Dario Diana, Tommaso Clemente, Diana Canetti, Giovanni Festa, Golnaz Torkjazi, Gaetana Annicchiarico, Anna Danise, Chiara Ballabio, Antonella Castagna, Vincenzo Spagnuolo
{"title":"First virological control after >30 years of antiretroviral therapy in extensively drug-resistant HIV: potential role of lenacapavir plus ibalizumab.","authors":"Dario Diana, Tommaso Clemente, Diana Canetti, Giovanni Festa, Golnaz Torkjazi, Gaetana Annicchiarico, Anna Danise, Chiara Ballabio, Antonella Castagna, Vincenzo Spagnuolo","doi":"10.1093/jac/dkag316","DOIUrl":"https://doi.org/10.1093/jac/dkag316","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 10","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944607","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}
Philippe Poirier, Maxime Moniot, Virginie Bonnin, Gaëlle Castan, Patricia Combes, Céline Nourrisson
{"title":"Systematic screening identified broad-spectrum inhibitors of human-pathogenic Encephalitozoon species and revealed no in vitro activity of nitazoxanide.","authors":"Philippe Poirier, Maxime Moniot, Virginie Bonnin, Gaëlle Castan, Patricia Combes, Céline Nourrisson","doi":"10.1093/jac/dkag319","DOIUrl":"10.1093/jac/dkag319","url":null,"abstract":"<p><strong>Background: </strong>Microsporidia are obligate intracellular eukaryotic pathogens infecting a wide range of vertebrate and invertebrate hosts. Therapeutic options for microsporidiosis remain limited in both human and veterinary medicine.</p><p><strong>Objectives: </strong>The goal was to screen the 400 compounds of the open-access Pandemic Response Box, provided by the Medicines for Malaria Venture foundation, for their anti-microsporidia activity.</p><p><strong>Methods: </strong>The compounds were screened at 1 µM against Encephalitozoon cuniculi, E. intestinalis and E. hellem using an ELISA-based assay. Selected compounds were further evaluated by determining their in vitro cytotoxicity and their IC50 values.</p><p><strong>Results: </strong>Preliminary screening revealed promising efficacy of eight compounds against the three species. Trimetrexate was the most active compound, with IC50 values < 1 µM and selectivity index > 100 for all three species. Triapine exhibited intermediate activity, with IC50 values ranging from 1 to 2 µM. Nitazoxanide failed to achieve 50% growth inhibition at the highest concentration tested (2 µM) against any of the three species.</p><p><strong>Conclusions: </strong>Trimetrexate emerged as the most promising candidate for further anti-microsporidia exploration, whereas nitazoxanide showed no detectable activity under the conditions tested, questioning its role in the treatment of human microsporidiosis.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 10","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919716","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":"Cefoxitin versus cefotaxime as empirical treatment of spontaneous bacterial peritonitis in liver cirrhotic patients: randomized controlled clinical trial.","authors":"M A M Ebrahim, M A M Nasr, M M M Abdel-Latif","doi":"10.1093/jac/dkag318","DOIUrl":"10.1093/jac/dkag318","url":null,"abstract":"<p><strong>Background: </strong>Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhosis requiring immediate empirical antibiotic therapy. Third-generation cephalosporins are the traditional agents of choice; however, increasing clinical failure rates necessitate the evaluation of alternative antibiotics to ensure optimal therapeutic outcomes. The aim was to investigate the efficacy of cefoxitin versus cefotaxime for SBP treatment.</p><p><strong>Methods: </strong>A randomized clinical trial was conducted on 140 cirrhotic patients with community-acquired SBP at Al-Rajhy Liver University Hospital, Assiut, Egypt. Patients were randomized to receive either cefotaxime (n = 70) or cefoxitin (n = 70), 2 g every 8 h for 5 days. Polymorphonuclear neutrophil (PMN) counts were measured upon admission, on Day 2 and on Day 5. Clinical response rates at Days 2 and 5, development of hepatorenal syndrome, length of stay and mortality were assessed.