International Journal of Antimicrobial Agents最新文献

英文中文

Antibiotic class comparisons for the treatment of pyelonephritis and complicated urinary tract infections: A systematic review and meta-analysis 治疗肾盂肾炎和并发尿路感染的抗生素类别比较：系统回顾和荟萃分析。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2026-02-01 Epub Date: 2025-12-22 DOI: 10.1016/j.ijantimicag.2025.107696

Digbijay Kunwar , Itay Zahavi , Judit Olchowski , Hagar Dallasheh , Mical Paul

Background

The relative efficacy of antibiotic classes for pyelonephritis and complicated UTI (cUTI) remains unclear, as different antibiotic classes vary in antimicrobial activity, pharmacodynamics and pharmacokinetics.

Methods

Systematic review and meta-analysis. We searched PubMed, Cochrane CENTRAL, clinical-trial registries and conference abstracts through 30 November 2025. Randomised controlled trials comparing antibiotic classes in adults with pyelonephritis/complicated UTI (cUTI) were eligible (PROSPERO CRD42023448020). Five comparisons were analysed: quinolones vs β-lactams, cephalosporins vs penicillins, aminoglycosides vs quinolones or beta-lactams, trimethoprim-sulfamethoxazole vs quinolones or beta-lactams and ESBL-active agents vs non-ESBL-active antibiotics. The primary outcome was clinical cure by day 7. We compiled risk ratios (RRs) with 95% confidence intervals (CI) using fixed-effect meta-analyses. Risk of bias was assessed with ROB 2.0 and evidence certainty using GRADE.

Results

Thirty-seven RCTs were included, comprising 7,904 mainly hospitalized participants (62.7% women). Most had some risk-of-bias concerns. No significant difference in clinical cure was observed with moderate evidence certainty, across all comparisons. Relapse increased significantly with TMP/SMX compared to quinolones or beta-lactams (RR 2.34 [1.29, 4.24]) and microbiological cure improved with ESBL-active antibiotics (RR 1.07 [1.02, 1.13], very low certainty evidence). TMP/SMX increased adverse events and aminoglycosides increased nephrotoxicity and resistance acquisition.

Conclusions

Clinical cure was comparable across all comparisons. This supports basing antibiotic selection on local resistance patterns, patient factors and toxicity profiles rather than presumed class superiority.

背景：不同种类的抗生素治疗肾盂肾炎和合并UTI （cUTI）的相对疗效尚不清楚，因为不同种类的抗生素在抗菌活性、药效学和药代动力学方面存在差异。方法：系统评价和荟萃分析。我们检索了PubMed、Cochrane CENTRAL、临床试验注册库和2025年11月30日的会议摘要。比较成人肾盂肾炎/ cUTI患者抗生素种类的随机对照试验符合条件（PROSPERO CRD42023448020）。分析了五种比较：喹诺酮类与β-内酰胺类、头孢菌素类与青霉素类、氨基糖苷类与喹诺酮类或β-内酰胺类、甲氧苄啶磺胺甲恶唑类与喹诺酮类或β-内酰胺类、esbl活性药物与非esbl活性抗生素。主要终点为第7天临床治愈。我们使用固定效应荟萃分析编制了95%置信区间的风险比（rr）。偏倚风险采用rob2.0评估，证据确定性采用GRADE评估。结果：纳入37项随机对照试验，包括7904名主要住院患者（62.7%为女性）。大多数人都有一些偏见风险的担忧。在所有比较中，没有观察到临床治愈的显著差异，证据确定性中等。与喹诺酮类或β -内酰胺类药物相比，TMP/ SMX组的复发率显著增加（RR为2.34 [1.29,4.24]），eslb活性抗生素组的微生物治愈率提高（RR为1.07[1.02,1.13]，确定性证据非常低）。TMP/ SMX增加了不良事件，氨基糖苷增加了肾毒性和耐药性获得。结论：临床治愈率在所有比较中具有可比性。这支持根据当地的耐药模式、患者因素和毒性特征来选择抗生素，而不是假设的类别优势。

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引用次数: 0

Regorafenib, a multitargeted kinase inhibitor, inhibits enterovirus 71 infection by suppressing the MAPK pathway Regorafenib是一种多靶点激酶抑制剂，通过抑制MAPK途径抑制肠病毒71感染。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2026-02-01 Epub Date: 2026-01-03 DOI: 10.1016/j.ijantimicag.2025.107711

Xinyu Zhang , Yuanyuan Cao , Yu Liu , Shengqun Deng , Shilong Lv , Wangping Peng , Lu Fang , Luyao Zhang , Yaling Wu , Li Yu , Baojing Lu , Shenghai Huang , Qi Tang

Objectives

To investigate the in vitro and in vivo antiviral efficacy and underlying mechanism of regorafenib against Enterovirus 71 (EV71), as no licensed direct-acting antivirals are available for severe cases.

