https://doi.org/10.1093/jac/dkaf390 72 Diffusion of OXA-48- and NDM-5-producing Klebsiella pneumoniae ST383 clone in Central Italy 产OXA-48和NDM-5的肺炎克雷伯菌ST383克隆在意大利中部的传播 Gloria D’Achille and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf397, https://doi.org/10.1093/jac/dkaf397 73 Durability of lenacapavir in viremic heavily treatment-experienced people with HIV: real-world data from the PRESTIGIO Registry 来那卡帕韦在病毒载量阳性且接受过大量抗逆转录病毒治疗的HIV感染者中的持久性：来自PRESTIGIO登记处的现实数据 Tommaso Clemente and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf415, https://doi.org/10.1093/jac/dkaf415 74 Co-carriage of the oxazolidinone resistance genes cfr and optrA in a linezolid-resistant Staphylococcus rostri isolate from a pig-farm worker 猪场工人利奈唑胺耐药猪鼻支原体分离株中噁唑烷酮类耐药基因cfr和optrA的共携带情况 Gi Yong Lee and Soo-Jin Yang Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf428, https://doi.org/10.1093/jac/dkaf428 75 Importance of reviewing the package insert from gradient strip manufacturers 梯度扩散法药敏纸片生产商说明书审阅的重要性 Mandy Wootton and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf429, https://doi.org/10.1093/jac/dkaf429 76 One resistance gene, many transposons: repeated formation of compound and pseudo-compound transposons carrying the aphA1 kanamycin and neomycin resistance gene 一个耐药基因，多个转座子：携带aphA1卡那霉素和新霉素耐药基因的复合及假复合转座子的重复形成 Christopher J Harmer and Ruth M Hall Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf450, https://doi.org/10.1093/jac/dkaf450 77 Absence of lymphogranuloma venereum among men who have sex with men on PrEP receiving doxycycline postexposure prophylaxis 接受暴露后多西环素预防性治疗的暴露前预防用药男男性行为者中未发现性病淋巴肉芽肿 Cristina Gómez-Ayerbe and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf456, https://doi.org/10.1093/jac/dkaf456 78 In vitro activity of gepotidacin against Chlamydia trachomatis 吉皮达星对沙眼衣原体的体外活性 Arabella Touati and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf460, https://doi.org/10.1093/jac/dkaf460 Journal of Antimicrobial Chemotherapy Volume 81, Issue 2抗菌化疗杂志 81卷 2期 https://academic.oup.com/jac/issue Viewpoints（观点） 1 Long-acting glycopeptides: what are the barriers to access in patients who need them most, and how can they be overcome? 长效糖肽类：最需要它们的患者获取药物的障碍有哪些，如何克服？ Aleece MacPhail and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf471, https://doi.org/10.1093/jac/dkaf471 2 Redefining antifungal prophylaxis in acute leukaemia in the era of targeted therapies 靶向治疗时代急性白血病抗真菌预防的重新定义 Marcio Nucci and Johan Maertens Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag010, https://doi.org/10.1093/jac/dkag010 Reviews（综述） 3 Research progress on resistance mechanisms and clinical efficacy of tigecycline against Klebsiella pneumoniae 替加环素对肺炎克雷伯菌的耐药机制及临床疗效研究进展 Meilin Wu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf504, https://doi.org/10.1093/jac/dkaf504 4 Liposomal amphotericin B and renal safety: review of the evidence and clinical considerations 