</p><p><strong>Results: </strong>According to intention-to-treat analysis, clinical response rates at Day 2 were 74.2% in the cefotaxime group and 80% in the cefoxitin group, while at Day 5, they were 71.4% and 74.3%, respectively (P = 0.704). The PMN counts at Days 0, 2 and 5 showed no significant differences between the cefotaxime and cefoxitin groups (P = 0.889, 0.909 and 0.360, respectively). The incidence of hepatorenal syndrome was 7.1% in the cefotaxime group compared with 8.6% in the cefoxitin group (P = 0.753), and mortality was 15.7% and 12.9%, respectively (P = 0.629).</p><p><strong>Conclusions: </strong>Cefoxitin showed comparable effectiveness to cefotaxime but may be utilized in selected clinically stable SBP patients.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 10","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968853","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":"Performance of a rapid direct-from-blood antibiotic susceptibility test based on MIC test strips on Enterobacterales blood cultures.","authors":"Tassadit Nait Larbi, Hélène Poupet, Céline Plainvert, Philippe Morand, Sarrah Boukthir, Julien Loubinoux, Alexandra Doloy, Lamia Rouabah, Claire Poyart, Asmaa Tazi, Hedi Mammeri","doi":"10.1093/jac/dkag312","DOIUrl":"https://doi.org/10.1093/jac/dkag312","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the technical performance of a rapid direct-from-blood antibiotic susceptibility test (AST) using MIC test strips (MTS-AST) directly on enterobacteria-positive blood culture broth.</p><p><strong>Methods: </strong>Fifty contrived blood culture bottles (BACT/ALERT FA plus) were prepared using 10 mL of sheep blood and a diluted bacterial suspension. A collection of 50 enterobacterial isolates was used, including 25 strains previously recovered from blood cultures and 25 additional strains exhibiting various mechanisms of resistance. Blood culture bottles were incubated in the BACT/ALERT VIRTUO system until they flagged positive. Then they were pulled and two drops of blood culture broth (approximately 100 µL) were directly poured and streaked onto a Mueller-Hinton agar plate. MIC test strips were immediately laid on the plate, before incubation at 35°C ± 1°C in an aerobic atmosphere for 5 h. Seven β-lactams were tested including amoxicillin, amoxicillin/clavulanate, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime and meropenem. Comparator MICs were obtained using MIC test strips according to the manufacturer's instructions with a standardized inoculum and 24 h of incubation. Essential agreement (EA), categorical agreement (CA) and bias were determined.</p><p><strong>Results: </strong>EA and CA between the MTS-AST and the comparator method were ≥94% and ≥90%, respectively, with no very major error. Positive bias was apparent for all antibiotics.</p><p><strong>Conclusions: </strong>MTS-AST provided rapid results (in 5 h) that correlated well with the comparator method on blood culture broth containing Enterobacterales. Given the shorter time to results, the reduced time cost, the limited handwork and the reduced cost per test, the MTS-AST constitutes a fast and reliable method.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 10","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017000","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}
Mehdi El Hassani, Daniel J G Thirion, Aysenur Yaliniz, Katherine Desforges, Josée Verdon, Emily G McDonald, Amélie Marsot
{"title":"Do current oral ciprofloxacin regimens achieve pharmacokinetic/pharmacodynamic targets within safe exposure limits in older adults with Pseudomonas aeruginosa infection? A population pharmacokinetic analysis.","authors":"Mehdi El Hassani, Daniel J G Thirion, Aysenur Yaliniz, Katherine Desforges, Josée Verdon, Emily G McDonald, Amélie Marsot","doi":"10.1093/jac/dkag283","DOIUrl":"https://doi.org/10.1093/jac/dkag283","url":null,"abstract":"<p><strong>Background: </strong>Ciprofloxacin is one of the few orally available antibiotics with activity against Pseudomonas aeruginosa. This study developed a population pharmacokinetic (popPK) model for oral ciprofloxacin in older adults and evaluated whether standard regimens achieve the pharmacokinetic/pharmacodynamic (PK/PD) target of 24 h area under the concentration-time curve over minimal inhibitory concentration (AUC0-24/MIC) ≥ 125.