International Journal of Antimicrobial Agents最新文献

{"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}

{"title":"Isopentyl caffeate targets Gp63 (Leishmanolysin) in Leishmania amazonensis","authors":"Wanessa Santana Mota ,&nbsp;Simone S.C. Oliveira ,&nbsp;Agenor G. dos Santos-Neto ,&nbsp;Damião P. Souza ,&nbsp;Mayara Castro ,&nbsp;Matheus M. Pereira ,&nbsp;Sona Jain ,&nbsp;Juliana C. Cardoso ,&nbsp;Eliana B. Souto ,&nbsp;Patrícia Severino ,&nbsp;André L.S. Santos","doi":"10.1016/j.ijantimicag.2025.107548","DOIUrl":"10.1016/j.ijantimicag.2025.107548","url":null,"abstract":"<div><h3>Objectives</h3><div>Several drugs are commonly used in the management of Leishmaniasis, but their toxicity, cost, and efficacy depend on the form of the disease.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 <em>Leishmania amazonensis</em> without notable toxicity in a murine model. This study investigated the effects of ICaf on the metallopeptidase gp63 (leishmanolysin), a key virulence factor in <em>Leishmania</em> that supports parasite survival by modulating host immune responses, degrading host proteins, and facilitating macrophage invasion.</div></div><div><h3>Methods and Results</h3><div>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 stabilised through a combination of hydrogen bonding, hydrophobic interactions, metal-acceptor interactions and van der Waals forces. Experimental data supported these <em>in silico</em> findings, with ICaf showing a typical dose-dependent inhibition of gp63 proteolytic activity, resulting in an IC₅₀ of 1.51 µM and a K<em>_i</em> 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.</div></div><div><h3>Conclusions</h3><div>These findings suggest that ICaf is a promising strategy against leishmaniasis, offering a potential new approach to disease treatment.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 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 ,&nbsp;Mei-Chen Tan ,&nbsp;Pei-Jing Chen ,&nbsp;Yih-Ru Shiau ,&nbsp;Hui-Ying Wang ,&nbsp;Jui-Fen Lai ,&nbsp;I-Wen Huang ,&nbsp;Ya-Sung Yang ,&nbsp;Shu-Chen Kuo","doi":"10.1016/j.ijantimicag.2025.107550","DOIUrl":"10.1016/j.ijantimicag.2025.107550","url":null,"abstract":"<div><h3>Objectives</h3><div>The global expansion of antimicrobial-resistant <em>Pseudomonas aeruginosa</em>, 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-<em>P. aeruginosa</em> in Taiwan.</div></div><div><h3>Methods</h3><div>We analysed 503 <em>P. aeruginosa</em> 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.</div></div><div><h3>Results</h3><div>INS-<em>P. aeruginosa</em> 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 remaining susceptible to cefepime-zidebactam. However, the susceptibility rates of INS-<em>P. aeruginosa</em> isolates to other BL-BLIs and comparators declined between 2018 and 2022. Specifically, susceptibility to ceftazidime-avibactam and imipenem-relebactam declined significantly from 81.5% and 85.2% in 2018 to 64.7% and 63.5% in 2022, respectively (both <em>P</em> &lt; 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 <em>bla</em>_KPC and <em>bla</em>_IMP prevalence compared to pre-pandemic data.</div></div><div><h3>Conclusion</h3><div>The COVID-19 pandemic intensified resistance trends in INS-<em>P. aeruginosa</em> in Taiwan, with increasing prevalence and diversity of carbapenemase-encoding genes. Continuous monitoring and expanded research are essential to combat evolving resistance patterns.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 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}

{"title":"Comment on Bayesian evaluation of phage therapy for MDR Acinetobacter Baumannii","authors":"Yuwen Yang ,&nbsp;Rui Lai","doi":"10.1016/j.ijantimicag.2025.107544","DOIUrl":"10.1016/j.ijantimicag.2025.107544","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107544"},"PeriodicalIF":4.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181584","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}