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}
{"title":"In reply to the Letter to the Editor regarding ‘Development and Validation of a Time-Varying Correction Factor for QT Interval Assessment in Drug-Resistant Tuberculosis Patients’","authors":"Thanakorn Vongjarudech , Elin Svensson","doi":"10.1016/j.ijantimicag.2025.107539","DOIUrl":"10.1016/j.ijantimicag.2025.107539","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107539"},"PeriodicalIF":4.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086204","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":"The importance of drug exposure in the development of cytomegalovirus resistance","authors":"Katie Lynch, Anne-Grete Märtson","doi":"10.1016/j.ijantimicag.2025.107537","DOIUrl":"10.1016/j.ijantimicag.2025.107537","url":null,"abstract":"<div><h3>Objective</h3><div>Human cytomegalovirus (CMV) is a widespread pathogen which remains asymptomatic in healthy individuals. However, CMV disease can be life-threatening in immunocompromised individuals, particularly in transplant patients. This disease is routinely managed by antiviral agents, including (val)ganciclovir, foscarnet, cidofovir, letermovir, and maribavir. Subtherapeutic antiviral drug exposure is a common occurrence and can lead to drug-resistant CMV development, a key contributor to disease progression. Breakthrough CMV often results in graft loss, end-organ failure, or death. By optimizing intracellular exposure levels of antiviral therapies, it may be possible to improve patient outcomes. Therefore, this review aims to explore the relationship between antiviral exposure and the development of drug-resistant CMV.</div></div><div><h3>Methods</h3><div>A literature search was conducted in Pubmed database including keywords “cytomegalovirus”, “resistance”, “pharmacokinetics”, “pharmacodynamics”, “drug exposure”, “ganciclovir”, “foscarnet”, “maribavir”, “letermovir”, “cidofovir”.</div></div><div><h3>Results</h3><div>There are several challenges to achieving optimal concentrations of current and novel CMV therapies. Narrow therapeutic indices and toxicity profiles of current CMV therapeutics contribute to their subtherapeutic exposure and, hence, suboptimal clinical outcomes. Alternately, novel antivirals such as letermovir and maribavir offer improved pharmacokinetic profiles. However, these agents are associated with rapid resistance development. Overall, a distinct gap exists in understanding the relationship between antiviral exposure and resistance development. As a result, current clinical markers used to predict clinical efficacy lack reliability. In future, resistance development in relation to drug exposure should be included as a clinical trial endpoint to gain understanding of exposure-resistance relationships.</div></div><div><h3>Conclusions</h3><div>With solid knowledge of exposure-resistance relationships, more predictive <em>in vitro</em> and <em>in vivo</em> markers of clinical efficacy can be identified. PK/PD targets that account for free EC50/EC90 and viral load should be defined to improve clinical outcomes and reduce the risk for emergence of R/R CMV.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107537"},"PeriodicalIF":4.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077767","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}