International Journal of Antimicrobial Agents最新文献

{"title":"Efficacy of a bacteriophage cocktail (Arash and Ariobarzanes) in the treatment of Salmonella typhimurium infection in rat model","authors":"Mohammad Hashem Yousefi ,&nbsp;Jeroen Wagemans ,&nbsp;Saeed Nazifi ,&nbsp;Fatemeh Namazi ,&nbsp;Seyed Shahram Shekarforoush ,&nbsp;Saeid Hosseinzadeh","doi":"10.1016/j.ijantimicag.2025.107560","DOIUrl":"10.1016/j.ijantimicag.2025.107560","url":null,"abstract":"<div><h3>Objective</h3><div>The present study exploits <em>Salmonella typhimurium</em>-specific bacteriophages for their application in the treatment of infections caused by <em>S. typhimurium</em> ATCC 14028 in male Sprague-Dawley rats.</div></div><div><h3>Methods</h3><div>A bacteriophage cocktail including two phages, Arash and Ariobarzanes, belonging to the genera <em>Arashvirus</em> and <em>Chivirus</em>, respectively, was administered to rats inoculated with <em>S. typhimurium</em>, and microbiological, haematological, pathological, and immunological parameters were examined.</div></div><div><h3>Results</h3><div>Bacteriophage treatment resulted in a decrease in <em>Salmonella</em> spp. shedding in faeces and their internal organs, as well as at the reduction of the levels of inflammatory cytokines, including tumour necrosis factor alpha and interleukin-8, on different days from d 0 to d 9 post-infection. However, oral gavage of this phage cocktail did not have a significant and visible effect on the improvement of pathological lesions in organs such as the liver and cecum, as well as on haematological and serum biochemical indices.</div></div><div><h3>Conclusions</h3><div>Therefore, a cocktail including phages Arash and Ariobarzanes can at least reduce the <em>S. typhimurium</em> counts in faeces, organs, and inflammatory mediators in rats with Salmonellosis infection.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 4","pages":"Article 107560"},"PeriodicalIF":4.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527839","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":"Rapid detection of cefepime-taniborbactam susceptibility/resistance in Enterobacterales","authors":"Christophe Le Terrier ,&nbsp;Laurent Poirel ,&nbsp;Auriane Kerbol ,&nbsp;Maxime Bouvier ,&nbsp;Patrice Nordmann","doi":"10.1016/j.ijantimicag.2025.107557","DOIUrl":"10.1016/j.ijantimicag.2025.107557","url":null,"abstract":"<div><h3>Objective</h3><div>Metallo-β-lactamase–producing Enterobacterales is widely distributed and confers resistance to all β-lactams, including carbapenems. Recently, a cefepime-taniborbactam combination has been developed that aims to provide a treatment option for infections caused by metallo-β-lactamase–producing bacteria. The objective of this study was to develop a rapid diagnostic test, namely the Rapid Cefepime-Taniborbactam NP test, for the early identification of cefepime-taniborbactam susceptibility or resistance in Enterobacterales.</div></div><div><h3>Methods</h3><div>The Rapid Cefepime-Taniborbactam NP test is based on the detection of glucose metabolism resulting from bacterial growth, detectable by a change in colour of a red phenol (from red to yellow) in the presence of cefepime-taniborbactam. A total of 103 Enterobacterales isolates, including 94 carbapenemase producers, were selected for evaluation of the performance of the Rapid Cefepime-Taniborbactam NP test. In the absence of available breakpoints, two provisional breakpoints were taken for the interpretation—one corresponding to the current Clinical and Laboratory Standards Institute cefepime resistance breakpoint (<em>R</em> ≥ 16 mg/L) and one following current literature on this combination (<em>R</em> ≥ 32 mg/L).</div></div><div><h3>Results</h3><div>The test demonstrated a sensitivity and specificity of 95% and 98%, respectively, following a resistance breakpoint of ≥16 mg/L. When considering a resistance breakpoint of ≥32 mg/L, the sensitivity and specificity were found to be 100% and 91%, respectively. All results were obtained within a 3 h incubation period at 35°C ± 2°C, representing a significant reduction in time compared with current antimicrobial susceptibility testing methods.</div></div><div><h3>Conclusions</h3><div>The results of this study demonstrate that the Rapid Cefepime-Taniborbactam NP test is a highly accurate and time-efficient technique for the detection of bacterial resistance.