Methods

The inhibitory effect of regorafenib against EV71 was evaluated using qRT‒PCR, Western blot, IF, and CPE assays. The stage of the viral life cycle targeted by regorafenib was determined via time-of-addition, binding and entry assays. In vivo efficacy was assessed in an EV71-infected murine model by monitoring body weight, clinical scores, and viral RNA loads in tissues. The mechanism of action was elucidated by analyzing the effect of regorafenib on the MEK/ERK phosphorylation in the host mitogen-activated protein kinase (MAPK) pathway. A potential interaction with the EV71 capsid protein VP1 was investigated using molecular docking.

Results

Regorafenib demonstrated potent, dose-dependent antiviral activity against EV71 in vitro and exhibited broad-spectrum efficacy against multiple human enteroviruses. In an EV71-infected murine model, oral administration of regorafenib at doses of 1.25 or 2.5 mg/kg/day significantly alleviated infection-associated symptoms and reduced viral loads in key organs. Mechanistic investigations revealed that regorafenib suppressed viral replication by inhibiting the phosphorylation of MEK and ERK in the MAPK pathway. Molecular docking studies further predicted that regorafenib binds to the viral capsid protein VP1, providing a potential structural basis for its antiviral effect.

Conclusions

Our findings establish that regorafenib exhibits inhibitory activity against EV71 in vitro and in vivo, which warrants further preclinical evaluation as a candidate lead compound.

肠病毒71 （EV71）是引起手足口病（手足口病）的主要病原体之一，严重威胁幼儿的健康和安全。目前有EV71 C4疫苗；然而，目前还没有针对严重病例的许可直接抗病毒药物。在这项研究中，我们证明regorafenib是一种临床批准的多靶点激酶抑制剂，具有抗癌应用，对EV71具有有效的抗病毒活性，并且对多种人类肠道病毒具有广谱疗效。在ev71感染的小鼠模型中，口服瑞非尼1.25或2.5 mg/kg/天的剂量可显著缓解感染相关症状，并降低关键器官的病毒载量。机制研究表明，reorafenib通过抑制丝裂原活化蛋白激酶（MAPK）通路中MAPK/ERK激酶（MEK）和细胞外信号调节激酶（ERK）的磷酸化来抑制EV71， MAPK是病毒诱导的信号级联反应，对病毒的发病至关重要。此外，分子对接研究预测reorafenib与EV71衣壳蛋白VP1结合，提示其抗病毒机制的潜在结构基础。总之，我们的研究结果表明瑞非尼对EV71具有抑制活性，值得作为候选先导化合物进行进一步的临床前评估。

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引用次数: 0

Superintegron of Vibrio paracholerae as a reservoir of antibiotic resistance genes 副弧菌作为抗生素抗性基因储存库的超整合子。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2026-02-01 Epub Date: 2025-12-30 DOI: 10.1016/j.ijantimicag.2025.107708

Sergio Mascarenhas Morgado, Erica Lourenço da Fonseca, Ana Carolina Paulo Vicente

引用次数: 0

Development of ceftazidime–avibactam resistance driven by conversion of blaKPC-2 to blaKPC-78 during treatment of ST463 carbapenem-resistant Pseudomonas aeruginosa infection 在ST463耐碳青霉烯假单胞菌感染治疗过程中，由blaKPC-2转化为blaKPC-78驱动头孢他啶-阿维巴坦耐药性的发展

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2026-02-01 Epub Date: 2025-12-26 DOI: 10.1016/j.ijantimicag.2025.107703

Haotian Xu , Tingjuan Zhang , Xueying Cui , Jingyi Guo , Pengpeng Min , Chengjin Wu , Xinyan Tang , Longjie Zhou , Linfang Wang , Xi Li

Objective

The emergence of ceftazidime-avibactam (CZA)-resistant carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a major clinical challenge in contemporary clinical practice. In this study, we report the first identification of bla_KPC-78, which is driven by a mutation from bla_KPC-2 in a clinical CRPA strain.

Methods

Six bla_KPC-78 CRPA isolates, along with two bla_KPC-2 strains from one patient, were subjected to antimicrobial susceptibility testing (AST), whole-genome sequencing (WGS), conjugation, and growth assays. Mechanistic investigations included structural modelling and docking, cloning experiments, efflux inhibition, and reverse transcription quantitative polymerase chain reaction (RT-qPCR).

