International Journal of Antimicrobial Agents最新文献

{"title":"Unravelling AMR dynamics in the rumenofaecobiome: Insights, challenges and implications for One Health","authors":"Ziming Wu ,&nbsp;Mustasim Famous ,&nbsp;Theano Stoikidou ,&nbsp;Freya E.S. Bowden ,&nbsp;Gama Dominic ,&nbsp;Sharon A. Huws ,&nbsp;Fernanda Godoy-Santos ,&nbsp;Linda B. Oyama","doi":"10.1016/j.ijantimicag.2025.107494","DOIUrl":"10.1016/j.ijantimicag.2025.107494","url":null,"abstract":"<div><div>Antimicrobial resistance (AMR) is a critical global threat to human, animal and environmental health, exacerbated by horizontal gene transfer (HGT) via mobile genetic elements. This poses significant challenges that have a negative impact on the sustainability of the One Health approach, hindering its long-term viability and effectiveness in addressing the interconnectedness of global health. Recent studies on livestock animals, specifically ruminants, indicate that culturable ruminal bacteria harbour AMR genes with the potential for HGT. However, these studies have focused predominantly on using the faecobiome as a proxy to the rumen microbiome or using easily isolated and culturable bacteria, overlooking the unculturable population. These unculturable microbial groups could have a profound influence on the rumen resistome and AMR dynamics within livestock ecosystems, potentially holding critical insights for advanced understanding of AMR in One Health. In order to address this gap, this review of current research on the burden of AMR in livestock was undertaken, and it is proposed that combined study of the rumen microbiome and faecobiome, termed the ‘rumenofaecobiome’, should be performed to enhance understanding of the risks of AMR in ruminant livestock. This review discusses the complexities of the rumen microbiome and the risks of AMR transmission in this microbiome in a One Health context. AMR transmission dynamics and methodologies for assessing the risks of AMR in livestock are summarized, and future considerations for researching the impact of AMR in the rumen microbiome and the implications within the One Health framework are discussed.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 1","pages":"Article 107494"},"PeriodicalIF":4.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691995","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":"Host immunity and intracellular bacteria evasion mechanisms: Enhancing host-directed therapies with drug delivery systems","authors":"Jiayang Cai ,&nbsp;Han Zhou ,&nbsp;Mingwei Liu,&nbsp;Dingjian Zhang,&nbsp;Jingxuan Lv,&nbsp;Haokun Xue,&nbsp;Houcheng Zhou,&nbsp;Wenli Zhang","doi":"10.1016/j.ijantimicag.2025.107492","DOIUrl":"10.1016/j.ijantimicag.2025.107492","url":null,"abstract":"<div><div>Host-directed therapies (HDTs) have been investigated as a potential solution to combat intracellular and drug-resistant bacteria. HDTs stem from extensive research on the intricate interactions between the host and intracellular bacteria, leading to a treatment approach that relies on immunoregulation. To improve the bioavailability and safety of HDTs, researchers have utilized diverse drug delivery systems (DDS) to encapsulate and transport therapeutic agents to target cells. In this review, we first introduce the three mechanisms of bactericidal action and intracellular bacterial evasion: autophagy, reactive oxygen species (ROS), and inflammatory cytokines, with a particular focus on autophagy. Special attention is given to the detailed mechanism of xenophagy in clearing intracellular bacteria, a crucial selective autophagy process that specifically targets and degrades intracellular pathogens. Following this, we present the application of DDS to modulate these regulatory methods for intracellular bacteria elimination. By integrating insights from immunology and nanomedicine, this review highlights the emerging role of DDS in advancing HDTs for intracellular bacterial infections and paving the way for innovative therapeutic interventions.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 6","pages":"Article 107492"},"PeriodicalIF":4.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663381","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":"Phylogenetic insights of a human-derived optrA-positive Staphylococcus aureus isolated from a person with chronic diarrhea in China","authors":"Aoxiao Chen ,&nbsp;Hanyu Wang ,&nbsp;Zelin Yan ,&nbsp;Ning Dong ,&nbsp;Rong Zhang ,&nbsp;Yonglu Huang ,&nbsp;Hongwei Zhou","doi":"10.1016/j.ijantimicag.2025.107493","DOIUrl":"10.1016/j.ijantimicag.2025.107493","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 6","pages":"Article 107493"},"PeriodicalIF":4.