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 4","pages":"Article 107557"},"PeriodicalIF":4.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368846","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 the editor regarding “Bayesian evaluation of phage therapy efficacy against multidrug-resistant Acinetobacter Baumannii”","authors":"Momna Arooj Malik ,&nbsp;Sobia Manzoor ,&nbsp;Javed Ashraf","doi":"10.1016/j.ijantimicag.2025.107555","DOIUrl":"10.1016/j.ijantimicag.2025.107555","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 4","pages":"Article 107555"},"PeriodicalIF":4.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368844","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":"No one-size-fits-all approach: Retrospective analysis of efficacy and safety of serum concentrations of continuously administered vancomycin in critically ill adults reveals different target serum concentrations depending on disease severity","authors":"Katrin Viertel ,&nbsp;Carmen van Meegen ,&nbsp;Thorsten Annecke ,&nbsp;Swetlana Herbrandt ,&nbsp;Frauke Mattner","doi":"10.1016/j.ijantimicag.2025.107556","DOIUrl":"10.1016/j.ijantimicag.2025.107556","url":null,"abstract":"<div><h3>Background</h3><div>Vancomycin is frequently monitored, but target levels for continuous infusion of vancomycin (CIV) are based on expert opinion. Rarely have vancomycin concentrations been correlated with therapeutic efficacy or safety of CIV.</div></div><div><h3>Objectives</h3><div>Associations between vancomycin steady-state serum concentrations and treatment failure or toxicity with CIV were examined.</div></div><div><h3>Methods</h3><div>A retrospective, single-centre cohort study was conducted of consecutive critically ill surgical patients receiving CIV between 2010 and 2022. After detecting associations between vancomycin levels, renal function and health status, four subgroups were defined based on estimated glomerular filtration rate (&lt;/≥90 mL/min/1.73m²) and Simplified Acute Physiology Score (SAPS) II (≤/&gt;36). Failure and toxicity of vancomycin serum concentrations were assessed using primary (mortality, acute kidney injury (AKI)) and secondary (clinical and microbiological failure) endpoints. Predictors of outcome parameters were identified using logistic and Cox regression. Concentrations were compared by bivariate comparisons, post-hoc tests following analysis of variance for the regression models and desirability of outcome ranking. Concentration cut-offs were determined by receiver-operating characteristic and classification and regression tree analyses.</div></div><div><h3>Results</h3><div>922 patients were included. Higher vancomycin concentrations (first 72 h average, specifically &gt;25 mg/L) were associated with higher mortality, AKI and clinical failure, but less microbiological failure. For SAPS&gt;36, concentrations &lt;20 mg/L (i.e. 15–20 mg/L or &lt;17 mg/L) correlated with the best treatment outcome, for SAPS≤36 concentrations &gt;19 mg/L (i.e. 20–25 mg/L or 19–28 mg/L).</div></div><div><h3>Conclusion</h3><div>Retrospective analyses of vancomycin serum concentrations during CIV suggest that ICU patients’ disease severity should be considered when selecting a target concentration. The target concentration might be sought inversely related to SAPS, which should be confirmed in future prospective controlled trials.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 4","pages":"Article 107556"},"PeriodicalIF":4.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368845","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":"Within-host resistance evolution of ST15 Klebsiella pneumoniae in an ICU immunosuppressed patient under antibiotic pressure of polymyxins, ceftazidime-avibactam, and meropenem","authors":"Bin Tang ,&nbsp;Tianjiao Meng ,&nbsp;Lijun Tian ,&nbsp;Ming Zhong ,&nbsp;Yunqi Dai ,&nbsp;Rui Tian ,&nbsp;Tingting Pan ,&nbsp;Jingyong Sun ,&nbsp;Ruoming Tan ,&nbsp;Xiaoli Wang ,&nbsp;Hongping Qu","doi":"10.1016/j.ijantimicag.2025.107554","DOIUrl":"10.1016/j.ijantimicag.2025.107554","url":null,"abstract":"<div><h3>Objectives</h3><div>Carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) is a major pathogen in healthcare-associated infections, posing a severe and potentially fatal threat to critically ill patients. This study aims to investigate the evolution of antimicrobial resistance under the selective pressure from multiple antibiotics in immunocompromised patients in intensive care unit (ICU).