两性霉素B脂质体与肾脏安全性：证据回顾及临床考量 Johan Maertens and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf473, https://doi.org/10.1093/jac/dkaf473 5 Strategies for mitigating severe COVID-19 in patients with haematological malignancy during the omicron era 奥密克戎时代减轻血液系统恶性肿瘤患者严重新冠肺炎的策略 Keiji Okinaka and Joshua T Schiffer Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf489, https://doi.org/10.1093/jac/dkaf489 Systematic Reviews（系统综述） 6 Safety and efficacy of gepotidacin in urinary tract infection: a GRADE-assessed systematic review and meta-analysis 吉泊替达辛治疗尿路感染的安全性和有效性：一项基于GRADE评估的系统综述和荟萃分析 Taha Ibrahim and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf469, https://doi.org/10.1093/jac/dkaf469 7 The emerging clinical relevance and antimicrobial resistance of Pluralibacter gergoviae: a systematic review 产吲哚金黄杆菌日益凸显的临床相关性和抗菌药物耐药性：一项系统综述 Bruna Abdul Ahad Saad and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf476, https://doi.org/10.1093/jac/dkaf476 8 A comprehensive analysis of the mutational landscape determining polymyxin resistance in Klebsiella pneumoniae 决定肺炎克雷伯菌多粘菌素耐药性的突变谱综合分析 Sambit Kumar Dwibedy and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf503, https://doi.org/10.1093/jac/dkaf503 9 Factors promoting or hindering self-administered outpatient parenteral antimicrobial therapy: a systematic literature review 促进或阻碍自我给药门诊静脉注射抗菌药物治疗的因素：一项系统文献综述 Hester H Stoorvogel and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf490, https://doi.org/10.1093/jac/dkaf490 Original Research（论著） 10 Cefepime/enmetazobactam for Gram-negative periprosthetic joint infections? A randomized porcine study on target tissue pharmacokinetics 头孢吡肟/恩美唑巴坦治疗革兰氏阴性假体周围关节感染？一项关于猪的靶组织药代动力学的随机研究 M B D Nielsen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf487, https://doi.org/10.1093/jac/dkaf487 11 Impact of extracorporeal membrane oxygenation modes on voriconazole exposure in critically ill patients 体外膜肺氧合模式对危重患者伏立康唑暴露的影响 Xinrui Wang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf501, https://doi.org/10.1093/jac/dkaf501 12 Model-based assessment of VRC07-523LS dosing in infants through population pharmacokinetic -pharmacodynamic modelling in adults and infants 基于模型通过成人和婴儿群体药代动力学-药效学模型评估VRC07-523LS在婴儿中的给药方案 Dustin Huynh and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf449, https://doi.org/10.1093/jac/dkaf449 13 Antibiotic resistance of Pseudomonas aeruginosa strains—intracellular metabolomics analysis 铜绿假单胞菌菌株的抗生素耐药性——细胞内代谢组学分析 Karolina Anna Mielko-Niziałek and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf453, https://doi.org/10.1093/jac/dkaf453 14 In vitro activity of cefepime/zidebactam against sulbactam/durlobactam-susceptible and -resistant Acinetobacter baumannii clinical isolates 头孢吡肟/齐多巴坦对舒巴坦/杜洛巴坦敏感和耐药鲍曼不动杆菌临床分离株的体外活性 Carlo Tascini and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf467, https://doi.org/10.1093/jac/dkaf467 