Journal of Antimicrobial Chemotherapy最新文献

{"title":"Tetracyclines at subinhibitory concentrations are lethal for NADH peroxidase-deficient mutants of Enterococcus faecium.","authors":"Valentin Wasselin, Aurélie Budin-Verneuil, Isabelle Rincé, Florie Desriac, Julie Plouhinec, Amine M Boukerb, Axel Hartke, Abdellah Benachour, Eliette Riboulet-Bisson","doi":"10.1093/jac/dkaf105","DOIUrl":"10.1093/jac/dkaf105","url":null,"abstract":"<p><strong>Objectives: </strong>Tigecycline is a bacteriostatic antibiotic member of the glycylcycline family that inhibits protein synthesis. Tigecycline is a last-line treatment for infections caused by MDR pathogens like vancomycin-resistant Enterococcus faecium (VR-Efm). We recently explored oxidative stress defences in E. faecium and we here aimed to assess their role in antibiotic resistance.</p><p><strong>Methods: </strong>Antibiotic susceptibility was evaluated in mutants deficient in primary oxidative stress defences by monitoring bacterial survival after a 24 h treatment. Hydrogen peroxide (H2O2) levels were quantified to link bacterial survival to oxidative stress.</p><p><strong>Results: </strong>Unexpectedly, tigecycline and other tetracyclines were lethal for VR-Efm AUS0004 mutants deficient in NADH peroxidase (Npr) at concentrations below their MICs. Lethality seemed to correlate with increased H2O2 accumulation in the Δnpr mutant. H2O2 production in Efm AUS0004 was mainly mediated by lactate oxidase Lox1, whereas Lox2 and pyruvate oxidase (Pox) had minor or no roles. Tigecycline was not lethal for a ΔnprΔlox1 double mutant, suggesting lethality results from both antibiotic effect and peroxide accumulation.</p><p><strong>Conclusions: </strong>This study might pave the way to develop strategies aimed at potentiating tigecycline action by increasing endogenous H2O2 production and/or impairing H2O2 detoxification, potentially improving treatment efficiencies for VR-Efm infections with this last-line antibiotic.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1587-1594"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019652","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":"Correction to: Linezolid brain penetration in neurointensive care patients.","authors":"","doi":"10.1093/jac/dkaf099","DOIUrl":"10.1093/jac/dkaf099","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1751"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657025","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}

{"title":"Interventions to improve antibiotic use among dentists: a systematic review and meta-analysis.","authors":"Julieta Mendez-Romero, Almudena Rodríguez-Fernández, Marta Ferreira, Ulises Villasanti, Gloria Aguilar, Carlos Rios-Gonzalez, Adolfo Figueiras","doi":"10.1093/jac/dkaf118","DOIUrl":"10.1093/jac/dkaf118","url":null,"abstract":"<p><strong>Objectives: </strong>To analyse the effectiveness of various strategies, such as audits, education and digital tools, in reducing inappropriate antibiotic prescription by dentists. This study provides a comprehensive overview of how such interventions can contribute to improving clinical practice and combatting antimicrobial resistance in the dental setting.</p><p><strong>Methods: </strong>An electronic search of articles published until 2023 in the following databases was performed: MEDLINE, SCOPUS, EMBASE, COCHRANE CENTRAL, LILACS and BBO. Systematic data synthesis and meta-analysis was carried out. A total of 23 studies regarding interventions to reduce antibiotic prescription among dentists were included. The studies were mostly published in the UK between 1997 and 2023. Of the 23 studies, three were trials and 20 were pre-post studies.</p><p><strong>Results: </strong>In general, interventions among dentists resulted in a 70% reduction in the inappropriate prescription of antibiotics (95% CI: 33.3% to 86.4%), which is an extremely high percentage. In the pre-post studies, the reduction was 71% (95% CI 28.8%-88.1%) I2 99.2%. In randomized controlled trial studies, a 63.9% (95% CI 41%-78.1%) I2 0% reduction was achieved. The greatest magnitude of effect was found in audit-based interventions with audit and education intervention at 73.3% (95% CI 44%-87.4%) and audit and feedback 75% (95% CI 33%-91.4%), respectively. However, the quality of the evidence is low, mostly due to the study design.</p><p><strong>Conclusion: </strong>Given the magnitude of the effect found, it has been shown that dentists are receptive to improving their prescription of antibiotics. However, it is clear that there is ample room for improvement.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1494-1507"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991312","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}