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648630","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":"Exploring the protective role of recombinant type iii interferons in respiratory infections: Insights from an Mx1-deficient mouse model","authors":"A. Lozhkov ,&nbsp;O. Dobrovolskaya ,&nbsp;E. Romanovskaya-Romanko ,&nbsp;S. Shishlyannikov ,&nbsp;E. Elpaeva ,&nbsp;A. Garshinina ,&nbsp;Y. Zabrodskaya ,&nbsp;A. Shaldzhyan ,&nbsp;V. Egorov ,&nbsp;A. Vasin","doi":"10.1016/j.ijantimicag.2025.107491","DOIUrl":"10.1016/j.ijantimicag.2025.107491","url":null,"abstract":"<div><h3>Background</h3><div>Type III interferons (IFNs) are regarded as safe and effective preventive agents for viral infections of the respiratory tract. The effectiveness of the preventive use of type III IFNs in patients with polymorphisms in critical antiviral ISGs is particularly relevant. We utilized Balb/c mice deficient in the <em>Mx1</em> gene as model organisms.</div></div><div><h3>Methods</h3><div>Recombinant IFNs were administered intranasally one day before infection with the mouse-adapted pandemic strain of influenza A virus (IAV), A/California/07/09 (H1N1pdm09). In the model of mixed infection (sequential infection with IAV at a sublethal dose and <em>Staphylococcus aureus</em>), a bacterial suspension was administered intranasally a day after IAV infection. Influenza nucleoprotein level and bacterial load were assessed in the lungs on the third day post-infection.</div></div><div><h3>Results</h3><div>Type III IFNs demonstrated a protective effect against infection with IAV. A single intranasal administration of IFN-λ protected mice from weight loss, reduced the level of viral nucleoprotein in lung homogenates, and significant differences in survival curves were also observed. In the case of mixed infection, a single intranasal administration of IFN-λ was associated with a decrease in bacterial load in the lungs, and minimal weight loss was observed in the mice.</div></div><div><h3>Conclusion</h3><div>The study demonstrated that IFN-λ can have a protective effect in <em>Mx1</em>-deficient Balb/c mice. These data support the universality of type III IFN use, suggesting that these preventive agents can be effective even in patients with a suboptimal genetic background.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 1","pages":"Article 107491"},"PeriodicalIF":4.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624450","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":"Comparing the Knowledge, Attitudes, and Practices of Antibiotic Use and Antimicrobial Resistance for Cats and/or Dogs amongst Pet Owners in Singapore: A Cross-sectional Study.","authors":"Seema Aithal, Gabriel Toh, Huiling Guo, Zoe Jane-Lara Hildon, Teo Boon Han, Timothy Chua, Angela Chow","doi":"10.1016/j.ijantimicag.2025.107489","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107489","url":null,"abstract":"<p><p>Antibiotic use in pets can contribute to antimicrobial resistance (AMR) in both humans and pets. There is a paucity of data on pet owners' knowledge, attitudes, and practices regarding antibiotic use in pets in Asia, despite increasing pet ownership. Therefore, we conducted a study to compare the knowledge, attitudes and practices of antibiotic use and AMR for pets amongst cat and/or dog owners in Singapore. A cross-sectional survey among 1080 pet owners from 16 veterinary clinics between March 2023 and December 2023 evaluated pet owners' knowledge of antibiotic use, understanding of AMR, and antibiotic practices for their pets. Majority of pet owners were female (63.9%), higher educated (86.9%), owned dogs only (62.2%) and currently working (76.4%). Nearly half (46.3%) of all pet owners had poor knowledge of antibiotic use for pets, with cat owners demonstrating poorer knowledge than dog owners (55.2% vs 43.3%, p<0.001). While only one-third (33.9%) of all pet owners used antibiotics inappropriately, two-thirds (67.1%) demonstrated poor AMR knowledge. Cat owners preferred administering antibiotics in the form of liquids, whilst dog owners in the form of tablets. Pet owners play an important role in antibiotic use in pets. Addressing pet owners' poor knowledge of appropriate antibiotic use and AMR for pets is imperative, to strengthen antimicrobial stewardship efforts via a One Health approach.