International Journal of Antimicrobial Agents最新文献

{"title":"In Vitro Neurotoxicity Comparison: Colistimethate Induces Higher Toxicity Than Colistin via Formaldehyde Accumulation.","authors":"Jing Lu, Yan Zhu, Mengyao Li, Yimin Wu, Jinxin Zhao, Xinpeng Yao, Xiaohan Hu, Lynn Wang, Phillip J Bergen, Nitin Patil","doi":"10.1016/j.ijantimicag.2025.107626","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107626","url":null,"abstract":"<p><p>Colistin as a last-line of defence for treating multidrug-resistant Gram-negative bacterial pathogens, is most commonly administered as its inactive prodrug, colistimethate (CMS), for its reduced nephorotoxity. However, the neurotoxicity of CMS compared to colistin has not been studied. In this study, we conducted cell viability assay and discovered that 0.3 mM CMS demonstrated higher toxicity to human neural SH-SY5Y cells compared to 0.3 mM colistin. The concentration of CMS used in this study was six times the average in vivo concentration. Next, we identified formaldehyde as a significant contributor to the observed toxicity, independent of colistin. We employed LC-MS/MS to measure colistin levels resulting from CMS hydrolysis over time, alongside a kit to quantify formaldehyde production from CMS. RNA-seq analysis of SH-SY5Y cells treated with CMS and colistin revealed that DNA damage and cell cycle pathways were notably affected by CMS-induced neurotoxicity, aligning with previous findings related to formaldehyde treatment. Our results indicate that CMS is more cytotoxic to neural cells than colistin, raising concerns about its potential to impair brain function. Given these findings, careful consideration is warranted before administering high doses of CMS directly to the CNS via intrathecal or intraventricular routes.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107626"},"PeriodicalIF":4.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102770","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":"Adjunctive bacteriophage therapy for refractory / resistant Pseudomonas aeruginosa infections - Bottlenecks and proposed solutions.","authors":"Shimin Jasmine Chung, Shuhua Thong, Dorothy Hui Ling Ng, Lester Jun Long Wong, Tse Hua Nicholas Wong, Tan Thuan Tong, Tan Ban Hock, Andrea Lay-Hoon Kwa","doi":"10.1016/j.ijantimicag.2025.107629","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107629","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107629"},"PeriodicalIF":4.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102767","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":"Resistance of Gram-negative bacteria to aztreonam-avibactam: An evaluation of data from in vitro studies.","authors":"Matthew E Falagas, Laura T Romanos, Dimitrios S Kontogiannis, Charalampos Filippou","doi":"10.1016/j.ijantimicag.2025.107624","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107624","url":null,"abstract":"<p><strong>Introduction: </strong>Aztreonam-avibactam is a new combination antibiotic with a broad spectrum of activity against Enterobacterales and lactose non-fermenting Gram-negative bacteria. We evaluated the available data on resistance to aztreonam-avibactam.</p><p><strong>Methods: </strong>We performed a thorough search of four databases for studies that included data on the antimicrobial susceptibility of Enterobacterales and lactose non-fermenting Gram-negative bacterial clinical isolates to aztreonam-avibactam. Data were grouped based on bacterial species (Enterobacterales and lactose non-fermenting Gram-negative bacteria) and whether the studied isolates were consecutive (non-selected) or selected. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint of resistance to aztreonam-avibactam for Enterobacterales (MIC > 4 mg/L) or the specific breakpoints reported by the authors for lactose non-fermenting Gram-negative bacteria were used.</p><p><strong>Results: </strong>Seventy studies reported on in vitro susceptibility testing and mechanisms of antimicrobial resistance of a total of 520,606 clinical isolates (490,231 Enterobacterales and 30,375 lactose non-fermenting Gram-negative isolates). The proportion of Enterobacterales resistant to aztreonam-avibactam was very small in collections of consecutive (non-selected) isolates, specifically 0-1.8% across 7 studies, when a resistance breakpoint of MIC > 4 mg/L was used. Higher proportions of resistance were found in selected Enterobacterales isolates (34 studies), as well as in consecutive (2 studies) and selected (3 studies) lactose non-fermenting Gram-negative isolates, especially Acinetobacter baumannii.</p><p><strong>Conclusion: </strong>The resistance of Enterobacterales clinical isolates to aztreonam-avibactam is rare. However, the noted resistance of selected Enterobacterales as well as consecutive and selected lactose non-fermenting Gram-negative isolates to aztreonam-avibactam suggests that its use should be based on in vitro antimicrobial susceptibility testing.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107624"},"PeriodicalIF":4.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102828","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":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2025.107606","DOIUrl":"10.1016/j.ijantimicag.2025.107606","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 5","pages":"Article 107606"},"PeriodicalIF":4.