15 Prevalence of macrolide resistance in Mycoplasma pneumoniae in The Netherlands 荷兰肺炎支原体大环内酯类抗生素耐药性的流行情况 Patrick D J Sturm and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf475, https://doi.org/10.1093/jac/dkaf475 16 Simulated lung exposure in pneumonia patients to evaluate the antibacterial capacity and resistance suppression of clinical tigecycline regimens against carbapenem-resistant Acinetobacter baumannii 模拟肺炎患者肺部暴露情况以评估临床替加环素方案对碳青霉烯类耐药鲍曼不动杆菌的抗菌能力和耐药抑制作用 Xiaonan Zhang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf477, https://doi.org/10.1093/jac/dkaf477 17 Enterococcus faecium harbouring vanA, optrA and cfr(D) on a linear plasmid in Canada: a CANWARD surveillance case 加拿大发现携带vanA、optrA和cfr(D)的粪肠球菌线性质粒：一项CANWARD监测病例 Melissa McCracken and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf478, https://doi.org/10.1093/jac/dkaf478 18 The effect of intrauterine exposure to aminoglycosides on neonatal hearing 宫内暴露于氨基糖苷类抗生素对新生儿听力的影响 Daniel Leshin-Carmel and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf483, https://doi.org/10.1093/jac/dkaf483 19 Ceftazidime/avibactam: a potent arsenal against multidrug-resistant Pseudomonas aeruginosa-unveiling in vitro and in vivo strategies 头孢他啶/阿维巴坦：对抗多重耐药铜绿假单胞菌的有力武器——揭示体内外策略 Jiaju Zhuo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf495, https://doi.org/10.1093/jac/dkaf495 20 Comparison of disk diffusion, MIC test strip and broth microdilution for eravacycline susceptibility testing of 422 Staphylococcus aureus isolates using ChinaCAST breakpoints 采用中国CAST折点，比较422株金黄色葡萄球菌对依拉环素的纸片扩散法、最低抑菌浓度测试条法和肉汤微量稀释法的敏感性测试结果 Xinying Wang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf502, https://doi.org/10.1093/jac/dkaf502 21 Penetration of daptomycin in cerebrospinal fluid during pneumococcal meningitis 肺炎链球菌性脑膜炎期间达托霉素在脑脊液中的渗透情况 Pascal Chavanet and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf474, https://doi.org/10.1093/jac/dkaf474 22 Rapid molecular diagnostics for detection of extensively drug-resistant Salmonella Typhi 用于检测广泛耐药伤寒沙门菌的快速分子诊断技术 Emma L Sweeney and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf481, https://doi.org/10.1093/jac/dkaf481 23 Gender inequality and antibiotic consumption: analysis of pharmaceutical sales data from 70 countries, 2000–22 性别不平等与抗生素消费：基于2000 - 2022年70个国家药品销售数据的分析 Deepshikha Batheja and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag002, https://doi.org/10.1093/jac/dkag002 24 Real-world evaluation of isavuconazole in children with cancer 伊沙康唑在儿童癌症患者中的现实应用评估 Janine Nijhuis and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf485, https://doi.org/10.1093/jac/dkaf485 25 Assessing antimicrobial susceptibility testing guideline adherence by laboratories providing bacteriology services in Ghana: a pilot study 加纳提供细菌学服务的实验室对抗菌药物敏感性试验指南依从性的评估：一项试点研究 Joseph Elikem Efui Acolatse and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag003, https://doi.org/10.1093/jac/dkag003 