{"title":"Long-term durability of dolutegravir plus darunavir/cobicistat dual regimen in highly antiretroviral-experienced people with HIV (DoDaco study).","authors":"Diego Ripamonti, Laura Comi, Andrea Francavilla, Daniela Valenti, Maria Vittoria Cossu, Davide Moschese, Giuseppe Lapadula, Luca Mezzadri, Paolo Bonfanti, Maria Mazzitelli, Annamaria Cattelan, Roberto Gulminetti, Layla Pagnucco, Massimiliano Fabbiani, Teresa Bini, Maurizio Zazzi, Andrea Giacomelli","doi":"10.1093/jac/dkaf119","DOIUrl":"10.1093/jac/dkaf119","url":null,"abstract":"<p><strong>Background: </strong>A dolutegravir plus darunavir/cobicistat regimen has been used as a simplified option in heavily treatment-experienced people with HIV (PWH). We report on long-term results of this regimen as assessed by treatment discontinuation (TD) for any reason.</p><p><strong>Methods: </strong>This was a retrospective, observational, multicentre study. PWH started on dolutegravir plus darunavir/cobicistat from 1 December 2015 to 31 December 2022 were included. The primary endpoint was the rate of TD for any reason. Survival analysis with the Kaplan-Meier estimator was used to assess the probability of TD over time. Multiple Cox regression was used to estimate the probability of TD at 1 year following regimen initiation.</p><p><strong>Results: </strong>Three hundred and twenty-seven subjects were included. At baseline, 63.6% of individuals had HIV RNA of <50 copies/mL. Primary resistance-associated mutations for NRTIs, NNRTIs, PIs and integrase inhibitors were documented in 88.0%, 70.0%, 24.5% and 6.6%, respectively. Median follow-up was 4 years (IQR 3.3-6.9). Probability of TD was 8.3%, 13.0%, 18.0%, 22.0%, 25.0%, 30.0% and 35.0% after 1, 2, 3, 4, 5, 6 and 7 years of treatment, respectively. TD occurred in 83 subjects, largely due to death (n = 20), simplification (n = 13), toxicity (n = 11), intolerance (n = 9), drug interactions (n = 10) and virological failure (n = 7). At Cox regression analysis, factors associated with a higher probability of TD over time were baseline HIV RNA of >50 copies/mL (HR = 2.14, 95% CI 1.20-3.81; P = 0.01) and the presence of PI or integrase strand transfer inhibitor resistance mutations (HR = 5.48, 95% CI 2.42-12.4; P < 0.001).</p><p><strong>Conclusions: </strong>Dolutegravir plus darunavir/cobicistat is a durable combination in heavily treatment-experienced PWH. Those who were viraemic at the time of switch were more likely to discontinue, although most reasons for TD were other than virological failure.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1665-1672"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984884","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":"Ibrexafungerp prolongs survival and reduces the eumycetoma grain size in Galleria mellonella infection models of two different causative agents of eumycetoma.","authors":"Jingyi Ma, Kimberly Eadie, Mickey Konings, Ahmed Fahal, Annelies Verbon, Wendy W J van de Sande","doi":"10.1093/jac/dkaf133","DOIUrl":"10.1093/jac/dkaf133","url":null,"abstract":"<p><strong>Objectives: </strong>Eumycetoma is a neglected tropical fungal disease of the subcutaneous tissue that is currently not treatable with medication only. Standard itraconazole therapy is combined with surgical excision of the lesion. Recently, ibrexafungerp, a novel oral antifungal agent inhibiting 1,3-β-D-glucan synthesis, was approved by the United States Food and Drug Administration (FDA) for the treatment of vulvovaginal candidiasis. In this study we determined the in vitro activity and in vivo efficacy of ibrexafungerp in eumycetoma causative agents.</p><p><strong>Methods: </strong>In vitro activity of ibrexafungerp and itraconazole was determined against 30 Madurella and 7 Falciformispora isolates by standardized in vitro susceptibility assays. The in vivo efficacy of ibrexafungerp, itraconazole and the combination of ibrexafungerp and itraconazole was determined by measuring the 10 day survival in M. mycetomatis and F. senegalensis grain models in Galleria mellonella larvae. Grain number and size were determined in Grocott- and haematoxylin and eosin-stained sections.</p><p><strong>Results: </strong>Ibrexafungerp inhibited the growth of Madurella and Falciformispora species with MICs ranging from 4 to 64 mg/L and from 8 to 32 mg/L, respectively. In G. mellonella larvae, ibrexafungerp was not toxic and prolonged the survival in M. mycetomatis-infected larvae 10 days after infection, but not in F. senegalensis-infected larvae. Combining ibrexafungerp with itraconazole prolonged the survival of M. mycetomatis- and F. senegalensis-infected larvae. Treatment with ibrexafungerp alone and in combination resulted in smaller grains in M. mycetomatis-infected larvae.</p><p><strong>Conclusions: </strong>Ibrexafungerp showed in vitro activity and in vivo efficacy against the two most common eumycetoma causative agents.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1733-1741"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982030","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}