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107489"},"PeriodicalIF":4.9,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604797","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":"Genetic characterization of extensively drug-resistant blaCTX-M-27 Shigella sonnei clusters among men who have sex with men in a region of northern Spain","authors":"Domingo Fernández Vecilla ,&nbsp;Mikel Joseba Urrutikoetxea Gutiérrez ,&nbsp;María Carmen Nieto Toboso ,&nbsp;Kristina Zugazaga Inchaurza ,&nbsp;Estíbaliz Ugalde Zárraga ,&nbsp;Beatriz Ruiz Estévez ,&nbsp;José Luis Díaz de Tuesta del Arco","doi":"10.1016/j.ijantimicag.2025.107490","DOIUrl":"10.1016/j.ijantimicag.2025.107490","url":null,"abstract":"<div><h3>Objective</h3><div>The convergence of globalization with increased sexual risk behaviours has significantly facilitated the dissemination of multidrug-resistant and extensively drug-resistant clusters of <em>Shigella</em> spp. among men who have sex with men, particularly <em>Shigella sonnei</em> and <em>Shigella flexneri</em>. A cluster of <em>S. sonnei</em> carrying <em>bla</em>_CTX-M-27 caused a European outbreak in 2020–2021, with more than 30 cases in Spain, including two in our institution. In this study, we conducted a retrospective study from October 2022 to December 2023 that included five additional patients with shigellosis caused by a CTX-M-27-producing <em>S. sonnei</em>.</div></div><div><h3>Methods</h3><div>Genetic characterization was assessed by whole-genome sequencing using the MinION Mk1C device (Oxford Nanopore Technologies, Oxford, UK).</div></div><div><h3>Results</h3><div>All the isolates presented IncB/O/K/Z or IncFII plasmids, which carried genes conferring resistance to second- and third-generation cephalosporins, cotrimoxazole, azithromycin and quinolones. SNP analysis revealed that neither the strains within this study nor the UK cluster were related to each other.</div></div><div><h3>Conclusions</h3><div>Different community clusters of extensively drug-resistant <em>S. sonnei</em> strains harbouring <em>bla</em>_CTX-M-27 are spreading in our area, mainly associated with sexual transmission among men who have sex with men.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 6","pages":"Article 107490"},"PeriodicalIF":4.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596788","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":"In reply to the Letter to Editor regarding ‘Renal function and its impact on the concentration of ceftazidime-avibactam: A cross-sectional study’","authors":"Jacopo Angelini ,&nbsp;Simone Giuliano ,&nbsp;Simone Lanini ,&nbsp;Sara Ferin ,&nbsp;Luca Martini ,&nbsp;Stella Cossettini ,&nbsp;Jason Roberts ,&nbsp;Massimo Baraldo ,&nbsp;Carlo Tascini","doi":"10.1016/j.ijantimicag.2025.107480","DOIUrl":"10.1016/j.ijantimicag.2025.107480","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 6","pages":"Article 107480"},"PeriodicalIF":4.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585679","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":"Multiomics informed mathematical model for meropenem and tobramycin against hypermutable Pseudomonas aeruginosa","authors":"J.R. Tait ,&nbsp;A.A. Agyeman ,&nbsp;C. López-Causapé ,&nbsp;D. Deveson-Lucas ,&nbsp;K.E. Rogers ,&nbsp;R. Yadav ,&nbsp;V.E. Rees ,&nbsp;B.S. Shin ,&nbsp;R.L. Nation ,&nbsp;J.D. Boyce ,&nbsp;A. Oliver ,&nbsp;C.B. Landersdorfer","doi":"10.1016/j.ijantimicag.2025.107488","DOIUrl":"10.1016/j.ijantimicag.2025.107488","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Hypermutable &lt;em&gt;P. aeruginosa&lt;/em&gt; isolates frequently display resistance emergence during treatment. Mechanisms of such resistance emergence have not been explored using dynamic hollow-fiber studies and multiomics informed mathematical modeling.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Two hypermutable and heteroresistant &lt;em&gt;P. aeruginosa&lt;/em&gt; isolates, CW8 (MIC&lt;sub&gt;meropenem&lt;/sub&gt;=8 mg/L, MIC&lt;sub&gt;tobramycin&lt;/sub&gt;=8 mg/L) and CW44 (MIC&lt;sub&gt;meropenem&lt;/sub&gt;=4 mg/L, MIC&lt;sub&gt;tobramycin&lt;/sub&gt;=2 mg/L), were studied. Both isolates had genotypes resembling those of carbapenem- and aminoglycoside-resistant strains. Achievable lung fluid concentration-time profiles following meropenem at 1 or 2 g every 8 h (3-h infusion) and tobramycin at 5 or 10 mg/kg body weight every 24 h (0.5-h infusion), in monotherapy and combinations, were simulated over 8 days. Total and resistant bacterial counts were determined. Resistant colonies and whole population samples at 191 h were whole-genome sequenced, and population transcriptomics performed at 1 and 191 h. The multiomics analyses informed mechanism-based modeling of total and resistant populations.