</p><p><strong>Methods: </strong>This was a prospective pilot study in patients ≥75 years taking oral ciprofloxacin at the McGill University Health Centre, Canada. Plasma samples were collected at steady state (peak, mid-interval, trough) and data fitting was performed using NONMEM with stochastic approximation expectation-maximization. Monte Carlo simulations (n = 1000) assessed the probability of target attainment (PTA) for standard dosing regimens of 250-750 mg q12h across MICs of 0.125-2 mg/L.</p><p><strong>Results: </strong>Fifteen patients (median age 82 years, weight 75 kg, creatinine clearance 46 mL/min) contributed 42 plasma concentrations to the analysis. A one-compartment model with first-order absorption and elimination best described the data. Population mean apparent clearance and volume of distribution were 14.3 L/h and 247 L, respectively (resulting in a 12 h half-life), with high interindividual variability (IIV: 75.2% and 36.0%). The absorption rate constant was fixed to 2.5 h-1. No covariate effects were retained in the final model. At the P. aeruginosa clinical MIC breakpoint of 0.5 mg/L, standard regimens achieved PTAs of 18.7% (250 mg q12h), 56.6% (500 mg q12h), and 76.5% (750 mg q12h).</p><p><strong>Conclusions: </strong>This first popPK model for oral ciprofloxacin specifically in older adults demonstrates that simulated standard dosing regimens fail to achieve PK/PD targets for P. aeruginosa. The large IIV, increased drug exposure and low target attainment support implementation of therapeutic drug monitoring in this population.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759552","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":"Genome-wide network of antibiotic susceptibility in Pseudomonas aeruginosa.","authors":"Océane Goncalves, Jean-Philippe Côté","doi":"10.1093/jac/dkag272","DOIUrl":"10.1093/jac/dkag272","url":null,"abstract":"<p><strong>Background and objective: </strong>Pseudomonas aeruginosa is a ubiquitous Gram-negative pathogen notorious for causing infections with high mortality rates. Its large genome supports extensive metabolic diversity and promotes its adaptation to diverse environments. The survival and persistence of P. aeruginosa in clinical settings is further facilitated by a vast arsenal of strategies that contribute to its tolerance or resistance to antibiotics. Here, we aimed to systematically identify the genetic determinants that affect its susceptibility to antibiotics.</p><p><strong>Methods: </strong>The ordered PA14 transposon mutant library was grown in the presence of sub-MIC concentrations of a panel of antibiotics of various classes, and the growth of each mutant was quantified to generate susceptibility scores.</p><p><strong>Results: </strong>We observed a dense network of genes affecting antibiotic susceptibility in P. aeruginosa, where a large portion of genes modulated susceptibility to various classes of antibiotics. Not surprisingly, efflux and outer membrane permeability were key contributors, but we also identified genes that are not typically associated with antibiotic susceptibility.</p><p><strong>Conclusions: </strong>The data provide a genome-wide view of the antibiotic susceptibility network in P. aeruginosa. Overall, our approach deepens our understanding of antibiotic susceptibility and opens new avenues for developing strategies against multidrug-resistant P. aeruginosa.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juan Martin-Torres, Roser Navarro-Soler, Judit Iglesias-Franco, María Lagarde-Sebastián, Otilia Bisbal-Pardo, David Rial-Crestelo, Adriana Pinto-Martínez, Maria Belén Sánchez-López, Mireia Santacreu, Laura Bermejo, Asunción Hernando, Rafael Rubio, Federico Pulido