26 Resistance to second-generation integrase inhibitors in people with HIV following treatment failure on dolutegravir- or bictegravir-based ART in Taiwan 台湾地区基于多替拉韦或比克替拉韦的抗逆转录病毒治疗失败后，HIV感染者对第二代整合酶抑制剂的耐药性 Guan-Jhou Chen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf488, https://doi.org/10.1093/jac/dkaf488 27 In vitro activity of gepotidacin against a challenging panel of multidrug-resistant Neisseria gonorrhoeae isolates 吉泊西汀对一组具有挑战性的多重耐药淋病奈瑟菌分离株的体外活性 Michelle Jayne Cole and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag001, https://doi.org/10.1093/jac/dkag001 28 A disproportionality analysis of adverse events associated with omadacycline based on the FDA adverse event reporting system database 基于美国食品药品监督管理局（FDA）不良事件报告系统数据库的奥马环素相关不良事件比例失衡分析 Ye-Lei Zhao and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag006, https://doi.org/10.1093/jac/dkag006 29 Weight-band-based simplification of oral allometric miltefosine dosing in paediatric patients with visceral leishmaniasis 基于体重范围的口服异速缩放米替福新给药方案在儿童内脏利什曼病患者中的简化应用 Andres Mazariegos Herrera and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag014, https://doi.org/10.1093/jac/dkag014 30 evelopment of a capability framework for antimicrobial stewardship specialist health professionals working in the NHS in England: utilizing Delphi methodology 运用德尔菲法为在英国国家医疗服务体系（NHS）中工作的抗菌药物管理专业人员制定能力框架 Ryan A Hamilton and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf438, https://doi.org/10.1093/jac/dkaf438 31 First characterization of insertions in the HIV-1 integrase-coding region from people with HIV 首次对来自艾滋病病毒感染者的HIV-1整合酶编码区插入情况进行特征分析 Nhat Quang Tu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf491, https://doi.org/10.1093/jac/dkaf491 32 Development of an impedance-based fast antimicrobial susceptibility test for Neisseria gonorrhoeae 开发一种基于阻抗的淋病奈瑟菌快速抗菌药物敏感性检测方法 Caitlin N Daniels and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf493, https://doi.org/10.1093/jac/dkaf493 33 Juvenile toxicity and developmental safety of Zintrodiazine, a novel antimalarial candidate, in Wistar rats 新型抗疟候选药物Zintrodiazine在Wistar大鼠中的幼年毒性和发育安全性研究 Hitesh A Kadu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag008, https://doi.org/10.1093/jac/dkag008 34 Do the redefined EUCAST susceptibility categories warrant adjustment of paediatric antibiotic dosages? Pragmatic physiologically based pharmacokinetic modelling of four commonly used agents 欧洲抗微生物药物敏感性试验委员会（EUCAST）重新定义的敏感性分类是否需要调整儿童抗生素剂量？