International Journal of Antimicrobial Agents最新文献

{"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, Sobia Manzoor, Javed Ashraf","doi":"10.1016/j.ijantimicag.2025.107555","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107555","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"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":"Rapid detection of cefepime-taniborbactam susceptibility/resistance in Enterobacterales.","authors":"Christophe LE Terrier, Laurent Poirel, Auriane Kerbol, Maxime Bouvier, Patrice Nordmann","doi":"10.1016/j.ijantimicag.2025.107557","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107557","url":null,"abstract":"<p><p>Metallo-β-lactamases (MBL) producing-Enterobacterales are widely distributed and confer resistance to all β-lactams, including carbapenems. Recently, the cefepime-taniborbactam combination has been developed and is aimed to constitute a treatment option for infections caused by MBL-producing bacteria. The objective of this study was to develop a rapid diagnostic test, namely the Rapid Cefepime-Taniborbactam NP, for the early identification of Cefepime-Taniborbactam susceptibility/resistance in Enterobacterales. The Rapid Cefepime-Taniborbactam NP test is based on the detection of glucose metabolisation resulting from bacterial growth, and detectable by a color change of 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 Cefepime-Taniborbactam NP test. In the absence of available breakpoints, two provisional breakpoints were taken for the interpretation, one corresponding to the current cefepime resistance breakpoint of CLSI (R ≥ 16 mg/L) and one following current literature on this combination (R ≥ 32 mg/L). 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 three-hour incubation period at 35°C ± 2°C, representing a significant reduction in time compared to current antimicrobial susceptibility testing methods. The results of this study demonstrated that the Rapid Cefepime-Taniborbactam NP test is a highly accurate and time-efficient technique for the detection of bacterial resistance.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"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":"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, Carmen van Meegen, Thorsten Annecke, Swetlana Herbrandt, Frauke Mattner","doi":"10.1016/j.ijantimicag.2025.107556","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107556","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>Associations between vancomycin steady-state serum concentrations and treatment failure or toxicity with CIV were examined.</p><p><strong>Methods: </strong>A retrospective, single-centre cohort study was conducted of consecutive critically ill surgical patients receiving CIV between 2010-2022. After detecting associations between vancomycin levels, renal function and health status, four subgroups were defined based on estimated glomerular filtration rate (</≥90mL/min/1.73m²) and Simplified Acute Physiology Score (SAPS) II (≤/>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.</p><p><strong>Results: </strong>922 patients were included. Higher vancomycin concentrations (first 72h average; specifically >25mg/L) were associated with higher mortality, AKI and clinical failure, but less microbiological failure. For SAPS>36, concentrations <20mg/L (i.e. 15-20mg/L or <17mg/L) correlated with the best treatment outcome, for SAPS≤36 concentrations >19mg/L (i.e. 20-25mg/L or 19-28mg/L).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"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, Tianjiao Meng, Lijun Tian, Ming Zhong, Yunqi Dai, Rui Tian, Tingting Pan, Jingyong Sun, Ruoming Tan, Xiaoli Wang, Hongping Qu","doi":"10.1016/j.ijantimicag.2025.107554","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107554","url":null,"abstract":"<p><p>Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major pathogen in healthcare-associated infections, posing a severe and potentially fatal threat to critically ill patients. Immunocompromised patients in intensive care units (ICUs) are subjected to selective pressure from multiple antibiotics, which can lead to further resistance evolution. 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. Through antimicrobial susceptibility testing, whole-genome sequencing, and mutation analysis of longitudinal clinical isolates, we identified polymyxin resistance associated with mutations, such as in mgrB, 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 bla_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 IS26, IS26-ISKpn27-bla_KPC-2/variants-ISKpn6-TnAs1-IS26, demonstrating its high potential to drive KPC mutations. This study underscores the rapid and diverse evolutionary adaptability of K. pneumoniae 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.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"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":"In vitro activity of Cefepime/Enmetazobactam against Klebsiella pneumoniae carrying bla_KPC allelic variants conferring resistance to Ceftazidime/Avibactam.","authors":"Luca Caiazzo, Edoardo Carretto, Paolo Gaibani","doi":"10.1016/j.ijantimicag.2025.107552","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107552","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"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, Fupin Hu","doi":"10.1016/j.ijantimicag.2025.107549","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107549","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"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, Yifan Zhao, Ruobing Wang, Yawei Zhang, Henan Li, Hongbin Chen, Hui Wang, Xiaojuan Wang","doi":"10.1016/j.ijantimicag.2025.107551","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107551","url":null,"abstract":"<p><p>To investigate the roles of RamA, RarA, and SoxS regulators in tigecycline resistance in Klebsiella pneumoniae, carbapenem-resistant (C248-ST11-bla_KPC-2 and C182-ST11-bla_NDM-1), colistin-resistant (HK1-ST562-mcr-1), and tigecycline-resistant (KP17) strains with single or double regulon gene knockouts were evolved in vitro to generate tigecycline-resistant mutants. CRISPR-Cas9 was used to create KP17 mutants lacking rarA, ramA, lon, 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, in vitro competition growth, serum bactericidal activity, biofilm formation, and hydrogen peroxide resistance tests. Genetic and transcriptomic variations were analyzed using whole-genome and RNA sequencing. Adaptive compensatory mechanisms of RamA, RarA, and SoxS in tigecycline resistance of K. pneumoniae were investigated. 