{"title":"Effectiveness of dolutegravir/lamivudine versus bictegravir/emtricitabine/tenofovir alafenamide in people with HIV with very high viral load (≥500 000 copies/mL).","authors":"Juan Martin-Torres, Roser Navarro-Soler, Judit Iglesias-Franco, María Lagarde-Sebastián, Otilia Bisbal-Pardo, David Rial-Crestelo, Adriana Pinto-Martínez, Maria Belén Sánchez-López, Mireia Santacreu, Laura Bermejo, Asunción Hernando, Rafael Rubio, Federico Pulido","doi":"10.1093/jac/dkag285","DOIUrl":"10.1093/jac/dkag285","url":null,"abstract":"<p><strong>Objectives: </strong>To compare the effectiveness of dolutegravir/lamivudine (DTG/3TC) versus bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) at Week 48 in treatment-naive adults with high baseline viral loads (≥500 000 copies/mL) and CD4+ cell count ≥200/mm3 and to assess immune recovery and safety.</p><p><strong>Methods: </strong>We conducted a single-centre retrospective cohort study including all ART-naive people with HIV-1 (PWH) and HIV-RNA ≥500 000 copies/mL and CD4+ ≥200 cells/mm3 who initiated DTG/3TC or BIC/FTC/TAF during 2019-2024. Effectiveness was assessed as the proportion of participants achieving HIV-1 RNA <50 copies/mL at Week 48 [intention-to-treat, missing = failure (ITT, M = F)]. Immune recovery, metabolic and renal safety were evaluated through changes in CD4+ count, weight, lipid profile and creatinine. Time-to-virologic suppression was analysed using Kaplan-Meier curves and log-rank testing. Safety profile and immune recovery were conducted using Mann-Whitney U test.</p><p><strong>Results: </strong>A total of 40 patients (52.5% on DTG/3TC, 47.5% on BIC/FTC/TAF) were included, with a high prevalence of primary HIV infection (PHI) (76.2% and 84.2%, respectively). No baseline differences were observed between groups. At 48 weeks, virologic suppression rates were 90.5% (19/21) in the DTG/3TC group and 94.7% (18/19) in the BIC/FTC/TAF group (log-rank P = 0.73). Viral decay kinetics were similar between groups. No virologic failures with resistance or treatment discontinuations were observed. Median CD4+ gains were comparable between groups (385 vs 243 cells/mm3; P = 0.30). No significant differences in weight gain, lipid profile, or creatinine levels were observed.</p><p><strong>Conclusions: </strong>In ART-naive PWH with HIV-RNA ≥500 000 cp/mL and CD4+ ≥200/mm3, including those with PHI, DTG/3TC and BIC/FTC/TAF showed similar effectiveness and comparable safety profiles at Week 48.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793384","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":"Is there any role for empiric coverage of resistant Gram-positive bacteria in febrile neutropaenia?","authors":"Marcio Nucci, Simone A Nouér","doi":"10.1093/jac/dkag294","DOIUrl":"10.1093/jac/dkag294","url":null,"abstract":"<p><p>Vancomycin is still frequently started empirically in febrile neutropaenia, especially when patients are severely ill. Yet randomized evidence concerning anti-Gram-positive agents as a class shows no mortality benefit from routine empirical coverage, and contemporary cohort studies consistently link early shock and death to Gram-negative bacilli, inadequate Gram-negative coverage, pneumonia, septic shock and candidaemia rather than to Gram-positive bacteraemia or inadequate Gram-positive coverage. MRSA nasal screening further supports avoiding empirical anti-MRSA therapy in screen-negative patients. The default response to febrile neutropaenia should therefore be rapid, locally informed anti-pseudomonal beta-lactam therapy, with vancomycin reserved for documented infection or narrowly defined syndromes with a high pre-test probability of resistant Gram-positive disease.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812813","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}
Tianle Pan, Lian Liu, Ruyue Huang, Mi Wang, Chenzhong Fei, Yingchun Liu
{"title":"Study on the synergistic activity of G-749 and colistin against Escherichia coli.","authors":"Tianle Pan, Lian Liu, Ruyue Huang, Mi Wang, Chenzhong Fei, Yingchun Liu","doi":"10.1093/jac/dkag301","DOIUrl":"10.1093/jac/dkag301","url":null,"abstract":"<p><strong>Objectives: </strong>In order to investigate the synergistic antibacterial effects of the novel FLT3 inhibitor G-749 in combination with colistin against Escherichia coli (E. coli).</p><p><strong>Methods: </strong>The in vitro antibacterial activity of G-749 combined with colistin was evaluated by MIC using the broth microdilution method, followed by checkerboard synergy testing and time-kill assays. The in vivo efficacy was assessed in a murine thigh infection model using mcr-positive colistin-resistant strain M17GZZ15. Mechanistic studies employed propidium iodide (PI) and 4',6-diamidino-2-phenylindole (DAPI) staining to evaluate bacterial membrane integrity and nucleic acid content. The pharmacokinetic profile of G-749 was characterized in mice after a single oral dose of 100 mg/kg body weight.