International Journal of Antimicrobial Agents最新文献

{"title":"Risk of infective endocarditis in oncohaematological patients undergoing active treatment with Enterococcus faecalis bloodstream infection: A retrospective multicentre study","authors":"Miguel Ángel Consuegra Pérez ,&nbsp;Sara Grillo ,&nbsp;Alexander Rombauts ,&nbsp;María Alba Rivera Martínez ,&nbsp;Anna Falcó-Roget ,&nbsp;Adaia Albasanz-Puig ,&nbsp;Belén Viñado-Pérez ,&nbsp;Nuria Fernández-Hidalgo ,&nbsp;Laura Camps-Relats ,&nbsp;Alba Bergas ,&nbsp;Julia Laporte-Amargos ,&nbsp;Joaquín López-Contreras ,&nbsp;Laura Escolà-Vergé","doi":"10.1016/j.ijantimicag.2025.107706","DOIUrl":"10.1016/j.ijantimicag.2025.107706","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Enterococcus faecalis</em> bloodstream infections (EF-BSIs) are a common cause of infective endocarditis (IE). Recent guidelines consider <em>E. faecalis</em> bacteraemia a major criterion for IE and recommend systematic echocardiographic screening. The objective of this study was to describe the risk of IE in patients with an EF-BSI and an active oncohaematological malignancy.</div></div><div><h3>Methods</h3><div>We conducted a retrospective multicentre cohort study across three cancer centres in Barcelona, Spain, including all consecutive adults with EF-BSI and active oncohaematological malignancy who had received oncologic treatment within the previous 3 months from January 2014 to December 2023. Patients were identified via microbiology databases. The primary outcome was a diagnosis of definite IE based on European Society of Cardiology criteria. Secondary outcomes included 30-d mortality, 6-month relapse, and cumulative mortality.</div></div><div><h3>Results</h3><div>A total of 148 patients were included (median age 64.5 y [IQR 57–72]; 53% male). Eighty (54%) patients had a haematological malignancy, and 68 (46%) a solid tumour. Prosthetic heart valves were present in 4 (3%) patients. Most common BSI sources were primary (39, 26%), urinary tract (36, 24%), abdominal or biliary tract (36, 24%), and central venous catheter-related infections (33, 22%). Echocardiography was performed in 22 patients (15%), with only 2 (1%) diagnosed with definite IE: one had a prosthetic valve, and both had persistent bacteraemia. The 30-d mortality rate was 29% and the 6-month cumulative mortality was 55%. Six patients (7%) experienced relapse, with no new IE diagnoses.</div></div><div><h3>Conclusions</h3><div>Systematic IE screening may not be warranted in this population and should instead be individualised on the basis of clinical risk factors.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107706"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850087","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}

{"title":"Ceftazidime/avibactam and ceftolozane/tazobactam for severe paediatric infections: A systematic review, meta-analysis, and evidence map","authors":"Paula Pimenta-de-Souza ,&nbsp;Alice Ramos-Silva ,&nbsp;Valcieny Sandes ,&nbsp;Patrícia Portella ,&nbsp;Thaís Gouvêa ,&nbsp;Fernando Fernandez-Llimos ,&nbsp;Elisangela Costa Lima","doi":"10.1016/j.ijantimicag.2025.107710","DOIUrl":"10.1016/j.ijantimicag.2025.107710","url":null,"abstract":"<div><h3>Background</h3><div>The growing prevalence of multidrug-resistant Gram-negative bacilli poses major challenges to the management of severe paediatric infections. Ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) are newer β-lactam/β-lactamase inhibitor combinations with established efficacy in adults.</div></div><div><h3>Objective</h3><div>To synthesize current evidence on the efficacy, effectiveness, and safety of CZA and C/T in hospitalized children with severe infections.</div></div><div><h3>Methods</h3><div>We conducted a systematic review, meta-analysis, and evidence map (PROSPERO CRD420251025715). Searches were performed in PubMed, Scopus, CENTRAL, Epistemonikos, LILACS, SciELO, and Web of Science. Eligible designs included randomized controlled trials (RCTs), cohort studies, case series, and case reports evaluating CZA or C/T for complicated intra-abdominal infections, complicated urinary tract infections (cUTI), pneumonia, or bacteraemia in patients aged 0–18 y. The primary outcome was 30-d mortality; secondary outcomes were clinical and microbiological cure and adverse events.</div></div><div><h3>Results</h3><div>Nineteen studies (4 RCTs, 9 case series, 6 case reports) involving 472 patients were included. Sixteen studies evaluated CZA and three evaluated C/T. All RCTs were phase II, industry-sponsored, and excluded critically ill children and carbapenem-resistant infections. According to the updated RoB 2 assessment, two trials had overall low risk of bias, and two presented some concerns, mainly related to missing outcome data. No deaths occurred in RCTs, whereas observational studies reported 8% mortality. Clinical and microbiological cure exceeded 80% across study designs. Adverse events were generally infrequent; neonatal events clustered in case series, but evidence was insufficient for statistical comparison across age groups. Certainty of evidence ranged from moderate (cUTI with susceptible pathogens) to very low (pneumonia and resistant infections).</div></div><div><h3>Conclusions</h3><div>CZA and C/T appear promising for paediatric cUTI and complicated intra-abdominal infections, but the evidence base remains narrow and largely dependent on small, industry-funded trials. Independent RCTs including critically ill children and resistant infections are urgently needed.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107710"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905589","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}