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. 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 K. pneumoniae.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"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}

{"title":"Isopentyl Caffeate Targets Gp63 (Leishmanolysin) in Leishmania amazonensis.","authors":"Wanessa S Mota, Simone S C Oliveira, Agenor G Dos Santos-Neto, Damião P Souza, Mayara Castro, Matheus M Pereira, Sona Jain, Juliana C Cardoso, Eliana B Souto, Patrícia Severino, André L S Santos","doi":"10.1016/j.ijantimicag.2025.107548","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107548","url":null,"abstract":"<p><p>Leishmaniasis is managed with a variety of compounds, whose toxicity, cost, and efficacy vary depending on the disease form. Nevertheless, the development of new therapeutics remains important to expand treatment options and address existing limitations. Previously, we reported that isopentyl caffeate (ICaf) exhibited potent activity against promastigotes and amastigotes of Leishmania amazonensis without notable toxicity in a murine model. This study investigated the effects of ICaf on the metallopeptidase gp63 (leishmanolysin), a key virulence factor in Leishmania that supports parasite survival by modulating host immune responses, degrading host proteins, and facilitating macrophage invasion. Molecular docking analysis revealed that ICaf interacted with key amino acids within the active site of gp63, achieving a docking score of -5.5 kcal/mol. The gp63-ICaf interaction was stabilized through a combination of hydrogen bonding, hydrophobic interactions, metal-acceptor interactions and van der Waals forces. Experimental data supported these in silico findings, with ICaf showing a typical dose-dependent inhibition of gp63 proteolytic activity, resulting in an IC₅₀ of 1.51 µM and a K_i of 9.89 µM. The formation of a stable gp63-ICaf complex was demonstrated by gel electrophoresis assay. Furthermore, pretreatment of promastigotes with ICaf reduced cell-associated gp63 proteolytic activity, as evidenced by decreased hydrolysis of the fluorogenic peptide substrate Z-Phe-Arg-AMC and gelatin incorporated into electrophoresis gel. Flow cytometry and confocal microscopy, both using anti-gp63 antibodies, further confirmed a decrease in gp63 expression on the parasite surface. In summary, these findings suggest that ICaf is a promising strategy against leishmaniasis, offering a potential new approach to disease treatment.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107548"},"PeriodicalIF":4.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247755","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-zidebactam, ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, and other comparators against imipenem-non-susceptible Pseudomonas aeruginosa in Taiwan, 2022.","authors":"Yu-Lin Lee, Mei-Chen Tan, Pei-Jing Chen, Yih-Ru Shiau, Hui-Ying Wang, Jui-Fen Lai, I-Wen Huang, Ya-Sung Yang, Shu-Chen Kuo","doi":"10.1016/j.ijantimicag.2025.107550","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107550","url":null,"abstract":"<p><strong>Objectives: </strong>The global expansion of antimicrobial-resistant Pseudomonas aeruginosa, particularly imipenem-non-susceptible (INS) strains poses a formidable health threat. The COVID-19 pandemic has exacerbated antimicrobial resistance trends. We compared the pre- and post-pandemic antibiotic resistance patterns of INS-P. aeruginosa in Taiwan.</p><p><strong>Methods: </strong>We analyzed 503 P. aeruginosa isolates collected through the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program during 2022. Minimum inhibitory concentrations of various antibiotics were determined by using broth microdilution. Carbapenemase-encoding genes were identified via multiplex PCR. Antimicrobial resistance trends were compared with data from 2018.</p><p><strong>Results: </strong>INS-P. aeruginosa comprised 16.9% (85/503) of isolates and exhibited high-level multi-drug resistance. Novel β-lactam-β-lactamase inhibitor combinations (BL-BLIs) demonstrated the highest activity, with 89.4% of INS isolates susceptible to cefepime-zidebactam. The susceptibility rates of INS-P. aeruginosa isolates to other BL-BLIs and comparators declined between 2018 and 2022. Specifically, susceptibility to ceftazidime-avibactam and imipenem-relebactam decreased from 81.5% and 85.2% during 2018 to 64.7% and 63.5% during 2022, respectively (both p<0.05). Additionally, only 70.6% of isolates obtained during 2022 were susceptible to ceftolozane-tazobactam. Carbapenemase genes were detected in 10.6% of isolates, with a notable increase in bla_KPC and bla_IMP prevalence compared to pre-pandemic data.</p><p><strong>Conclusion: </strong>The COVID-19 pandemic intensified resistance trends in INS-P. aeruginosa in Taiwan, with increasing prevalence and diversity of carbapenemase-encoding genes. Continuous monitoring and expanded research are essential to combat evolving resistance patterns.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107550"},"PeriodicalIF":4.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247754","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}