</p><p><strong>Results: </strong>G-749 significantly potentiated colistin activity, reducing the MIC of colistin by 16- to 64-fold against susceptible E. coli ATCC25922 and by 8- to 32-fold against the resistant strain M17GZZ15. Time-kill assays revealed rapid bactericidal effects within 4 h. In the murine thigh infection model, the combination therapy significantly reduced bacterial burdens compared with monotherapy (P < 0.01). Mechanistic investigations showed enhanced PI uptake, indicating increased membrane permeability, and diminished DAPI fluorescence, suggesting intracellular nucleic acid leakage. Pharmacokinetic profiling of G-749 yielded a Cmax of 17.94 mg/L at Tmax 0.67 h, an AUC0-24 of 44.91 mg·h/L, and an elimination half-life of 3.34 h.</p><p><strong>Conclusions: </strong>These findings establish G-749 as a potent colistin adjuvant that acts primarily by augmenting membrane disruption, with oxidative stress and energy suppression potentially contributing at higher concentrations, thereby improving antibacterial efficacy against Gram-negative bacteria. This multi-mechanistic and concentration-dependent synergistic profile offers a promising strategy to combat multidrug-resistant infections.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840279","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}
Rikki Franklin Frederiksen, Silje Granstad, Ida Thøfner, Jannice Schau Slettemeås, Karin Lagesen, Anne Margrete Urdahl, Roger Simm
{"title":"Narasin used as a feed additive in conventional rearing of broilers can co-select for vancomycin-resistant Enterococcus faecium through the NarAB ionophore resistance mechanisms.","authors":"Rikki Franklin Frederiksen, Silje Granstad, Ida Thøfner, Jannice Schau Slettemeås, Karin Lagesen, Anne Margrete Urdahl, Roger Simm","doi":"10.1093/jac/dkag253","DOIUrl":"10.1093/jac/dkag253","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the role of the NarAB resistance mechanism in the selection of vancomycin-resistant Enterococcus faecium (VREfm) and assess the impact of ionophore feed additives, particularly narasin, on the emergence of VREfm in broiler chickens.</p><p><strong>Materials and methods: </strong>Three isogenic E. faecium strains with different antimicrobial resistance determinants were created by mutagenesis and conjugation and used in a controlled animal experiment. Ross 308 broiler chickens were inoculated with either a rifampicin-resistant, a rifampicin- and vancomycin-resistant or a rifampicin-, vancomycin- and narasin-resistant strain and fed diets supplemented with selected ionophores. Bacterial populations were analysed on selective Slanetz and Bartley agar to determine the presence and selection of VREfm and other vancomycin-resistant species. Bacterial inoculation strains and isolates were whole genome sequenced for species identification and to identify genetic resistance mechanisms.</p><p><strong>Results: </strong>Narasin was shown to select for VREfm in broilers, with NarAB being essential for co-selection. Intrinsically vancomycin-resistant Pediococcus acidilactici and Enterococcus gallinarum were identified as part of the broilers' vancomycin-resistant resident microbiota. Notably, among the P. acidilactici isolates that were susceptibility tested, strains resistant to both vancomycin and narasin were only found in broilers fed narasin, supporting that narasin promotes the growth of narasin-resistant populations.</p><p><strong>Conclusion: </strong>Narasin use in broiler feed can co-select for vancomycin-resistant bacteria, including VREfm, through the NarAB mechanism. These findings emphasize the concerns associated with the use of particular ionophores in poultry and suggest that vancomycin and narasin resistance may be more widespread in the broiler microbiota than previously recognized. Further research is needed to understand the implications for antimicrobial resistance and human health.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}