Results

The emergence of CZA resistance in CRPA isolates was driven by a mutation from bla_KPC-2 to bla_KPC-78 during CZA therapy. The AST results showed that all KPC-78-producing CRPA exhibited a multidrug-resistant phenotype. WGS revealed that these strains belong to ST463, and bla_KPC-78 gene was located in a type I plasmid and carried by the Tn6296 transposon. Additionally, the co-occurrence of efflux pump overexpression and KPC-78 enzyme's stronger binding affinities for both ceftazidime and avibactam contributed to high-level resistance to CZA in CRPA. Moreover, despite the slower logarithmic growth of KPC-78-producing P. aeruginosa in monoculture, in vitro competitive co-culture experiments revealed that it conferred a competitive advantage over the KPC-2-producing strains.

Conclusions

We report the first identification of bla_KPC-78 in CRPA, delineate its evolutionary trajectory, and describe its genetic characteristics. The elevated hydrolytic activity of the KPC-78 producing strain, along with the overexpression of efflux pumps, contributes to its high-level resistance to CZA. Considering the widespread occurrence of ST463 CRPA in China, it is imperative to enhance the surveillance of KPC-producing CRPA.

背景：头孢他啶-阿维巴坦（CZA）耐药碳青霉烯耐药铜绿假单胞菌（CRPA）的出现是当代临床实践中的一个重大挑战。在这项研究中，我们首次在临床CRPA菌株中鉴定出由blaKPC-2突变驱动的blaKPC-78。方法：对6株blaKPC-78 CRPA分离株和1例患者的2株blaKPC-2进行抗菌药敏试验（AST）、全基因组测序（WGS）、偶联和生长试验。机制研究包括结构建模与对接、克隆实验、外排抑制和逆转录定量聚合酶链反应（RT-qPCR）。结果：CRPA分离株CZA耐药性的出现是由CZA治疗期间blaKPC-2突变为blaKPC-78引起的。AST结果显示，所有产生kpc -78的CRPA均表现出多药耐药表型。WGS结果显示，这些菌株属于ST463， blaKPC-78基因位于I型质粒上，由Tn6296转座子携带。此外，外排泵过表达和KPC-78酶对头孢他啶和阿维巴坦的结合亲和力较强，共同导致CRPA对CZA的高水平耐药。此外，尽管单培养中产生kpc -78的铜绿假单胞菌的对数生长速度较慢，但体外竞争共培养实验显示，它比产生kpc -2的菌株具有竞争优势。结论：我们首次在CRPA中发现了blaKPC-78，描绘了其进化轨迹，并描述了其遗传特征。KPC-78产生菌株的水解活性升高，以及外排泵的过度表达，有助于其对CZA的高抗性。考虑到ST463 CRPA在中国的广泛存在，加强对产kpc的CRPA的监测势在必行。

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引用次数: 0

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” 关于“头孢他啶-阿维巴坦与其他适当抗菌药物治疗土耳其产OXA-48或kpc肠杆菌感染的比较：一项多中心回顾性匹配队列研究”的致编辑信的回复。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2026-02-01 Epub Date: 2025-12-11 DOI: 10.1016/j.ijantimicag.2025.107691

Abdullah T. Aslan , Patrick N.A. Harris , David L. Paterson

引用次数: 0

Aztreonam–avibactam pharmacokinetics during extracorporeal membrane oxygenation support: First insights from a case report 阿曲南-阿维巴坦在体外膜氧合支持中的药代动力学：一个病例报告的初步见解。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2026-02-01 Epub Date: 2025-12-10 DOI: 10.1016/j.ijantimicag.2025.107692

Alba Pau-Parra , Sònia Luque , Laura Doménech , María Martínez-Pla , Xavier Nuvials , Manuel Sosa Garay , Ibai Los-Arcos , Aldair Conto , Fernando Lasteros , Elisabet Gallart , Maria Queralt Gorgas Torner , Ricard Ferrer , Jordi Riera

引用次数: 0

Enhanced molecular surveillance for gonococcal resistance during doxycycline post-exposure prophylaxis implementation 在多西环素暴露后预防实施过程中加强淋球菌耐药性的分子监测。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2026-02-01 Epub Date: 2025-12-09 DOI: 10.1016/j.ijantimicag.2025.107689

Ziyuan Zhao , Leshan Xiu , Junping Peng

Objective

The introduction of doxycycline post-exposure prophylaxis (doxy-PEP) as a strategy to reduce the risk of bacterial sexually transmitted infections has raised concerns about the potential for rapid selection of tetracycline resistance and the emergence of ceftriaxone-resistant strains. This study aimed to develop a molecular surveillance method to monitor antimicrobial resistance (AMR) in Neisseria gonorrhoeae (NG) during doxy-PEP implementation.