</div></div><div><h3>Methods</h3><div>In this study, we report the complex dynamic evolution of resistance in ST15 CRKP in an immunocompromised critically ill patient, driven by adjustments in antibiotic regimens involving polymyxin, ceftazidime-avibactam (CZA), and meropenem. Antimicrobial susceptibility testing, whole-genome sequencing, and mutation analysis were performed on longitudinal clinical isolates.</div></div><div><h3>Results</h3><div>We identified polymyxin resistance associated with mutations, such as in <em>mgrB</em>, and polymyxin heteroresistance, which was detected prior to antibiotic exposure and expanded to full resistance under selective pressure. Additionally, we identified three KPC variants responsible for CZA resistance in a single patient, including a novel <em>bla</em>_KPC-151 variant. The novel KPC-151 enzyme features a deletion of tyrosine (Y) at position 241 to threonine (T) at position 243, with a substitution of serine (S). Cloning experiments and enzyme kinetic measurements confirmed that KPC-151 confers resistance to ceftazidime-avibactam while restoring susceptibility to carbapenems. All KPC variants originated from a mobile genetic element flanked by IS<em>26,</em> IS<em>26-</em>IS<em>Kpn27-bla</em>_KPC-2<em>/</em>variants<em>-</em>IS<em>Kpn6-</em>Tn<em>As1-</em>IS<em>26</em>, demonstrating its high potential to drive KPC mutations.</div></div><div><h3>Conclusions</h3><div>This study underscores the rapid and diverse evolutionary adaptability of <em>K. pneumoniae</em> under multiple antibiotic pressures in immunocompromised critically ill patients, emphasizing the need for dynamic monitoring of antimicrobial susceptibility testing and resistance gene mutations to guide antibiotic adjustments.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 4","pages":"Article 107554"},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340094","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 susceptibility to new antibiotics and genetic characterisation of carbapenemase-producing Enterobacterales: Low activity of cefiderocol against NDM-producing isolates","authors":"Lisa Faxén ,&nbsp;Vilhelm Müller ,&nbsp;Margarita Chatzopoulou ,&nbsp;Oskar Karlsson Lindsjö ,&nbsp;Pernilla Lagerbäck ,&nbsp;Karin Westmo ,&nbsp;Anna Åkerlund ,&nbsp;Thomas Tängdén ,&nbsp;Inga Fröding","doi":"10.1016/j.ijantimicag.2025.107553","DOIUrl":"10.1016/j.ijantimicag.2025.107553","url":null,"abstract":"<div><h3>Objectives</h3><div>Carbapenemase-producing Enterobacterales (CPEs) pose a serious medical threat. In recent years, several new antibiotics targeting carbapenem-resistant Gram-negative bacteria have been introduced, including cefiderocol, ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam. However, no systematic monitoring of susceptibility levels is routinely performed, which challenges rational use and the effectiveness of the new antibiotics due to the risk of rapid emergence of resistance. The objective of this study was to assess the susceptibility of new antibiotics targeting carbapenem-resistant Gram-negative bacteria against CPEs in Sweden.</div></div><div><h3>Methods</h3><div>All CPE isolates collected through Sweden's national microbial surveillance programme in 2022 were included. Susceptibility testing for the new antibiotics and other agents relevant to CPEs was performed with broth microdilution for all drugs except for cefiderocol and fosfomycin, for which EUCAST disk diffusion was applied. Whole-genome sequencing was performed for genetic characterisation.</div></div><div><h3>Results</h3><div>In total, 286 CPEs were included in the study. Susceptibility rates were high for ceftazidime-avibactam in OXA-48-like producing isolates (n = 116, &gt;95%) and for ceftazidime-avibactam and meropenem-vaborbactam against KPC/IMI-producing isolates (n = 22, ≥90%). In contrast, susceptibility to cefiderocol was low in MBL-producing Enterobacterales according to disk diffusion: 0% (0/76) of <em>Escherichia coli</em> and 6% (3/54) of <em>Klebsiella pneumoniae</em> were classified susceptible, and 93% (71/76) and 39% (21/54), respectively, were resistant. The presence of <em>bla</em>_NDM-5 was associated with the highest level of resistance.