Caroline Othilie Dedekam Pederssen, Son Lam Pham, Paula Žugec, Jan Homolak, Ivana Šutej, Roger Junges
{"title":"The impact of medical and dental education on student antimicrobial resistance literacy in Croatia.","authors":"Caroline Othilie Dedekam Pederssen, Son Lam Pham, Paula Žugec, Jan Homolak, Ivana Šutej, Roger Junges","doi":"10.1093/jacamr/dlag183","DOIUrl":"10.1093/jacamr/dlag183","url":null,"abstract":"<p><strong>Background and objectives: </strong>Antimicrobial resistance is a pressing public health concern in Croatia, where antibiotic consumption exceeds the European average. Assessing the impact of education on antimicrobial resistance literacy among future prescribers is a priority, yet parallel evidence from both medicine and dentistry remains limited. Here we evaluated the effect of curriculum-based education on antimicrobial resistance literacy among Croatian medical and dental students across all study years.</p><p><strong>Methods: </strong>We used a cross-sectional survey to assess dental and medical students' attitudes towards antibiotics and antimicrobial resistance. Domains included perceptions, knowledge, confidence to prescribe and educational interest. Descriptive statistics were used coupled with statistical testing for comparison across study years.</p><p><strong>Results: </strong>A total of 692 responses were collected. Antimicrobial resistance was selected as one of the top global priorities by both medical and dental students. While AMR was broadly recognized as a global challenge, significant knowledge gains across study years were more pronounced in dental than in medical students, particularly from year 1 to subsequent years. Over 58% of final-year medical students reported feeling patient-imposed pressure to prescribe antibiotics. For fifth- and sixth-year students, a marked difference in patient communication was observed as >60% of medical students reported discussing antimicrobial resistance with patients very often, compared with only 10% of dental students.</p><p><strong>Conclusions: </strong>We showed a positive effect of education throughout the study years in both medicine and dentistry, with more evident effects in the latter. High reported pressures to prescribe coupled with a gap in communication practices were observed.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 4","pages":"dlag183"},"PeriodicalIF":3.9,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mikiyas G Teferi, Kebron W Aweke, Gelila S Kassa, Selamawit Z Tadesse, Elias Gashaw Endegnanew, Eden Haile Hagos, Biruk T Mengistie, Chernet T Mengistie, Demmelash Gezahegn Nigatu, Eskedar Ferdu Azerefegne
{"title":"Online education resources for antimicrobial stewardship in Ethiopia: an educational resource review.","authors":"Mikiyas G Teferi, Kebron W Aweke, Gelila S Kassa, Selamawit Z Tadesse, Elias Gashaw Endegnanew, Eden Haile Hagos, Biruk T Mengistie, Chernet T Mengistie, Demmelash Gezahegn Nigatu, Eskedar Ferdu Azerefegne","doi":"10.1093/jacamr/dlag193","DOIUrl":"10.1093/jacamr/dlag193","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial stewardship (AMS) in Ethiopia requires practical and scalable educational resources that can support healthcare workers in resource-limited settings. Online resources may help strengthen stewardship knowledge and implementation, but their value depends on accessibility, contextual relevance and practical utility.</p><p><strong>Objectives: </strong>To identify and appraise online AMS educational resources relevant to Ethiopia and to assess their potential contribution to AMS education and implementation.</p><p><strong>Methods: </strong>We conducted a targeted education resource review of six publicly accessible online AMS resources. Targeted searches combined antimicrobial stewardship (AMS) and antimicrobial resistance (AMR) education terms with Ethiopia, low- and middle-income country settings, toolkit, training, online course, massive open online course (MOOC), OpenWHO, FutureLearn, CDC, BSAC and WHO. Resources were evaluated for accessibility, educational design, contextual appropriateness, implementation utility and complementarity.