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;While both isolates eventually displayed resistance emergence against all regimens, the high-dose combination synergistically suppressed resistant regrowth of only CW8 up to ∼96 h. Mutations that emerged during treatment were in &lt;em&gt;pmrB, ampR&lt;/em&gt;, and multiple efflux pump regulators for CW8, and in &lt;em&gt;pmrB&lt;/em&gt; and PBP2 for CW44. At 1 h, &lt;em&gt;mexB, oprM&lt;/em&gt; and &lt;em&gt;ftsZ&lt;/em&gt; were differentially downregulated in CW8 by the combination. These transcriptomics results informed inclusion of mechanistic synergy in the mechanism-based model for only CW8. At 191 h, norspermidine genes were upregulated (without a &lt;em&gt;pmrB&lt;/em&gt; mutation) in CW8 by the combination, and informed the adaptive loss of synergy in the model.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Multiomics information enabled mechanism-based modeling to describe the bacterial response of both isolates simultaneously.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Importance&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt; causes serious bacterial infections in people with cystic fibrosis (pwCF), and has numerous resistance mechanisms. Current empirical approaches to informing antibiotic regimen selection have important limitations. This study exposed two &lt;em&gt;P. aeruginosa&lt;/em&gt; clinical isolates to concentration-time profiles of meropenem and tobramycin as would be observed in lung fluid of pwCF. The combination elicited different bacterial count profiles between the isolates, despite similar bacterial baseline characteristics. We found differences between the isolates in the expression of a key resistance mechanism against meropenem at 1 h, and expression that implied a loss of cell membrane permeability for tobramycin without the expected DNA mutation. This information enabled mathematical modeling to accurately describe all bacterial p","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 6","pages":"Article 107488"},"PeriodicalIF":4.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Title Page & Editorial Board","authors":"","doi":"10.1016/S0924-8579(25)00042-1","DOIUrl":"10.1016/S0924-8579(25)00042-1","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 4","pages":"Article 107485"},"PeriodicalIF":4.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new perspective on the antimicrobial mechanism of linezolid against Staphylococcus aureus revealed by proteomics and metabolomics analysis","authors":"Dan Luo ,&nbsp;Weile Xie ,&nbsp;Shiwei Ma ,&nbsp;Longlong Wang ,&nbsp;Jianguo Zhu ,&nbsp;Zhe Wang","doi":"10.1016/j.ijantimicag.2025.107470","DOIUrl":"10.1016/j.ijantimicag.2025.107470","url":null,"abstract":"<div><div>Understanding bacterial responses to antimicrobials is crucial for identifying tolerance mechanisms and for developing new therapies. Using mass spectrometry–based metabolomics and proteomics, this study examines the response of <em>Staphylococcus aureus</em> to linezolid (LZD) treatment. Under LZD stress, significant fluctuations were observed in key metabolic pathways such as amino acid biosynthesis and the TCA cycle, alongside a general increase in ribosomal protein complexes. Additionally, LZD disrupted nucleotide metabolism, particularly affecting pyrimidine pathways. Combining LZD with the pyrimidine synthesis inhibitor leflunomide enhanced bactericidal effects both in vitro and in vivo, highlighting the importance of targeting pyrimidine biosynthesis to amplify the antimicrobial efficacy of protein inhibitors. These results underscore downstream metabolic processes as viable targets for synergistic drug combinations, suggesting a strategy to potentially improve the clinical effectiveness of LZD.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 6","pages":"Article 107470"},"PeriodicalIF":4.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572952","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}