Methods

We developed a high-resolution melting (HRM) analysis-based molecular assay, termed HRM-doxyPEP, to enhance surveillance of NG AMR. Validation was conducted with strains of known susceptibility profiles, and further evaluation was performed on clinical samples, comparing HRM results with quantitative PCR, whole-genome sequencing, and PCR-sequencing.

Results

The HRM-doxyPEP assay demonstrated high analytical specificity and a detection limit of 20 copies/reaction, enabling the detection of low levels of target DNA in clinical samples. Validation with strains of known susceptibility profiles showed 84% consistency with antimicrobial susceptibility testing results. Clinical sample testing revealed 100% sensitivity and specificity for identifying NG infection, tracking ceftriaxone-resistant FC428-like strains, and detecting tetM associated with tetracycline resistance.

Conclusions

The HRM-doxyPEP assay offers an accurate, affordable, and scalable tool for enhanced molecular surveillance of AMR in NG during doxy-PEP implementation.

多西环素暴露后预防（doxy-PEP）作为一种降低细菌性传播感染风险的策略，已引起人们对四环素耐药性快速选择和头孢曲松耐药菌株出现的可能性的担忧。本研究旨在建立一种监测淋病奈瑟菌（Neisseria gonorrhoeae， NG）在doxy-PEP实施过程中抗菌素耐药性（AMR）的分子监测方法。我们开发了一种基于高分辨率熔融（HRM）分析的分子检测方法，称为HRM- doxypep，以加强对NG AMR的监测。对已知药敏谱的菌株进行验证，并对临床样品进行进一步评价，将HRM结果与qPCR、全基因组测序和pcr测序结果进行比较。HRM-doxyPEP分析具有较高的分析特异性，检测限为20拷贝/反应，能够检测临床样品中低水平的目标DNA。已知菌株的敏感性验证结果与AST结果的一致性为84%。临床样本检测显示，检测NG感染、追踪头孢曲松耐药fc428样菌株以及检测与四环素耐药相关的tetM的敏感性和特异性均为100%。HRM-doxyPEP检测提供了一种准确、经济、可扩展的工具，用于在doxy-PEP实施期间增强NG中AMR的分子监测。

{"title":"Enhanced molecular surveillance for gonococcal resistance during doxycycline post-exposure prophylaxis implementation","authors":"Ziyuan Zhao , Leshan Xiu , Junping Peng","doi":"10.1016/j.ijantimicag.2025.107689","DOIUrl":"10.1016/j.ijantimicag.2025.107689","url":null,"abstract":"<div><h3>Objective</h3><div>The introduction of doxycycline post-exposure prophylaxis (doxy-PEP) as a strategy to reduce the risk of bacterial sexually transmitted infections has raised concerns about the potential for rapid selection of tetracycline resistance and the emergence of ceftriaxone-resistant strains. This study aimed to develop a molecular surveillance method to monitor antimicrobial resistance (AMR) in <em>Neisseria gonorrhoeae</em> (NG) during doxy-PEP implementation.</div></div><div><h3>Methods</h3><div>We developed a high-resolution melting (HRM) analysis-based molecular assay, termed HRM-doxyPEP, to enhance surveillance of NG AMR. Validation was conducted with strains of known susceptibility profiles, and further evaluation was performed on clinical samples, comparing HRM results with quantitative PCR, whole-genome sequencing, and PCR-sequencing.</div></div><div><h3>Results</h3><div>The HRM-doxyPEP assay demonstrated high analytical specificity and a detection limit of 20 copies/reaction, enabling the detection of low levels of target DNA in clinical samples. Validation with strains of known susceptibility profiles showed 84% consistency with antimicrobial susceptibility testing results. Clinical sample testing revealed 100% sensitivity and specificity for identifying NG infection, tracking ceftriaxone-resistant FC428-like strains, and detecting <em>tetM</em> associated with tetracycline resistance.</div></div><div><h3>Conclusions</h3><div>The HRM-doxyPEP assay offers an accurate, affordable, and scalable tool for enhanced molecular surveillance of AMR in NG during doxy-PEP implementation.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107689"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fosfomycin-based combinations against carbapenemase-producing Klebsiella pneumoniae bloodstream infections: Correlating in vitro synergy with clinical outcomes 基于磷霉素的联合治疗产碳青霉烯酶肺炎克雷伯菌血流感染：与临床结果的体外协同作用相关