{"title":"Title Page & Editorial Board","authors":"","doi":"10.1016/S0924-8579(26)00016-6","DOIUrl":"10.1016/S0924-8579(26)00016-6","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107727"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189071","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}

{"title":"Vancomycin clearance compared to creatinine clearance by timed urine collection in the intensive care unit","authors":"Andrew Chantha Hean ,&nbsp;Rinoj Mathew ,&nbsp;Frank Chu ,&nbsp;Linda Awdishu","doi":"10.1016/j.ijantimicag.2025.107704","DOIUrl":"10.1016/j.ijantimicag.2025.107704","url":null,"abstract":"<div><h3>Objective</h3><div>Prior literature elucidating the ratio of vancomycin clearance by the kidneys to creatinine clearance is conflicting. Further studies are warranted evaluating vancomycin clearance, especially in the critically ill population.</div></div><div><h3>Methods</h3><div>This retrospective exploratory analysis includes data from a decade of pulmonary/medical or cardiac ICU admissions where a serum creatinine, vancomycin concentration, and 24-hour timed urine collection were obtained within a 72-hour period. Patients with dialysis prior to, or 48 hours after, urine collection were excluded. The primary outcome was the ratio of vancomycin clearance (CLv) to creatinine clearance measured by timed urine collection (mCLcr). Exploratory outcomes also included (1) P30 accuracy and bias of CLv, BSA adjusted 2021 CKD-Epidemiology Collaboration (EPI) creatinine eGFR, Jelliffe creatinine clearance, and Cockcroft-Gault creatinine clearance equations when compared to mCLcr; (2) the correlations of clearances to mCLcr; and (3) the number of patients with augmented renal clearance for each kidney function estimating equation.</div></div><div><h3>Results</h3><div>A total of 56 eligible subjects were analysed. The ratio of CLv to mCLcr was 0.64. Although CLv showed the lowest P30 accuracy, it was the most correlated with mCLcr along with the 2021 CKD-EPI creatinine eGFR to mCLcr.</div></div><div><h3>Conclusions</h3><div>In critically ill patients who warrant medical, pulmonary, or cardiac ICU admission, the ratio of total vancomycin clearance to mCLcr measured by timed urine collection may differ from other populations. CLv and the 2021 CKD-EPI creatinine equation may be more correlated to mCLcr by timed urine collection. Larger studies are needed to confirm these results.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107704"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850061","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}