{"title":"Appropriateness of loading dose and TDM in patients treated with teicoplanin: a single-centre observational retrospective cohort study comparing single-daily and thrice-weekly regimens.","authors":"Alessandra Helen Behring, Chiara Mariani, Martina Gerbi, Martina Offer, Maddalena Matone, Dario Cattaneo, Andrea Giacomelli, Marta Colaneri, Riccardo Giorgi, Stefania Merli, Stefania Piconi, Spinello Antinori, Andrea Gori, Matteo Passerini","doi":"10.1093/jac/dkaf097","DOIUrl":"10.1093/jac/dkaf097","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the appropriateness of teicoplanin loading dose and therapeutic drug monitoring (TDM) in single-daily regimen (SDR) versus thrice-weekly regimen (TWR), and to compare safety and effectiveness.</p><p><strong>Methods: </strong>This single-centre observational retrospective cohort study included adult patients treated with TDM-based teicoplanin for infections between April 2015 and December 2021. Appropriateness of loading dose and TDM, adverse events (AEs) and clinical outcomes were evaluated. A post hoc analysis assessed achievement of target TDM concentrations following appropriate loading dose.</p><p><strong>Results: </strong>Among 183 patients (103 SDR, 80 TWR), appropriate loading doses were less frequent in the SDR group [33/103 (35.9%, missing = 11) versus 56/80 (72.7%, missing = 3); P < 0.001]. First TDM was less commonly performed as recommended in the SDR group on Day 4 [89/103 (86.4%) versus 79/80 (98.8%); P = 0.002] and on Day 7 [31/103 (30.1%) versus 47/80 (58.8%); P < 0.001]. No significant differences were observed in AEs [15/103 (14.6%) versus 8/80 (10%); P = 0.38] or clinical success [60/103 (58.3%) versus 49/80 (61.3%); P = 0.681] between groups. Post hoc analysis showed that 2/16 (13%) patients with deep infections and 9/11 (82%) with non-deep infections on a TWR achieved target concentrations after loading dose.</p><p><strong>Conclusions: </strong>Higher adherence to loading dose and TDM recommendations was observed for TWR compared with SDR. However, the TWR often failed to achieve adequate TDM levels for higher targets, highlighting the need for optimized TWR loading dose strategies.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1535-1542"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742836","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":"Dual versus sequenial therapy using rifaximin and MTZ in a patient with intestinal methanogen overgrowth-a case report.","authors":"Gernot Kriegshäuser","doi":"10.1093/jac/dkaf107","DOIUrl":"10.1093/jac/dkaf107","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1744-1746"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752756","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 resistance and population structure of Staphylococcus epidermidis from prosthetic joint infections in Sweden and France.","authors":"Sofie M Edslev, Frederic Laurent, Emeli Månsson, Thor Bech Johannesen, Mia Aarris, Ute Wolff Sönksen, Camille Kolenda, Bo Söderquist, Marc Stegger","doi":"10.1093/jac/dkaf166","DOIUrl":"https://doi.org/10.1093/jac/dkaf166","url":null,"abstract":"<p><strong>Background and objectives: </strong>Staphylococcus epidermidis is a major cause of prosthetic joint infections (PJIs). Multidrug resistant (MDR), hospital-adapted clones constitute most cases globally, though regional differences in lineage dissemination likely exist. The aim was to explore the population structure of S. epidermidis from PJIs in Sweden and France, with a focus on the presence of antimicrobial resistance (AMR).</p><p><strong>Methods: </strong>This study included genome sequence data from 191 clinical S. epidermidis isolates collected from patients with PJI in central Sweden (2007-16; n = 138) and the Lyon region in France (2015-20; n = 53).</p><p><strong>Results: </strong>Hospital-adapted lineages with a high burden of AMR dominated the cases in both countries. However, the ST2 lineage was significantly more prevalent in Sweden (43% versus 11% in France), while ST5 and ST87 were more common in France (55% versus 10% in Sweden). ST215 was only present in Sweden (25%). A significantly higher prevalence of streptogramin resistance genes [vat(B), vga(A), vga(B)] was found in French (26%) versus Swedish (2%) isolates. These genes were present in all ST87 isolates and in 20% of the French ST5 isolates. The erm(C) gene (resistance to streptogramin A, macrolides and lincosamides) was also more common in the French isolates (77% versus 55% of Swedish isolates), and so was the fusidic acid resistance gene fusB (France: 66%, Sweden: 39%).