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI: 10.1016/j.ijantimicag.2025.107687

Melike Törüyenler Coşkunpınar , Güle Çınar , Duygu Öcal , İsmail Balık

Background

Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) poses a significant global health threat due to its limited treatment options and increasing resistance. Fosfomycin (FOF) has regained interest, particularly in combination therapies. This study aimed to evaluate the in vitro synergy of FOF with meropenem (MEM) and polymyxin in CP-Kp bloodstream infections (BSI) and to investigate clinical outcomes.

Methods

Fifty-two patients with CP-Kp BSI who received FOF-based combination therapy (FOF-C) for ≥72 h were evaluated retrospectively for clinical outcomes. Minimum inhibitor concentrations (MICs) were determined on stored isolates: FOF by agar dilution (AD) and broth microdilution, MEM and COL by broth microdilution. In vitro synergy testing of FOF with MEM and COL was performed using the checkerboard method. Data were analysed using logistic regression.

Results

Among 50 isolates, the FOF AD MIC_50/90 were 64/>128 µg/mL. Positive in vitro interactions (synergistic or additive) were observed in 43.5% of isolates for both FOF + MEM and FOF + COL, with no antagonism. The clinical and microbiological response rates were 61.5% and 80.5%, 14- and 30-d mortality rates were 21.2% and 40.4%, respectively. Patients receiving at least one agent with in vitro positive interaction had higher clinical response, but the difference wasn’t significant (73.7% vs. 52.2% P = 0.153). In multivariable analysis, increased FOF AD MIC and Pitt bacteraemia score were associated with clinical nonresponse, while higher COL MIC and Pitt bacteraemia score predicted 30-d mortality.

Conclusions

FOF AD MIC value may have potential as a predictive marker for FOF-C treatment response in CP-Kp BSI and could aid in guiding combination therapy decisions. Larger, prospective studies using standardized synergy testing methods are needed.

背景：产碳青霉烯酶肺炎克雷伯菌（CP-Kp）由于其治疗选择有限和耐药性增加，对全球健康构成重大威胁。磷霉素（FOF）已重新引起人们的兴趣，特别是在联合治疗中。本研究旨在评估FOF与美罗培南（MEM）和多粘菌素在CP-Kp血流感染（BSI）中的体外协同作用，并探讨临床结果。方法：回顾性评价52例接受fof联合治疗(FOF-C)≥72小时的CP-Kp BSI患者的临床结果。对储存的分离株进行mic测定：琼脂稀释法（AD）和肉汤微量稀释法（BMD）测定FOF， BMD测定MEM和COL。采用棋盘法测定FOF与MEM、COL的体外协同作用。数据采用逻辑回归分析。结果：50株分离菌FOF AD MIC50/90为64/ bb0 ~ 128 μg/mL；43.5%的分离株对FOF+MEM和FOF+COL均有正向的体外相互作用（协同或加性），无拮抗作用。临床和微生物应答率分别为61.5%和80.5%，14天和30天死亡率分别为21.2%和40.4%。接受至少一种药物体外正相互作用的患者临床疗效较高，但差异无统计学意义（73.7% vs. 52.2% p=0.153）。在多变量分析中，FOF AD MIC和Pitt菌血症评分（PBS）升高与临床无反应相关，而较高的COL MIC和PBS预测30天死亡率。结论：FOF- AD - MIC值可能作为预测CP-Kp BSI患者FOF- c治疗反应的潜在指标，并有助于指导联合治疗决策。需要使用标准化协同测试方法进行更大规模的前瞻性研究。

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引用次数: 0

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] “抗菌素耐药性措施和COVID-19的出现对整个日本人群抗菌素使用的影响：使用国家索赔数据库的回顾性队列研究”[国际抗微生物药物杂志第67卷（2026）107667]的勘误表。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2026-02-01 Epub Date: 2026-01-03 DOI: 10.1016/j.ijantimicag.2025.107694

Ryuji Koizumi , Shinya Tsuzuki , Yusuke Asai , Kensuke Aoyagi , Norio Ohmagari

引用次数: 0

International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page 国际抗微生物化疗学会（ISAC）新闻和信息页面

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2026-02-01 Epub Date: 2026-01-31 DOI: 10.1016/j.ijantimicag.2026.107719

引用次数: 0

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