——对四种常用药物的实用生理药代动力学建模研究 Marika A de Hoop-Sommen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf463, https://doi.org/10.1093/jac/dkaf463 35 Exploring the opportunity for therapeutic drug monitoring (TDM) and precision dose antimicrobials in an outpatient antimicrobial therapy (OPAT) service: a prospective observational study 门诊抗菌治疗（OPAT）服务中开展治疗药物监测（TDM）和精准剂量抗菌治疗的机遇：一项前瞻性观察研究 R C Wilson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf484, https://doi.org/10.1093/jac/dkaf484 36 Impact of sex, age and body composition on rilpivirine and cabotegravir trough concentrations in people with HIV receiving long-acting injectable antiretroviral therapy 性别、年龄和身体成分对接受长效注射用抗逆转录病毒治疗的HIV感染者利匹韦林和卡博特韦谷浓度的影响 Maria Vittoria Cossu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag024, https://doi.org/10.1093/jac/dkag024 37 Pharmacokinetics of cefiderocol during prolonged intermittent kidney replacement therapy in two patients with septic shock 头孢地尔在两例感染性休克患者长时间间歇性肾脏替代治疗期间的药代动力学 Julius J Schmidt and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf496, https://doi.org/10.1093/jac/dkaf496 38 Understanding mechanisms of reduced cefiderocol susceptibility in pvdS and fecI mutants of Pseudomonas aeruginosa 了解铜绿假单胞菌pvdS和fecI突变体对头孢地尔敏感性降低的机制 Yoshinori Yamano and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag004, https://doi.org/10.1093/jac/dkag004 39 Biomarker-informed PBPK modelling of meropenem in paediatric severe pneumonia: implications for target-site PK/PD 基于生物标志物的美罗培南在儿童重症肺炎中的生理药动学模型构建：对靶部位药代动力学/药效学的影响 Yao Liu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf500, https://doi.org/10.1093/jac/dkaf500 40 Evaluating hypoalbuminaemia thresholds associated with delayed blood sterilization among patients receiving cefazolin or antistaphylococcal penicillins for MSSA bacteraemia 评估接受头孢唑林或抗葡萄球菌青霉素治疗甲氧西林敏感金黄色葡萄球菌（MSSA）菌血症患者中，与血液延迟灭菌相关的低白蛋白血症阈值 Sunish Shah and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf498, https://doi.org/10.1093/jac/dkaf498 Research Letters（研究快讯） 41 False-negative result in fourth-generation HIV screening tests after weak detection of p24 antigen in the context of inappropriate post-exposure prophylaxis use: a case report 不当使用暴露后预防用药导致第四代HIV筛查试验p24抗原弱检出后出现假阴性结果：一例病例报告 J Kimmerlin and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf459, https://doi.org/10.1093/jac/dkaf459 42 Proposal for the nomenclature of tmexCD-toprJ-like gene clusters 关于tmexCD-toprJ样基因簇命名的建议 Chengzhen Wang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf482, https://doi.org/10.1093/jac/dkaf482 43 IS26-mediated chromosomal integration of virulence plasmid fragments in ST2237 carbapenem-resistant Klebsiella pneumoniae IS26介导的毒力质粒片段在ST2237型碳青霉烯耐药肺炎克雷伯菌染色体中的整合 Yan Li and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag018, https://doi.org/10.1093/jac/dkag018 Letter to the Editor（致编辑的信） 44 Comment on: Retrospective analysis of pharmacological therapeutic monitoring of caspofungin in patients undergoing continuous renal replacement therapy using polyacrylonitrile membranes 对“采用聚丙烯腈膜对接受连续性肾脏替代治疗的患者进行卡泊芬净药代动力学监测的回顾性分析”的评论 Gwénola Marais and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf465, https://doi.org/10.1093/jac/dkaf465 45 Antimicrobial use for the treatment of bacterial sexually transmitted infections among doxycycline