International Journal of Antimicrobial Agents最新文献

{"title":"Fosfomycin-based combinations against carbapenemase-producing Klebsiella pneumoniae bloodstream infections: Correlating in vitro synergy with clinical outcomes","authors":"Melike Törüyenler Coşkunpınar ,&nbsp;Güle Çınar ,&nbsp;Duygu Öcal ,&nbsp;İsmail Balık","doi":"10.1016/j.ijantimicag.2025.107687","DOIUrl":"10.1016/j.ijantimicag.2025.107687","url":null,"abstract":"<div><h3>Background</h3><div>Carbapenemase-producing <em>Klebsiella pneumoniae</em> (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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>Among 50 isolates, the FOF AD MIC_50/90 were 64/&gt;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% <em>P</em> = 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107687"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696113","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":"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]","authors":"Ryuji Koizumi ,&nbsp;Shinya Tsuzuki ,&nbsp;Yusuke Asai ,&nbsp;Kensuke Aoyagi ,&nbsp;Norio Ohmagari","doi":"10.1016/j.ijantimicag.2025.107694","DOIUrl":"10.1016/j.ijantimicag.2025.107694","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107694"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900364","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.2026.107719","DOIUrl":"10.1016/j.ijantimicag.2026.107719","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107719"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073945","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":"Downregulation of an NfsA-like nitroreductase causes metronidazole resistance in Gardnerella vaginalis","authors":"Ana Paunkov ,&nbsp;Anna-Lena Mayr ,&nbsp;Vera Oberbauer ,&nbsp;Timo Schwebs ,&nbsp;Lorenzo Corsini ,&nbsp;David Leitsch","doi":"10.1016/j.ijantimicag.2025.107681","DOIUrl":"10.1016/j.ijantimicag.2025.107681","url":null,"abstract":"<div><h3>Objectives</h3><div>The facultatively anaerobic or microaerophilic bacteria of the genus <em>Gardnerella</em> are the most common species associated with bacterial vaginosis (BV). The treatment of BV is greatly complicated by the high rates of resistance to metronidazole and clindamycin among <em>Gardnerella</em> strains. We wanted to identify factors contributing to metronidazole resistance in <em>G. vaginalis</em> and performed high-throughput mass spectrometry on a selection of susceptible and resistant strains.</div></div><div><h3>Methods</h3><div>We wanted to identify factors contributing to metronidazole resistance in <em>G. vaginalis</em> and performed high-throughput mass spectrometry on a selection of susceptible and resistant strains.</div></div><div><h3>Results</h3><div>We identified the downregulation of a novel nitroreductase, GvNR1, as the only relevant change in protein expression in a metronidazole-resistant derivative of the susceptible type of strain ATCC 14018 (emended <em>Gardnerella</em> genospecies 1; i.e. <em>G. vaginalis</em> sensu stricto). When tested in in vitro enzyme assays, GvNR1 displayed very marked nitroreductase activity with several nitro drugs, including metronidazole and other 5-nitroimidazoles. GvNR1 also rendered <em>Escherichia coli</em> BL21-AI much more susceptible to metronidazole when expressed in this strain. In metronidazole-resistant <em>G. vaginalis</em> clinical isolates (&gt;8 µg/mL according to Clinical and Laboratory Standards Institute), GvNR1 was found to be downregulated as well. In resistant clinical strains 33 other proteins were found to be differentially expressed. Of note, these include thioredoxin reductase and vaginolysin. The lowered expression levels of GvNR1 in resistant strains were not caused by mutations in the GvNR1 gene or in sequences directly flanking the gene but by downregulation of mRNA expression. This might explain why <em>G. vaginalis</em> becomes resistant to metronidazole so rapidly.</div></div><div><h3>Conclusions</h3><div>We propose GvNR1 as a novel metronidazole resistance determinant in <em>G. vaginalis</em>.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107681"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668233","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":"Zinc deficiency reverses biofilm azole resistance in Candida albicans","authors":"Yingzhe Wang ,&nbsp;Shigan Ye ,&nbsp;Yuan Deng ,&nbsp;Yingting Huang ,&nbsp;Xiaoliang Zhu","doi":"10.1016/j.ijantimicag.2025.107695","DOIUrl":"10.1016/j.ijantimicag.2025.107695","url":null,"abstract":"<div><h3>Objective</h3><div>Biofilm formation is one of the causes of azole resistance in <em>Candida albicans</em>. Although zinc is an essential trace element involved in biofilm regulation, its specific mechanistic role remains unclear. Here, we systematically evaluated the effects and mechanisms of zinc deficiency on biofilm formation and drug resistance.