</div></div><div><h3>Conclusions</h3><div>Considerable variability was observed in the susceptibility rates of the newly introduced antibiotics against CPEs collected in Sweden. Continued surveillance is warranted to guide rational use of these new last-resort antibiotics.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 4","pages":"Article 107553"},"PeriodicalIF":4.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484294","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 vitro activity of cefepime/enmetazobactam against Klebsiella pneumoniae carrying blaKPC allelic variants conferring resistance to ceftazidime/avibactam","authors":"Luca Caiazzo ,&nbsp;Edoardo Carretto ,&nbsp;Paolo Gaibani","doi":"10.1016/j.ijantimicag.2025.107552","DOIUrl":"10.1016/j.ijantimicag.2025.107552","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107552"},"PeriodicalIF":4.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283845","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":"A letter to CLSI and EUCAST","authors":"Yan Guo ,&nbsp;Fupin Hu","doi":"10.1016/j.ijantimicag.2025.107549","DOIUrl":"10.1016/j.ijantimicag.2025.107549","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 4","pages":"Article 107549"},"PeriodicalIF":4.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274783","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":"Elucidating adaptive compensatory tigecycline resistance mechanisms of RamA, RarA and SoxS in Klebsiella pneumoniae","authors":"Junyang Kuai ,&nbsp;Yifan Zhao ,&nbsp;Ruobing Wang ,&nbsp;Yawei Zhang ,&nbsp;Henan Li ,&nbsp;Hongbin Chen ,&nbsp;Xiaojuan Wang ,&nbsp;Hui Wang","doi":"10.1016/j.ijantimicag.2025.107551","DOIUrl":"10.1016/j.ijantimicag.2025.107551","url":null,"abstract":"<div><h3>Background</h3><div>The molecular regulation of tigecycline resistance is complex, and the roles of RamA, RarA, and SoxS regulons in tigecycline resistance are not fully understood.</div></div><div><h3>Methods</h3><div>Carbapenem-resistant (C248-ST11-<em>bla</em>KPC-2 and C182-ST11-<em>bla</em>_NDM-1), colistin-resistant (HK1-ST562-<em>mcr</em>-1), and tigecycline-resistant (KP17) strains with single or double regulon gene knockouts were evolved <em>in vitro</em> to generate tigecycline-resistant mutants. CRISPR-Cas9 was used to create KP17 mutants lacking <em>rarA, ramA, lon</em>, or their combinations. The mutant prevention concentration (MPC) of tigecycline and mutation frequency of regulon mutants were assessed. Phenotypic differences between the mutants and parents were assessed using growth curves, <em>in vitro</em> competition growth, serum bactericidal activity, biofilm formation, and hydrogen peroxide resistance tests. Genetic and transcriptomic variations were analyzed using whole-genome and RNA sequencing.</div></div><div><h3>Results</h3><div>Acquired high-level tigecycline resistance in carbapenem-and colistin-resistant strains incurred fitness costs and reduced virulence. Colistin-resistant strains rapidly evolved high-level tigecycline resistance, with minimum inhibitory concentration of up to 256 mg/L. The RamRA-AcrAB/OqxAB pathway was pivotal for tigecycline resistance in carbapenem- and colistin resistant strains. Lon was not related to tigecycline resistance but appeared to be linked to oxidative stress. Although knocking out the key regulon genes RamA and/or RarA did not impede tigecycline resistance development, these knockouts influenced mutation frequencies and MPCs, with RarA knockout increasing the number of mutation sites.</div></div><div><h3>Conclusion</h3><div>RarA and SoxS served as compensatory regulons in the absence of RamA, or in double knockouts. These findings improved our understanding of the mechanisms underlying tigecycline resistance in <em>K. pneumoniae</em>.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 4","pages":"Article 107551"},"PeriodicalIF":4.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274784","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)00102-5","DOIUrl":"10.1016/S0924-8579(25)00102-5","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107545"},"PeriodicalIF":4.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221035","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}