</p><p><strong>Results: </strong>The Ethiopian national practical guide had the strongest implementation relevance because of its close alignment with local stewardship priorities and facility-level needs. WHO- and course-based resources added structured learning and broader programmatic support. Across resources, common limitations included dependence on internet connectivity, limited offline usability and insufficient locally contextualized case-based learning.</p><p><strong>Conclusions: </strong>The included resources offer complementary value for AMS education in Ethiopia, but no single resource is sufficient on its own. A blended, context-adapted approach that integrates national guidance with selected online educational resources is likely to provide the greatest educational and system-level benefit.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 4","pages":"dlag193"},"PeriodicalIF":3.9,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liujing Miao, Xingyun Hou, Yuzhu Wang, Chengchun Zuo, Jie Li, Qianzhou Lv, Xiaoyu Li, Kunming Pan
{"title":"Vancomycin-associated acute kidney injury in patients with moderate CKD: a multicentre retrospective cohort study.","authors":"Liujing Miao, Xingyun Hou, Yuzhu Wang, Chengchun Zuo, Jie Li, Qianzhou Lv, Xiaoyu Li, Kunming Pan","doi":"10.1093/jacamr/dlag173","DOIUrl":"10.1093/jacamr/dlag173","url":null,"abstract":"<p><strong>Background: </strong>Vancomycin, as a first-line treatment for methicillin-resistant staphylococcus aureus infections, is notably nephrotoxic. Research on vancomycin nephrotoxicity in patients with moderate chronic kidney disease (CKD) is still lacking. This study aims to investigate the incidence of vancomycin-associated acute kidney injury (VA-AKI) in patients with moderate CKD and to identify associated risk factors in this specific population.</p><p><strong>Methods: </strong>This was a multicentre, retrospective, cohort study from China. Patients with estimated glomerular filtration rate (eGFR) ˂90 mL/(min·1.73 m<sup>2</sup>) who received vancomycin from January 2009 to December 2024 were included. For patients with moderate CKD and eGFR ˂60 mL/(min·1.73 m<sup>2</sup>), multivariate logistic regression analysis was used to identify the independent risk factors for VA-AKI and the prognosis of VA-AKI patients.</p><p><strong>Results: </strong>A total of 3844 patients were included, and 1194 patients had moderate CKD. The incidence of VA-AKI in patients with moderate CKD was 19.1% (228/1194). The risk of VA-AKI increased significantly with the progression of CKD stages (<i>P</i> = 0.003). Cardiac insufficiency (OR 1.816, 95% CI 1.320-2.500, <i>P</i> < 0.001), ICU admission (OR 2.018, 95% CI 1.449-2.810, <i>P</i> < 0.001), and duration of vancomycin therapy (OR 1.482, 95% CI 1.071-2.051, <i>P</i> = 0.018) were significantly and independently associated with VA-AKI in patients with moderate CKD.</p><p><strong>Conclusions: </strong>The incidence of VA-AKI in patients with moderate CKD is slightly higher than that in mixed populations (general, unselected hospitalized cohorts). This study indicates that the risk of VA-AKI increases with the severity of CKD staging. Heart failure, ICU admission, and duration of vancomycin therapy may result in a higher risk of VA-AKI occurrence.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 4","pages":"dlag173"},"PeriodicalIF":3.9,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pattarachai Kiratisin, Alona Kuraieva, Eric Utt, Susanna Esposito
{"title":"<i>In vitro</i> activity of ceftaroline against clinical isolates of Gram-positive bacteria in paediatric patients: ATLAS programme 2018-2023.","authors":"Pattarachai Kiratisin, Alona Kuraieva, Eric Utt, Susanna Esposito","doi":"10.1093/jacamr/dlag179","DOIUrl":"10.1093/jacamr/dlag179","url":null,"abstract":"<p><strong>Objectives: </strong>This study evaluated the antimicrobial activity of ceftaroline and comparator antimicrobials against clinical isolates of Gram-positive bacteria (GPB) from paediatric patients globally and in Africa/Middle East (AfME), Asia-Pacific (APAC), Europe and Latin America (LATAM) as part of the Antimicrobial Testing Leadership and Surveillance programme between 2018 and 2023.</p><p><strong>Methods: </strong>Susceptibility and minimum inhibitory concentrations of all organisms were determined using broth microdilution methodology for ceftaroline and comparators from Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints.</p><p><strong>Results: </strong>Overall and across regions, <i>Staphylococcus aureus</i> (CLSI/EUCAST, ≥99.0%) and methicillin-resistant <i>S. aureus</i> (CLSI, ≥95.6%) demonstrated high susceptibility to ceftaroline. High susceptibility to daptomycin, linezolid, teicoplanin, tigecycline (from the FDA), trimethoprim/sulfamethoxazole and vancomycin was demonstrated against these isolates for both breakpoints. Globally and across regions, for <i>Streptococcus pneumoniae</i> (CLSI/EUCAST, 93.3%-100%) and penicillin-intermediate <i>S. pneumoniae</i> (CLSI/EUCAST, 100%), high susceptibility to ceftaroline was observed. For penicillin-resistant <i>S. pneumoniae</i>, higher susceptibility to ceftaroline following the CLSI (96.5%-100%) than EUCAST (74.4%-88.7%) was observed except in LATAM. High susceptibility to linezolid, levofloxacin, tigecycline and vancomycin was demonstrated against these isolates across regions from both breakpoints, whereas, for ceftriaxone, higher susceptibility following the CLSI than EUCAST was observed. For β-haemolytic streptococci, high susceptibility to ceftaroline was observed (CLSI, 100%). High susceptibility to linezolid, penicillin and vancomycin was demonstrated against these isolates from both breakpoints.</p><p><strong>Conclusions: </strong>Ceftaroline demonstrated potent activity against key GPB. This study significantly contributes to the limited current information on paediatric antimicrobial resistance patterns across AfME, APAC, Europe and LATAM.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 4","pages":"dlag179"},"PeriodicalIF":3.9,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rachel J Grainger, Niall T Stevens, Hilary Humphreys, Fidelma Fitzpatrick
{"title":"Comment on: Exploring UK medical schools' perception and intent for teaching on antimicrobial resistance and stewardship.","authors":"Rachel J Grainger, Niall T Stevens, Hilary Humphreys, Fidelma Fitzpatrick","doi":"10.1093/jacamr/dlag187","DOIUrl":"10.1093/jacamr/dlag187","url":null,"abstract":"","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 4","pages":"dlag187"},"PeriodicalIF":3.9,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clara Tam, Gill Boothman, Alison Hughes, Neil Powell
{"title":"Exploring spurious penicillin allergy prevalence in general practices in North Wales.","authors":"Clara Tam, Gill Boothman, Alison Hughes, Neil Powell","doi":"10.1093/jacamr/dlag190","DOIUrl":"10.1093/jacamr/dlag190","url":null,"abstract":"","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 4","pages":"dlag190"},"PeriodicalIF":3.9,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Helena Ferreira Leal, Fazia Tadount, Jie He, Élise Fortin, Françoise Bichai, Caroline Quach, Emilie Bédard
{"title":"Mapping antimicrobial resistance awareness in Canada: what are our knowledge gaps?","authors":"Helena Ferreira Leal, Fazia Tadount, Jie He, Élise Fortin, Françoise Bichai, Caroline Quach, Emilie Bédard","doi":"10.1093/jacamr/dlag162","DOIUrl":"10.1093/jacamr/dlag162","url":null,"abstract":"<p><strong>Background: </strong>Often referred to as a silent pandemic, antimicrobial resistance (AMR) is gradually expanding worldwide. Addressing this escalating threat requires collaborative efforts from governments, stakeholders and community members; thus, fostering widespread public knowledge is crucial. We aimed to assess the knowledge, attitudes and practices (KAPs) related to AMR in a diverse cohort from the province of Quebec, Canada, to identify critical gaps in targeted educational interventions.</p><p><strong>Methods: </strong>An observational, cross-sectional, descriptive study was conducted from April 2022 to August 2023. Participants included individuals 18 years or older from urban areas in Quebec, focusing on the cities of Montreal and Laval. The data were collected using a questionnaire adapted from the World Health Organization's 'Antibiotic Resistance: Multi-country Public Awareness Survey'.</p><p><strong>Results: </strong>The study engaged 1774 participants and revealed a fair understanding of AMR, with misconception rates varying from 9.9% to 58.3%. However, significant knowledge gaps were identified. When asked about following the recommended length of treatment and daily dosage of antibiotics, 13.8% affirmed not fully adhering. When asked if medication was stopped once symptoms started to disappear, 7.3% responded 'always' and 20.4% 'sometimes'. Additionally, 12.5% reported taking oral antibiotics without a prescription. Notably, men, younger audiences (18-34) and individuals with lower formal education were more prone to risky AMR-related behaviours.