</div></div><div><h3>Methods</h3><div>Intracellular zinc deficiency was induced using the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and a <em>CSR1</em> knockout strain, as confirmed using zinquin fluorescence. Biofilm formation and susceptibility were assessed using standardized microdilution techniques, including sessile minimum inhibitory concentration (sMIC) determinations via the XTT reduction assay, while drug interactions were assessed using a checkerboard assay. Efflux pump activity was measured using a Rhodamine 6 G assay and transcriptomic analysis was performed to elucidate underlying mechanisms. Pathogenicity was validated using a <em>Galleria mellonella</em> infection model.</div></div><div><h3>Results</h3><div>Zinc deficiency inhibited biofilm development at all stages. Low-concentration TPEN (5 µM) reduced the sessile minimum inhibitory concentration (sMIC) of fluconazole by more than 16-fold and ultimately reversed its azole resistance. This effect was mechanistically associated with the downregulation of key biofilm-related transcription factors and multidrug efflux pumps, as revealed by transcriptomic analysis, which also indicated that zinc deficiency triggered ribosomal remodelling and activated glucose metabolism. Survival analysis in the <em>G. mellonella</em> infection model confirmed that zinc deficiency reduced the overall pathogenicity of <em>C. albicans</em> biofilms.</div></div><div><h3>Conclusions</h3><div>These results validate zinc homeostasis as a novel therapeutic strategy against drug-resistant and recurrent fungal infections, especially those involving biofilms.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107695"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827678","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":"Machine–learning and gene–synergy networks reveal interpretable drivers of antibiotic resistance in Staphylococcus aureus","authors":"Jie Xu ,&nbsp;Yuan Li ,&nbsp;Ying Wang ,&nbsp;Fang Liu ,&nbsp;Jinzhao Long ,&nbsp;Jingyuan Zhu ,&nbsp;Yuefei Jin ,&nbsp;Shuaiyin Chen ,&nbsp;Guangcai Duan ,&nbsp;Haiyan Yang","doi":"10.1016/j.ijantimicag.2025.107690","DOIUrl":"10.1016/j.ijantimicag.2025.107690","url":null,"abstract":"<div><h3>Introduction</h3><div>The evolution of antimicrobial resistance in <em>Staphylococcus aureus</em> (<em>S. aureus</em>) involves complex genotype–phenotype interactions of multiple genetic determinants acting independently.</div></div><div><h3>Objective</h3><div>In this study, we aimed to accurately predict antimicrobial resistance from genomic sequences and uncover the complex genetic interactions underlying its mechanisms, focusing on interpretability and mechanistic insights.</div></div><div><h3>Methods</h3><div>We propose a framework that elucidates antibiotic resistance by linking the genomic context with underlying gene interactions, combining a reference-agnostic gene-context 22-mer (gkmer) representation, a two-step random forest pipeline (RF1 screening/mapping; RF2 gene-level modelling), co-information-based synergy networks, and protein-structure mapping.</div></div><div><h3>Results</h3><div>Using genomic sequences from 4569 <em>S. aureus</em> strains, we successfully predicted resistance to 12 antibiotics and examined the genetic interaction networks for penicillin, ciprofloxacin, and erythromycin in detail. On the held-out 20% test set, RF2 achieved an area under the receiver operating characteristic curve (AUC) of 0.83–1.00 (median 0.90) and an F1 score of 0.58–0.99 (median 0.76); comparable performance was observed for RF1. External validation on an independent dataset including 1011 <em>S. aureus</em> isolates revealed strong generalization for ciprofloxacin, erythromycin, and penicillin (area under the receiver operating characteristic curve &gt; 0.95; F1 &gt; 0.97), while highlighting reduced performance for clindamycin and tetracycline, and failure for gentamicin and trimethoprim, thereby delineating the scope and limits of the model and its applicability. Network analysis revealed distinct structural patterns of gene cooperation, highlighting key hubs and community structures consistent with known resistance pathways.</div></div><div><h3>Conclusions</h3><div>Our findings indicate that antibiotic resistance in <em>S. aureus</em> involves distinct genetic network architectures depending on the antibiotic, highlighting the diverse regulatory pathways bacteria employ to acquire resistance. This discovery-oriented framework prioritizes interpretable determinants and generates testable mechanistic hypotheses, with prospective standardized evaluations aimed at assessing its translatability to clinical settings.