{"title":"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","authors":"Danni Pu ,&nbsp;Xianxia Zhuo ,&nbsp;Rongrong Song ,&nbsp;Chunhui Wang ,&nbsp;Jiankang Zhao ,&nbsp;Bin Cao","doi":"10.1016/j.ijantimicag.2025.107693","DOIUrl":"10.1016/j.ijantimicag.2025.107693","url":null,"abstract":"<div><h3>Objectives</h3><div>Cefiderocol is an ultimate antibiotic option for Carbapenem-resistant hypervirulent <em>Klebsiella pneumoniae</em> (CR-hvKP). While resistance often involves metallo-β-lactamases, mechanisms in KPC-producing strains are unclear. This study aimed to elucidate novel cefiderocol resistance mechanisms in a clinical KPC-producing ST11-KL64 CR-hvKP isolate.</div></div><div><h3>Methods</h3><div>Cefiderocol-resistant mutants were generated through <em>in vitro</em> experimental evolution. Resistance-associated mutations were identified by whole-genome sequencing. Transcriptomic and proteomic analyses were performed to characterize global regulatory changes and were validated by qRT-PCR and targeted genetic manipulation. Additional tests examined siderophore production, intracellular iron levels, bacterial fitness, oxidative stress tolerance, and macrophage survival.</div></div><div><h3>Results</h3><div>All high-level cefiderocol-resistant mutants acquired a gain-of-function mutation in the sensor kinase EnvZ (V145G). Integrated transcriptomic and proteomic analyses showed that the <em>envZ</em> mutation drove marked downregulation of catecholate siderophore receptors (<em>cirA</em> and <em>fepA</em>), impairing cefiderocol uptake. In parallel, the TonB–ExbB–ExbD energy transduction complex was independently and stably downregulated, synergistically contributing to resistance. Notably, <em>envZ</em> mutation–associated repression of the enterobactin biosynthesis gene <em>entB</em> paradoxically increased cefiderocol susceptibility, indicating a regulatory trade-off. Resistant mutants exhibited reduced siderophore production, impaired intracellular iron accumulation, and significant fitness costs, including attenuated growth, reduced oxidative stress tolerance, and decreased survival within macrophages.</div></div><div><h3>Conclusions</h3><div>In conclusion, this work uncovers a novel cefiderocol resistance mechanism in KPC-producing ST11-KL64 CR-hvKp, initiated by the <em>envZ</em> mutation, which causes the downregulation of catecholate siderophore receptors. This receptor repression, combined with the stable downregulation of the TonB-ExbB-ExbD energy complex, severely impairs cefiderocol's “Trojan horse” active uptake. This resistance mechanism is accompanied by a fitness trade-off, providing critical insights into the evolution of these superbugs.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107693"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800434","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}

{"title":"Formation of a novel multiresistance plasmid co-carrying tigecycline, carbapenem, and other resistance genes by recombination during conjugative transfer in Klebsiella pneumoniae","authors":"Runhao Yu ,&nbsp;Zhong Chen ,&nbsp;Stefan Schwarz ,&nbsp;Hong Yao ,&nbsp;Chenglong Li ,&nbsp;Xiang-Dang Du","doi":"10.1016/j.ijantimicag.2025.107683","DOIUrl":"10.1016/j.ijantimicag.2025.107683","url":null,"abstract":"<div><h3>Objective</h3><div><em>Klebsiella pneumoniae</em> is a major global nosocomial pathogen, and strains acquiring extended-spectrum β-lactamase (ESBL) or carbapenemase resistance genes exhibit extensive clinical drug resistance, posing a serious public health threat. This study aimed to characterize the genetic features and transferability of resistance determinants in a clinically isolated multidrug-resistant <em>K. pneumoniae</em> strain.</div></div><div><h3>Methods</h3><div>A multidrug-resistant <em>K. pneumoniae</em> strain was isolated from clinical samples. Whole-genome sequencing was performed to identify the resistance genes carried by the strain and the transposase sequences within the genetic environment of the target resistance genes. Conjugative transfer experiments were conducted to verify the transferability of the identified resistance genes and their genetic recombination characteristics.</div></div><div><h3>Results</h3><div>The clinical isolate was confirmed to co-carry a <em>tet</em>(A) variant, <em>tmexCD2-toprJ2</em>, and <em>bla</em>_NDM-1 resistance genes. Whole-genome sequencing revealed the presence of IS<em>26</em>, IS<em>3000</em>, and ∆<em>tnpA</em> transposase sequences in the genetic environment of <em>tet</em>(A)v and <em>bla</em>_NDM-1 genes. Conjugative transfer experiments verified the transferability of the different resistance genes, and notably, recombination and co-transfer events of <em>tet</em>(A)v and <em>bla</em>_NDM-1 genes were detected within the conjugative plasmid of the strain.</div></div><div><h3>Conclusions</h3><div>Transposases play a crucial role in the formation of complex multidrug-resistant <em>K. pneumoniae</em> strains. The findings of this study provide a novel perspective and critical evidence for elucidating the antimicrobial resistance mechanisms and dissemination pathways of multidrug-resistant <em>K. pneumoniae</em>.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107683"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654199","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}