</p><p><strong>Conclusions: </strong>This study reveals significant gaps in public understanding and practices related to AMR in Quebec. Enhanced public education campaigns, stricter antimicrobial use regulations and tailored educational programmes targeting high-risk groups are recommended. An improved understanding of AMR can significantly contribute to global efforts to combat this pressing health issue.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 4","pages":"dlag162"},"PeriodicalIF":3.9,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13511133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atiyeh Asadpour, Richa Sharma, Jana Suklan, Stephen P Kidd, Julie Hart, Alexander Daniel Edwards, Sarah Helen Needs
{"title":"The evidence landscape for direct-from-urine antibiotic susceptibility testing (AST) for urinary tract infection (UTI): a scoping review.","authors":"Atiyeh Asadpour, Richa Sharma, Jana Suklan, Stephen P Kidd, Julie Hart, Alexander Daniel Edwards, Sarah Helen Needs","doi":"10.1093/jacamr/dlag170","DOIUrl":"10.1093/jacamr/dlag170","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial susceptibility tests (AST) are vital to guide antibiotic selection to treat bacterial infections, including urinary tract infections (UTI). Current laboratory AST takes at least 2 days. Direct testing of urine samples could speed up testing, with rapid reporting aiding timely treatment.</p><p><strong>Method: </strong>A scoping review was conducted to identify studies assessing the accuracy of direct-from-urine AST, and map the breadth of evidence. Studies that measured overall categorical agreement (CA) compared to a reference method were selected, and the reported accuracy, the type of AST method and study methodology assessed.</p><p><strong>Results: </strong>In total, 33 studies were identified that met the inclusion criteria (1976-2024). These reported overall CA for direct-from-urine AST ranging from 78.7% to 100% compared to a reference method. These studies varied in the AST method used; in urine sample collection, origin and processing; in the antibiotics evaluated; in study design and data analysis. The most common AST method evaluated was direct-from-urine disc diffusion. Most studies reported accuracy only for samples containing a single Gram-negative organism.</p><p><strong>Conclusion: </strong>Although increasing numbers of studies report the accuracy of direct-from-urine AST, heterogeneity prevented systematic comparison of methods or detailed meta-analysis. Many studies reported overall accuracy >90% CA for urine samples containing a single Gram-negative organism across several direct-from-urine AST methods, offering potential time saving compared with current methods. However, as single organism samples represent only a subset of urines taken from UTI patients, additional studies-that include analysis of samples containing mixed cultures and Gram-positive isolates-are still required.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 4","pages":"dlag170"},"PeriodicalIF":3.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genomic epidemiology and antimicrobial resistance of non-typhoidal Salmonella from retail meats in Beijing, China: implications for foodborne transmission and phage susceptibility.","authors":"Anjie Chen, Huimin Li, Yifei Wang, Xiuhua Hu, Tian Li, Luying Sun, Yang Zuo, Pengcheng Huang, Yu Xi, Yuqi Wang, Yuqing Liu, Ying Zhang, Shaolin Wang","doi":"10.1093/jacamr/dlag182","DOIUrl":"10.1093/jacamr/dlag182","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the prevalence, antimicrobial resistance (AMR) profiles, genomic characteristics and phage susceptibility of non-typhoidal Salmonella (NTS) isolated from retail meats in Beijing, China, and to assess the potential for foodborne transmission and risks associated with phage application.</p><p><strong>Methods: </strong>A total of 583 retail meat samples (pork, chicken, beef, mutton) were collected across Beijing (2021-2022). NTS isolates were identified by serotyping and MALDI-TOF. Antimicrobial susceptibility was tested by broth microdilution. Whole-genome sequencing was performed on 153 isolates for resistome, virulome, plasmid typing and core-genome MLST (cgMLST). Phage lysis assays used 46 phages against representative isolates, and prophages were predicted in silico.