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 2","pages":"Article 107690"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742502","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":"Urinary exosome-derived microRNAs as biomarkers of tenofovir disoproxil fumarate (TDF)-induced renal toxicity in people with HIV-1","authors":"José L. Casado ,&nbsp;Pilar Vizcarra ,&nbsp;Francisco J. Hernández-Walias ,&nbsp;José Manuel del Rey ,&nbsp;Carmen Santiuste ,&nbsp;Carmen Molano ,&nbsp;Miriam Menacho ,&nbsp;Alejandro Vallejo","doi":"10.1016/j.ijantimicag.2025.107654","DOIUrl":"10.1016/j.ijantimicag.2025.107654","url":null,"abstract":"<div><h3>Objectives</h3><div>Tenofovir disoproxil fumarate (TDF) has been associated with proximal tubular renal toxicity, though the timing, severity, and long-term outcomes remain controversial. This study aimed to assess urinary exosome-derived microRNAs (miRNAs) as potential early biomarkers of TDF-associated renal toxicity.</div></div><div><h3>Methods</h3><div>In this cross-sectional study of virologically suppressed people with HIV (PWH) on TDF-based therapy (median exposure: 65 months), we isolated urinary exosomes and quantified eight pre-selected miRNAs using real-time qPCR, analysing their associations with tubular function parameters and urinary low-molecular-weight proteins.</div></div><div><h3>Results</h3><div>The 60 selected participants had median TDF exposure of 65 months with mean eGFR-SCr of 90.9 mL/min/1.73m² (6% with chronic kidney disease). Three miRNAs showed significant upregulation with longer TDF exposure: miR-Let-7d (<em>P</em> = 0.049), miR-203 (<em>P</em> = 0.008), and miR-29a (<em>P</em> = 0.02), while miR-127 negatively correlated (<em>P</em> = 0.009). MiR-Let-7d demonstrated strongest associations with tubular dysfunction biomarkers and highest diagnostic value (AUC 0.782; CI, 0.612–0.952). MiR-23a best identified individuals at risk for subsequent eGFR-SCr decline (AUC 0.655; CI, 0.506–0.805) after median 9-month follow-up. Multivariate analysis revealed years living with HIV, miR-Let-7d, and miR-423 were independently associated with tubular dysfunction.</div></div><div><h3>Conclusions</h3><div>Urinary exosome-derived miRNAs demonstrate their potential as early, non-invasive biomarkers for detecting and predicting TDF-associated renal dysfunction in PWH, potentially enabling earlier clinical intervention before irreversible damage occurs.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107654"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426773","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(25)00254-7","DOIUrl":"10.1016/S0924-8579(25)00254-7","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107699"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938327","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":"Molecular mechanisms of resistance and tolerance of Staphylococcus aureus to daptomycin","authors":"Candice Lim ,&nbsp;Geoffrey W. Coombs ,&nbsp;Shakeel Mowlaboccus","doi":"10.1016/j.ijantimicag.2025.107678","DOIUrl":"10.1016/j.ijantimicag.2025.107678","url":null,"abstract":"<div><div>Daptomycin is a cyclic lipopeptide antimicrobial used against gram-positive pathogens, including <em>Staphylococcus aureus</em>. Daptomycin relies on physiological calcium to anchor onto bacterial membranes and sequester lipid II, overproducing reactive oxygen species resulting in cell death. Although daptomycin is thought to be effective against approximately 80% of <em>S. aureus</em>, treatment failure can arise from resistant or tolerant cells. Daptomycin-resistant <em>S. aureus</em> typically acquires mutations in the multiple peptide resistance factor (MprF) to overproduce cationic lysyl-phosphatidylglycerol located on the outer membrane. The increase in positive cell surface charge inhibits daptomycin binding via electrostatic repulsion. Upon exposure to higher daptomycin concentrations, <em>S. aureus</em> may undergo further peptidoglycan modifications to attenuate daptomycin activity. These alterations can also be driven by the crosstalk in the signal transduction systems. Furthermore, the pathways in daptomycin resistance appear to overlap with tolerance which is understudied in <em>S. aureus</em>. In this review, we explore the current understanding of the complex interplay of molecular mechanisms involved in daptomycin resistance and tolerance in <em>S. aureus.</em></div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107678"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145633135","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 TMexCD-TOprJ-producing Vibrio furnissii in retail shellfish","authors":"Haotian Deng ,&nbsp;Zhongpeng Cai ,&nbsp;Kexin Li ,&nbsp;Ludan Xiao ,&nbsp;Yizhang Zheng ,&nbsp;Yihan Chen ,&nbsp;Luchao Lv ,&nbsp;Chao Yue ,&nbsp;Jian-Hua Liu ,&nbsp;Shaowen Li","doi":"10.1016/j.ijantimicag.2025.107680","DOIUrl":"10.1016/j.ijantimicag.2025.107680","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107680"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145633172","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}