</p><p><strong>Conclusions: </strong>This study highlights significant regional differences in S. epidermidis variants causing PJI. Despite similar MDR levels, certain AMR genes, particularly those related to streptogramin resistance, were significantly more prevalent among French isolates. This suggests that S. epidermidis undergoes local adaptation to region-specific antibiotic usage.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208532","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":"Activity of rezafungin against Candida auris.","authors":"Jeffrey B Locke, David Andes, Shawn Flanagan, Mark Redell, Voon Ong, Jalal A Aram, Peter G Pappas, Mariana Castanheira, George R Thompson","doi":"10.1093/jac/dkaf124","DOIUrl":"10.1093/jac/dkaf124","url":null,"abstract":"<p><p>The increasing prevalence of candidemia and invasive candidiasis infections caused by Candida auris represents a global health risk. Such infections are difficult to treat as they are often multidrug-resistant and are linked to high rates of mortality. Rezafungin is a second-generation echinocandin with antifungal activity against a range of Candida species, including wild type, and azole- and some echinocandin-resistant isolates. Its stability and prolonged half-life permit less frequent dosing compared with other echinocandins, leading to high front-loaded exposures and potential earlier mycological clearance from infection sites. These properties make rezafungin a candidate for the treatment of candidemia and invasive candidiasis infections due to C. auris. Accordingly, this narrative review article describes available evidence for the activity and effectiveness of rezafungin against C. auris isolates and infections. To date, the activity of rezafungin against C. auris isolates and infections has been demonstrated in in vitro and in vivo non-clinical experiments, and in pharmacokinetic/pharmacodynamic target attainment estimations utilizing clinical data. With similar potency to other echinocandins, rezafungin demonstrates in vitro and in vivo activity that is comparable to or better than that seen with other echinocandins, and similar to that for rezafungin in other Candida species. Like other echinocandins, its activity is reduced in fks-mutant isolates. Although there is currently a dearth of data on the therapeutic activity of rezafungin against C. auris, it is reasonable that rezafungin may be a viable choice for treating candidemia and invasive candidiasis caused by C. auris. Further clinical investigations are necessary.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1482-1493"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025413","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}

{"title":"Unravelling the genetic contributors to linezolid resistance in Mycobacterium smegmatis: insights from a transposon library.","authors":"Dachuan Lin, Yuanyi Zhang, Zhifei Luo, Jing Wang, Xinchun Chen","doi":"10.1093/jac/dkaf106","DOIUrl":"10.1093/jac/dkaf106","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to identify and characterize genes associated with linezolid resistance in Mycobacterium smegmatis using a transposon mutagenesis approach.</p><p><strong>Methods: </strong>This research conducted three replicative experiments where 16 isolates displaying pronounced resistance to linezolid were examined, revealing two distinct morphologies. WGS was employed to investigate these isolates, uncovering mutations in specific genes. The binding affinity of linezolid to relevant proteins was assessed through molecular docking studies and validated by drug affinity responsive target stability (DARTS) assays.</p><p><strong>Results: </strong>Complementation of the mspA gene in mutant strains restored linezolid susceptibility, but the Ala127Gln substitution in MSMEG_0965 did not, suggesting a critical role of this residue in resistance. Further investigations revealed that the resistance mechanism in the △MSMEG_0965 mutant involves impaired linezolid uptake.</p><p><strong>Conclusions: </strong>The research successfully identified two genes, MSMEG_4189 and MSMEG_0965, associated with linezolid resistance in M. smegmatis. It also elucidated the role of MSMEG_0965 in the resistance mechanism, providing significant targets and reference points for future studies on clinical strains.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1595-1603"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772386","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}