</p><p><strong>Results: </strong>NTS prevalence was highest in pork (52.4%) and chicken (43.8%). Dominant serotypes were <i>S.</i> London and <i>S.</i> Enteritidis. Resistance rates were high for sulfisoxazole (74.6%), ampicillin (68.6%) and tetracycline (68.6%); 64.4% of isolates were multidrug-resistant (MDR). Genomic analysis revealed widespread resistance genes (e.g. <i>bla</i> <sub>CTX-M-55</sub>, <i>sul</i>, <i>mph</i>(A)) associated with mobile genetic elements (IS<i>Ecp1</i>, IS<i>91</i>). cgMLST showed high genetic similarity between foodborne isolates and contemporaneous human clinical isolates from multiple provinces. Phage lysis was highly effective against <i>S.</i> Enteritidis (83.3%) but limited against <i>S.</i> Kentucky; 34.0% of isolates carried prophages containing transposons.</p><p><strong>Conclusions: </strong>Retail meats in Beijing, particularly pork and chicken, represent an important reservoir of multidrug-resistant NTS. Comparative genomic analysis revealed close genomic relatedness between retail meat isolates and human clinical isolates, suggesting the potential for foodborne transmission along the food chain. In vitro phage lysis assays demonstrated serotype-dependent susceptibility patterns, highlighting the potential of phage-based control strategies for specific Salmonella serotypes. However, prophages containing transposon-associated sequences were identified in a subset of isolates, and their contribution to horizontal gene transfer warrants further investigation. Enhanced surveillance integrating food, animal, environmental and human clinical Salmonella monitoring, together with serotype-targeted intervention strategies, is needed to support a One Health approach to foodborne disease control.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 4","pages":"dlag182"},"PeriodicalIF":3.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jack K Bradley, Karina Calvopina Tapia, Sabrina J Moyo, Ellinor Shore, Peter Nambala, W David Hong, Christopher J Schofield, Adam P Roberts
{"title":"Covalent inhibition of New Delhi metallo-β-lactamases NDM-1 and NDM-5 by 3-bromopyruvate.","authors":"Jack K Bradley, Karina Calvopina Tapia, Sabrina J Moyo, Ellinor Shore, Peter Nambala, W David Hong, Christopher J Schofield, Adam P Roberts","doi":"10.1093/jacamr/dlag177","DOIUrl":"10.1093/jacamr/dlag177","url":null,"abstract":"<p><strong>Objectives: </strong>Resistance to β-lactam antibiotics, including carbapenems, mediated by metallo-β-lactamases (MBLs), including the New Delhi metallo-β-lactamase (NDM) family, is increasing. No MBL inhibitors are currently approved for clinical use, with most reported MBL inhibitors acting as metal ion chelators at either the Zn(II) ion active site and/or in solution. The hexokinase inhibitor 3-bromopyruvate (3-BP) has been reported to inhibit NDM-1. This study investigates the ability of 3-BP to restore carbapenem activity against NDM-producing bacterial strains.</p><p><strong>Materials and methods: </strong>The ability of 3-BP to restore meropenem activity was assessed against carbapenem-resistant <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i> and <i>Acinetobacter baumannii</i> strains, obtained from clinical and environmental isolates from Tanzania and Malawi. The mechanism of inhibition was investigated using mass spectrometry studies with both biologically relevant sulphur-containing compounds in addition to NDM-1 and NDM-5.</p><p><strong>Results and conclusions: </strong>3-BP selectively restored the antimicrobial activity of meropenem against resistant strains containing genes encoding NDM-1 or NDM-5 but did not restore the antimicrobial activity of amoxicillin against resistant strains containing genes encoding serine β-lactamases. Mass spectrometry studies with NDM-1 and NDM-5 support a mechanism involving covalent reaction of 3-BP with an active site cysteine residue. These results will promote work on the development of covalently reacting MBL inhibitors, a strategy that has been successful for inhibition of the nucleophilic serine β-lactamases.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 4","pages":"dlag177"},"PeriodicalIF":3.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}