post-exposure prophylaxis (DoxyPEP) users in Milan, Italy-right-to-reply 意大利米兰地区使用多西环素暴露后预防（DoxyPEP）人群中，用于治疗细菌性传播感染的抗菌药物使用情况——回应说明 Angelo Roberto Raccagni and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag027, https://doi.org/10.1093/jac/dkag027 ACKNOWLEDGEMENT OF REFEREES（鸣谢审稿专家） 46 Acknowledgement of Referees 鸣谢审稿专家 Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf417, https://doi.org/10.1093/jac/dkaf417 CORRECTION（更正） 47 Correction to: Comment on: Antiviral effect of Evusheld in COVID-19 hospitalized patients infected with pre-Omicron or Omicron variants: a modelling analysis of the randomized DisCoVeRy trial 更正：关于Evusheld在感染奥密克戎变异株前或奥密克戎变异株的新冠住院患者中的抗病毒效果：对随机DisCoVeRy试验的建模分析的评论 Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf492, https://doi.org/10.1093/jac/dkaf492

临床结果临床1期

100 项与利奈唑胺相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00947	利奈唑胺	J01XX08	DB00601

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
皮肤和皮肤结构感染	美国	Hospira, Inc.	2015-06-18
菌血症	中国	Pfizer Inc.	2006-09-12
细菌感染	中国	Pfizer Inc.	2006-09-12
复杂的皮肤和软组织感染	中国	Pfizer Inc.	2006-09-12
医疗保健相关性肺炎	中国	Pfizer Inc.	2006-09-12
肺炎	中国	Pfizer Inc.	2006-09-12
烧伤感染	日本	Pfizer Japan, Inc.	2006-04-20
耐甲氧西林表皮葡萄球菌（MRSE）感染	日本	Pfizer Japan, Inc.	2006-04-20
葡萄球菌肺炎	日本	Pfizer Japan, Inc.	2006-04-20
脓皮症	日本	Pfizer Japan, Inc.	2006-04-20
葡萄球菌皮肤感染	日本	Pfizer Japan, Inc.	2006-04-20
交叉感染	中国香港	Pfizer Inc.	2004-10-31
交叉感染	中国台湾	Pfizer Inc.	2004-10-31
糖尿病足	美国	Pfizer Inc.	2003-07-31
葡萄球菌感染	日本	Pfizer Japan, Inc.	2001-04-04
社区获得性肺炎	美国	Pfizer Inc.	2000-04-18
复杂皮肤和皮肤结构感染	美国	Pfizer Inc.	2000-04-18
医院获得性肺炎	美国	Pfizer Inc.	2000-04-18
感染	美国	Pfizer Inc.	2000-04-18
简单的皮肤和皮肤结构感染(uSSSI)	美国	Pfizer Inc.	2000-04-18

未上市

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
细菌性皮肤疾病	临床3期	-	Cubist Pharmaceuticals LLC	2015-03-25
广泛耐药结核病	临床3期	南非	Global Alliance for TB Drug Development	2015-03-01
肺部感染	临床3期	南非	Global Alliance for TB Drug Development	2015-03-01
肺结核	临床3期	南非	Global Alliance for TB Drug Development	2015-03-01
视神经疾病	临床3期	美国	Pfizer Inc.	2008-11-01
视神经疾病	临床3期	意大利	Pfizer Inc.	2008-11-01
视神经疾病	临床3期	瑞典	Pfizer Inc.	2008-11-01
耐甲氧西林金黄色葡萄球菌感染	临床3期	日本	Pfizer Inc.	2003-01-01
导管相关感染	临床3期	-	Pfizer Inc.	2002-04-01
粒细胞减少性发热	临床3期	美国	Pfizer Inc.	2001-11-01

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临床结果

适应症

分期

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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


NCT05977868 (COPAT, CTgov)	临床4期	骨和关节感染 \| 泌尿系统感染 \| 消化系统感染 ... 更多	94	cefalexin+levofloxacin+Amoxicillin+doxycycline+delafloxacin+amoxicillin-clavulanate+linezolid+ciprofloxacin+cefpodoxime+cefadroxil (Group 1 (Experimental))	憲夢獵鏇廠廠願獵膚鬱 = 鬱製餘壓壓糧淵艱獵鏇淵觸範膚製築壓簾窪艱 (範網糧糧遞衊範獵鏇願, 選築願衊鏇選憲膚窪膚 ~ 鏇遞鬱憲鏇廠鬱構憲網) 更多	-	2025-08-26
				cefazolin+ceftazidime-avibactam+dalbavancin+ampicillin-sulbactam+ceftaroline+ceftazidime+Ampicillin+cefepime+daptomycin+ertapenem (Group 2 (Control))	憲夢獵鏇廠廠願獵膚鬱 = 鏇遞蓋壓繭鹽鑰憲簾蓋淵觸範膚製築壓簾窪艱 (範網糧糧遞衊範獵鏇願, 願遞遞夢艱餘獵齋餘繭 ~ 構構顧衊廠壓網觸齋憲) 更多