{"title":"ATP-binding cassette transporters mediate and regulate metronidazole resistance in Clostridioides difficile","authors":"Teng Xu ,&nbsp;Ying Zhou ,&nbsp;Qingqing Xu ,&nbsp;Li Wang ,&nbsp;Yu Zhou ,&nbsp;Shi Wu ,&nbsp;Haihui Huang","doi":"10.1016/j.ijantimicag.2025.107709","DOIUrl":"10.1016/j.ijantimicag.2025.107709","url":null,"abstract":"<div><h3>Objective</h3><div>Metronidazole (MTZ) resistance in <em>Clostridioides difficile</em> is associated with decreased efficacy of MTZ. We studied the MTZ-resistant <em>C. difficile</em> strain sh182IR (minimum inhibitory concentration [MIC] = 32 mg/L) to characterize the role of ATP-binding cassette (ABC) family transporters in MTZ resistance in <em>C. difficile</em>. The strain overexpresses ABC multidrug efflux pump components.</div></div><div><h3>Methods</h3><div>In strain sh182IR, ClosTron mutagenesis was applied to disrupt <em>cd17530</em>, a gene encoding the ABC transporter ATP-binding protein, and the effects on efflux capacity and MIC of MTZ were evaluated. The upstream regulatory gene <em>cd17520</em> was also sequenced.</div></div><div><h3>Results</h3><div>Disruption of <em>cd17530</em> reduced the efflux capacity of fluorescent substrates and MIC of MTZ in <em>C. difficile</em> sh182IR. Repair of <em>cd17530</em> successfully restored the MTZ MIC and efflux capacity of the strain. We also confirmed that the upstream TetR/AcrR family transcription factor gene <em>cd17520</em> in sh182IR harbours a frameshift mutation. This mutation resulted in the loss of function of the peptide chain encoded by the gene and upregulation of cd17530-17540-17550.</div></div><div><h3>Conclusions</h3><div>The frameshift mutation in the transcriptional repressor <em>cd17520</em>, which results in the derepression of the cd17530-17540-17550 operon, contributes to ABC transporter-mediated MTZ resistance in <em>C. difficile</em>.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107709"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905677","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}

{"title":"Antibiotic class comparisons for the treatment of pyelonephritis and complicated urinary tract infections: A systematic review and meta-analysis","authors":"Digbijay Kunwar ,&nbsp;Itay Zahavi ,&nbsp;Judit Olchowski ,&nbsp;Hagar Dallasheh ,&nbsp;Mical Paul","doi":"10.1016/j.ijantimicag.2025.107696","DOIUrl":"10.1016/j.ijantimicag.2025.107696","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107696"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827746","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}

{"title":"Regorafenib, a multitargeted kinase inhibitor, inhibits enterovirus 71 infection by suppressing the MAPK pathway","authors":"Xinyu Zhang ,&nbsp;Yuanyuan Cao ,&nbsp;Yu Liu ,&nbsp;Shengqun Deng ,&nbsp;Shilong Lv ,&nbsp;Wangping Peng ,&nbsp;Lu Fang ,&nbsp;Luyao Zhang ,&nbsp;Yaling Wu ,&nbsp;Li Yu ,&nbsp;Baojing Lu ,&nbsp;Shenghai Huang ,&nbsp;Qi Tang","doi":"10.1016/j.ijantimicag.2025.107711","DOIUrl":"10.1016/j.ijantimicag.2025.107711","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the <em>in vitro</em> and <em>in vivo</em> antiviral efficacy and underlying mechanism of regorafenib against Enterovirus 71 (EV71), as no licensed direct-acting antivirals are available for severe cases.</div></div><div><h3>Methods</h3><div>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. <em>In vivo</em> 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.</div></div><div><h3>Results</h3><div>Regorafenib demonstrated potent, dose-dependent antiviral activity against EV71 <em>in vitro</em> 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.</div></div><div><h3>Conclusions</h3><div>Our findings establish that regorafenib exhibits inhibitory activity against EV71 <em>in vitro</em> and <em>in vivo</em>, which warrants further preclinical evaluation as a candidate lead compound.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107711"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905623","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}

{"title":"Superintegron of Vibrio paracholerae as a reservoir of antibiotic resistance genes","authors":"Sergio Mascarenhas Morgado,&nbsp;Erica Lourenço da Fonseca,&nbsp;Ana Carolina Paulo Vicente","doi":"10.1016/j.ijantimicag.2025.107708","DOIUrl":"10.1016/j.ijantimicag.2025.107708","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107708"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889237","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}