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057412","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":"Therapeutic Drug Monitoring of Isavuconazole: Trends and Update.","authors":"Zhaoyi Tan, Na Zhang, Beibei Liang, Nan Bai, Yun Cai","doi":"10.1016/j.ijantimicag.2025.107619","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107619","url":null,"abstract":"<p><p>Isavuconazole (ISA) is a triazole antifungal agent that has been approved for the treatment of invasive aspergillosis or mucormycosis in both children and adults. While the pharmacokinetic features of ISA identified during clinical development have not provided a clear need for therapeutic drug monitoring (TDM), emerging evidence suggests that TDM may be warranted in specific clinical scenarios where confirming drug exposure is critical. This article summarizes the populations requiring exposure verification and found subgroups such as pediatric patients, critically ill patients, those on extracorporeal membrane oxygenation (ECMO), renal replacement therapy (RRT), females and patients with high body mass index (BMI) or Sequential Organ Failure Assessment (SOFA) scores appear associated with reduced ISA exposure. Conversely, low BMI, prolonged use, larger dose, liver dysfunction, older age, Asian race, and cotreatment with CYP3A4/5 inhibitors correlate with increased ISA exposure. While the optimal therapeutic range continues to be refined, maintaining trough concentrations between 2.0 mg/L and approximately 5.0 mg/L in these populations is generally supported for these populations to optimize efficacy while minimizing the risk of toxicity.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107619"},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064570","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":"Evaluation of the effect of two adjuvants coadministered with nasal recombinant hemagglutinin influenza vaccine on immune cells in mice.","authors":"Hideaki Mabuchi, Toshiaki Kawano, Ryosuke Gobaru, Kazuhiro Yoshinaga, Ayako Ueo, Kaoru Hashimoto, Misaki Iwata, Takashi Hirano","doi":"10.1016/j.ijantimicag.2025.107617","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107617","url":null,"abstract":"<p><p>Vaccination is the most potent and cost-effective way to combat the threat of influenza outbreaks. Strategies to enhance influenza vaccine immunogenicity include the use of high antigen dose vaccines and the inclusion of an appropriate adjuvant. The benefits of adjuvants include enhanced immunogenicity, antigen-sparing, and greater duration of protection. However, adjuvants can increase vaccine reactogenicity and may adversely impact vaccine safety; hence, both risks and benefits need to be carefully considered when adding adjuvants to a vaccine. In this study, we examined the efficacy of aluminum hydroxide (alum), a representative Th2-type adjuvant, and CpG oligodeoxynucleotide (CpG ODN), a Toll-like receptor 9 agonist, as adjuvants for the influenza vaccine in mice. BALB/c mice were intranasally administered recombinant hemagglutinin (HA) H1N1 vaccine formulated with or without alum and/or CpG ODN. The double adjuvanted vaccine was effective for inducing B cells and NK cells in the lymph node, and B cells in the lung after infection. Additionally, double adjuvants were observed to be effective for antibody production and immune cell activation in various organs, in addition to suppressing side effects. Intranasally-administered double adjuvanted vaccines may serve as an effective means to prevent infection and to reduce side effects of the influenza vaccine.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107617"},"PeriodicalIF":4.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052943","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":"Emergence of IncHI2-ST3 plasmid co-harboring bla_NDM-5, mcr-1.1, and fosA3 in Escherichia coli from a healthy individual in China.","authors":"Xiao-Juan Gao, Chao Yue, Lu- Dan Xiao, Yi-Hua Cai, Lu-Chao Lv, Jian-Hua Liu, Hong-Mei Mo","doi":"10.1016/j.ijantimicag.2025.107615","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107615","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107615"},"PeriodicalIF":4.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052951","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":"Added-value of high-throughput sequencing for early detection of HSV-2 resistant subpopulations in the helicase-primase inhibitors era: A case report.","authors":"A Renzoni, D Neofytos, L Royston, C Espinasse, F Laubscher, E Calfapietra, F Morfin, M Schibler, E Frobert","doi":"10.1016/j.ijantimicag.2025.107616","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107616","url":null,"abstract":"<p><p>Immunocompromised patients are at high risk of developing acyclovir-resistant (ACV) herpes simplex virus (HSV) infections. Helicase-primase inhibitors, including pritelivir (PTV), represent an antiviral option to nephrotoxic alternatives. This report describes the course of an immunocompromised patient infected with HSV-2 treated with PTV and highlights the importance of high throughput sequencing (HTS) for resistance emergence monitoring. After 7 months of ACV treatment, resistance was detected and associated with the emergence of minority subpopulations. Several PTV courses were then administered, which were associated with clinical improvement. HTS technologies enhance sensitivity over conventional methods and provide valuable insights for managing antiviral resistance. Continuous monitoring and research to elucidate the functional impact of specific mutations of unknown significance on drug resistance are essential for building robust HSV resistance databases.