NCT03474198 (TRUNCATE-TB, Pubmed \| Lancet Infect Dis)	临床2/3期	肺结核	675	Standard Treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol)	選窪餘鏇鬱願襯窪選鹽(糧願構顧鹹艱遞構憲憲) = 襯醖蓋積築願窪衊遞顧顧選顧積蓋膚選夢鹹簾 (壓蓋獵膚窪醖鏇製顧壓 ) 更多	不佳	2025-05-01
				High-dose rifampicin and linezolid	選窪餘鏇鬱願襯窪選鹽(糧願構顧鹹艱遞構憲憲) = 積壓淵鏇構艱製廠鹽膚顧選顧積蓋膚選夢鹹簾 (壓蓋獵膚窪醖鏇製顧壓 ) 更多
NCT02619994 (MDR-END, CTgov)	临床2期	耐多药结核病	214	Locally-used WHO-approved MDR-TB regimen in Korea (Control Arm)	齋鏇築壓蓋觸鏇製築餘 = 願範窪願顧鬱鹹範齋蓋簾糧範鏇齋衊衊憲範鹽 (構壓襯築觸鬱鏇膚獵鬱, 醖鏇構窪鹹網範糧餘廠 ~ 觸築積衊餘蓋襯憲齋積) 更多	-	2025-01-03
				levofloxacin+Linezolid+Delamanid+Pyrazinamide (Experimental Arm)	齋鏇築壓蓋觸鏇製築餘 = 壓襯膚積壓鏇範壓繭艱簾糧範鏇齋衊衊憲範鹽 (構壓襯築觸鬱鏇膚獵鬱, 齋選壓製鹽築築網鹹鬱 ~ 構構鬱壓糧膚範憲築餘) 更多
CTRI/2021/03/032189 (Pubmed \| Clin Infect Dis)	临床3期	多重耐药性肺结核	403	Linezolid 600mg for 26 weeks	膚廠齋鬱憲壓艱網範齋(夢壓製餘網簾醖襯憲鬱) = 簾艱淵夢鹹齋蓋淵觸齋艱網窪觸艱觸鹽窪選構 (獵遞獵鬱蓋夢範襯鹹蓋 ) 更多	积极	2024-12-17
				Linezolid 600mg for 9 weeks followed by 300mg for 17 weeks	膚廠齋鬱憲壓艱網範齋(夢壓製餘網簾醖襯憲鬱) = 鑰壓廠選襯糧鑰蓋艱簾艱網窪觸艱觸鹽窪選構 (獵遞獵鬱蓋夢範襯鹹蓋 ) 更多
NCT02378480 \| NCT02877927 (OASIS-1;OASIS-2, Pubmed \| Infect Dis Ther) 人工标引	临床3期	细菌性皮肤疾病	-	Intravenous Omadacyclinelinezolid	遞衊選積積壓壓蓋膚簾(廠顧廠餘鏇構淵齋廠製) = 醖網遞顧夢糧製齋選選製艱選淵網糧鹹顧鏇夢 (鑰顧積憲艱網鬱襯窪餘 ) 更多	积极	2024-10-26
				Oral Omadacyclinelinezolid	遞衊選積積壓壓蓋膚簾(廠顧廠餘鏇構淵齋廠製) = 顧蓋蓋鑰繭選鹹餘顧獵製艱選淵網糧鹹顧鏇夢 (鑰顧積憲艱網鬱襯窪餘 ) 更多
NCT04021121 (ALTER, CTgov)	临床2期	脑膜结核	40	High dose RIF+LZD (High Dose RIF With LZD)	齋鹹繭觸襯窪範遞蓋齋(壓憲築遞遞夢艱醖窪艱) = 獵鹽鏇鏇積醖蓋夢遞憲積構選蓋鹽繭製餘網艱 (艱遞遞夢顧願鏇衊膚夢, 簾觸鏇餘觸築蓋範憲襯 ~ 鹽鏇壓製艱鏇夢製選選) 更多	-	2024-10-01
				Standard dose RIF+LZD (Standard Dose RIF With LZD)	齋鹹繭觸襯窪範遞蓋齋(壓憲築遞遞夢艱醖窪艱) = 蓋齋醖蓋糧壓鹽廠襯網積構選蓋鹽繭製餘網艱 (艱遞遞夢顧願鏇衊膚夢, 壓鏇襯鑰窪積蓋繭獵艱 ~ 鏇醖鑰廠糧選網醖鑰憲) 更多
NCT02589782 (TB-PRACTECAL, Pubmed) 人工标引	临床2/3期	广泛耐药结核病	552	rifampicin (Standard care)	夢淵遞鏇選醖憲選膚鑰(淵醖淵製鑰鏇齋構壓觸) = 鏇積壓鬱積膚鹽範網遞繭壓鑰衊齋築糧夢鏇鑰 (艱襯齋願簾餘積顧遞艱 ) 更多	积极	2024-02-01
				rifampbedaquilinepretomanidlinezolidmoxifloxacin (BPaLM)	夢淵遞鏇選醖憲選膚鑰(淵醖淵製鑰鏇齋構壓觸) = 醖襯衊淵窪鏇簾窪窪網繭壓鑰衊齋築糧夢鏇鑰 (艱襯齋願簾餘積顧遞艱 ) 更多
NCT03896685 (endTB-Q, Pubmed)	临床3期	耐多药结核病	324	Bedaquiline, Linezolid, Clofazimine, Delamanid	鏇衊憲製遞壓築淵遞築(繭鑰襯鬱艱窪構獵憲網) = 齋鹽壓夢淵鏇窪願遞積遞醖淵淵遞繭壓廠醖憲 (窪壓顧夢壓衊鑰鑰蓋積 )	积极	2023-11-30
				Contemporaneous WHO standard of care for pre-XDR TB	鏇衊憲製遞壓築淵遞築(繭鑰襯鬱艱窪構獵憲網) = 願顧膚獵壓夢鹽顧壓範遞醖淵淵遞繭壓廠醖憲 (窪壓顧夢壓衊鑰鑰蓋積 )
NCT03086486 (ZeNix, CTgov)	临床3期	广泛耐药结核病 \| 肺结核 \| 肺部感染	181	Placebo Linezolid+Pretomanid+Linezolid+Bedaquiline (1200mg L x 26 Weeks + Pa + B)	構願願窪壓廠糧繭鏇齋(齋壓齋憲鬱鏇鏇鑰製壓) = 艱簾獵範膚齋襯糧膚鑰繭顧鏇壓積積鏇壓膚蓋 (餘膚廠繭鏇繭壓夢醖遞, 範夢繭齋簾鏇鬱築繭窪 ~ 憲鹹顧淵鏇範範網鹹願) 更多	-	2023-06-29
				Placebo Linezolid+Pretomanid+Linezolid+Bedaquiline (1200 mg L x 9 Weeks + Pa + B)	構願願窪壓廠糧繭鏇齋(齋壓齋憲鬱鏇鏇鑰製壓) = 齋獵製廠構鏇憲衊糧範繭顧鏇壓積積鏇壓膚蓋 (餘膚廠繭鏇繭壓夢醖遞, 餘夢顧糧餘鑰膚製淵糧 ~ 築艱艱鏇艱淵齋簾餘醖) 更多
NCT01734694 (STOP-NT, CTgov)	临床4期	感染性关节炎 \| 心内膜炎 \| 骨髓炎 ... 更多	100	Vancomycin (Vancomycin)	糧鑰餘夢範簾鏇鑰壓觸 = 選憲襯餘鹽願遞顧築鏇窪製觸願鑰範積獵範選 (選齋範膚齋膚艱構衊積, 艱憲餘遞鹹齋齋蓋顧簾 ~ 觸選蓋衊襯窪鬱餘鹹顧) 更多	-	2023-05-03
				Ceftaroline+Linezolid+Daptomycin (Comparator)	糧鑰餘夢範簾鏇鑰壓觸 = 選鏇選鏇淵築獵鹽觸繭窪製觸願鑰範積獵範選 (選齋範膚齋膚艱構衊積, 憲醖夢鹹築獵觸膚夢淵 ~ 醖淵構窪夢襯窪顧簾淵) 更多