{"title":"A letter to CLSI and EUCAST","authors":"Yan Guo , 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, 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<sub>KPC-2</sub> and C182-ST11-bla<sub>NDM-1</sub>), 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}
Wanessa Santana 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
{"title":"Isopentyl caffeate targets Gp63 (Leishmanolysin) in Leishmania amazonensis","authors":"Wanessa Santana 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":"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 IC<sub>50</sub> of 1.51 µM and a K<em><sub>i</sub></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}
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
{"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":"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> < 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><sub>KPC</sub> and <em>bla</em><sub>IMP</sub> 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 , 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}
{"title":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2025.107543","DOIUrl":"10.1016/j.ijantimicag.2025.107543","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107543"},"PeriodicalIF":4.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147950","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":"Comments on “battle of polymyxin induced nephrotoxicity: Polymyxin B versus colistin”","authors":"Genzhu Wang, Zhongdong Li","doi":"10.1016/j.ijantimicag.2025.107542","DOIUrl":"10.1016/j.ijantimicag.2025.107542","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107542"},"PeriodicalIF":4.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127372","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}
Christen Rune Stensvold , Jeffrey Tomiak , Yohannes Seyoum , Henrik Vedel Nielsen , Mark van der Giezen
{"title":"Letter to the Editor: Comment to ‘Assessment of Dientamoeba fragilis interhuman transmission by faecal microbiota transplantation’ by Moreno-Sabater et al. (2025)","authors":"Christen Rune Stensvold , Jeffrey Tomiak , Yohannes Seyoum , Henrik Vedel Nielsen , Mark van der Giezen","doi":"10.1016/j.ijantimicag.2025.107541","DOIUrl":"10.1016/j.ijantimicag.2025.107541","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107541"},"PeriodicalIF":4.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093605","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}
Deisy Abril , Paola Solorzano , Aura Lucía Leal , Daniela Forero-Hurtado , Oscar Martínez , Luisa F Prada , Mildred Torres , Natasha Vanegas Gómez , Javier Escobar-Perez
{"title":"Ceftazidime/avibactam resistance in Enterobacter cloacae due to the acquisition of a small pHAD28-like plasmid harbouring blaKPC-33","authors":"Deisy Abril , Paola Solorzano , Aura Lucía Leal , Daniela Forero-Hurtado , Oscar Martínez , Luisa F Prada , Mildred Torres , Natasha Vanegas Gómez , Javier Escobar-Perez","doi":"10.1016/j.ijantimicag.2025.107540","DOIUrl":"10.1016/j.ijantimicag.2025.107540","url":null,"abstract":"<div><h3>Objective</h3><div>Ceftazidime/avibactam (CZA) is a β-lactam/β-lactamase inhibitor combination with potent activity against class A β-lactamases of Gram-negative bacilli. In recent years, its use and the emergence of CZA-resistant isolates have increased worldwide, including in Colombia. This study aimed to determine the resistome of a CZA-resistant <em>Enterobacter cloacae</em> isolate and a mobile genetic element related to the <em>bla</em><sub>KPC-33</sub> gene.</div></div><div><h3>Methods</h3><div>The isolate was recovered from a patient with a long hospital stay who had received initial CZA treatment for <em>bla</em><sub>KPC</sub>-positive <em>E. cloacae</em> (CZA-susceptible) bacteraemia. Later, the patient suffered a urinary tract infection where a carbapenem- and CZA-resistant <em>E. cloacae</em> (ST456; ≥256/4 µg/mL) was isolated. The genome of 37Ecl06 was sequenced via NovaSeq (Illumina, San Diego, CA, USA.) and MinION (Oxford Nanopore Technologies, Oxford, UK), antibiotic resistance genes were determined with ResFinder and CARD, and mobile genetic elements identified with PlasmidFinder and ISFinder.</div></div><div><h3>Results</h3><div>Whole-genome sequencing revealed 10 resistance determinants in addition to <em>bla</em><sub>KPC-33</sub>, which was mobilised within the conventional Tn<em>4401b</em> transposon, which in turn appeared to be transposed within a small pHAD28-like plasmid. pHAD28-backbone plasmids have mainly been identified in <em>Salmonella</em> spp. isolates recovered from humans, animals, and food.</div></div><div><h3>Conclusion</h3><div>This is the first report of an <em>E. cloacae</em> isolate harbouring <em>bla</em><sub>KPC-33</sub>. These findings are relevant to continue to understand antimicrobial resistance dissemination mechanisms and to strengthen the One Health approach.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107540"},"PeriodicalIF":4.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093601","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}