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107616"},"PeriodicalIF":4.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052922","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":"Interferon-based optimal antiviral strategies in underage patients with chronic hepatitis B: A propensity score-weighted cohort study","authors":"Limin Wang ,&nbsp;Meina Li ,&nbsp;Yi Dong ,&nbsp;Xiaofang Yu ,&nbsp;Jing Chen ,&nbsp;Yaojie Kang ,&nbsp;Weiwei Liu ,&nbsp;Pan Zhao","doi":"10.1016/j.ijantimicag.2025.107618","DOIUrl":"10.1016/j.ijantimicag.2025.107618","url":null,"abstract":"<div><h3>Objectives</h3><div>Effective treatment of chronic hepatitis B (CHB) in childhood is critical to achieve the goal of eliminating hepatitis B. This study aims to assess the real-world efficacy and safety of different interferon(IFN)-based antiviral strategies in CHB children.</div></div><div><h3>Methods</h3><div>CHB children with elevated ALT or aspartate aminotransferase (AST) and measurable HBV DNA were included. A propensity score weighted analysis was performed and rate of serum hepatitis B surface antigen (HBsAg) loss was the main outcome measure.</div></div><div><h3>Results</h3><div>Totally, 809 patients were enrolled and divided according to different antiviral regimens, including 163 with IFN monotherapy, 325 with IFN-nucleos(t)ide analogues(NA) sequential therapy and 321 with de novo IFN and NA combination therapy. Mean age were 5.9 ± 4.0 years. Median follow-up time was 78.4 months. Generalized overlap weighting analysis showed that de novo IFN and NA combination therapy and IFN monotherapy were better than IFN<img>NA sequential therapy but that no significant difference (<em>P</em> = 0.5999) existed between IFN monotherapy and de novo IFN and NA combination therapy. In the sensitivity analysis, the outcomes from inverse probability of treatment weighting were consistent with those from generalized overlap weighting, but no significant difference (<em>P</em> = 0.0605) was revealed between IFN monotherapy and IFN<img>NA sequential therapy in the multivariable analysis using crude data. Serious adverse events were not observed among the patients.</div></div><div><h3>Conclusions</h3><div>In this cohort study involving the hitherto largest sample of underage CHB patients, IFN<img>NA sequential treatment, though it is commonly used, seems suboptimal in HBsAg clearance. Our results favour the combination of IFN and NA at inception.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107618"},"PeriodicalIF":4.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145053031","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":"Esculetin mitigates MRSA pathogenicity via innovative multitarget inhibition of staphylococcus aureus sortase a, coagulase, and von Willebrand factor-binding protein","authors":"Chi Zhang ,&nbsp;Deli Li ,&nbsp;Min Cheng ,&nbsp;Li Wang ,&nbsp;Bingmei Wang ,&nbsp;Lina Wang","doi":"10.1016/j.ijantimicag.2025.107609","DOIUrl":"10.1016/j.ijantimicag.2025.107609","url":null,"abstract":"<div><div>The global proliferation of antibiotic-resistant <em>Staphylococcus aureus</em>, particularly methicillin-resistant <em>Staphylococcus aureus</em> (MRSA), highlights the urgent need for innovative antivirulence strategies. The redundancy and multiplicity of virulence factors produced by <em>S. aureus</em> necessitate interventions capable of concurrently targeting multiple virulence mechanisms. In this study, we identified esculetin, a natural compound, through comprehensive screening of a compound library. Esculetin uniquely targets sortase A (SrtA), coagulase (Coa), and von Willebrand factor-binding protein (vWbp) without inhibiting bacterial growth <em>in vitro</em>. Esculetin significantly attenuated SrtA-mediated MRSA USA300 strain invasion and biofilm formation while also inhibiting the coagulase activities of both vWbp and Coa. Using fluorescence resonance energy transfer (FRET), fluorescence quenching, and thermal shift assays, we confirmed direct binding interactions between esculetin and SrtA, Coa, and vWbp. In vivo studies demonstrated that esculetin significantly reduced MRSA virulence in <em>Galleria mellonella</em> larvae. Notably, the combination of esculetin and vancomycin markedly enhanced the therapeutic efficacy against MRSA USA300-induced pneumonia and skin infections in murine models, providing superior protection compared with vancomycin monotherapy. This study presents the first comprehensive demonstration of a natural compound capable of simultaneously inhibiting multiple virulence factors of <em>S. aureus</em>. The multitarget inhibition strategy of esculetin represents a promising advancement in combating antibiotic-resistant <em>S. aureus</em> infections by enhancing the therapeutic potential of existing antibiotics and reducing the likelihood of resistance development.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107609"},"PeriodicalIF":4.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033325","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}