International Journal of Antimicrobial Agents最新文献

{"title":"Combining minocycline with polymyxin B against Klebsiella pneumoniae in neutropenic murine infection models: one plus one is more than two.","authors":"Anouk E Muller, Chenyan Zhao, Brenda C M de Winter, Marian T Ten Kate, Aart van der Meijden, Vincent Aranzana-Climent, Helene Mirfendereski, Lena E Friberg, Sanne van den Berg, Joseph Meletiadis","doi":"10.1016/j.ijantimicag.2026.108036","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2026.108036","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic options for multidrug-resistant Klebsiella pneumoniae are limited and combination therapy is often used. In vitro studies suggested that minocycline and polymyxin B may act synergistically. We studied this antibiotic combination in neutropenic murine K. pneumoniae infection models.</p><p><strong>Materials: </strong>The PK/PD-index for minocycline against K. pneumoniae was determined in neutropenic murine thigh (N=2 strains) and lung (N=1 strain) infection models, followed by minocycline target assessment (N=4 thigh; N=2 lung). Subsequently, suboptimal polymyxin B dose levels were added to minocycline in both thigh (N=2) and lung (N=1) models. An interaction index was calculated based on Loewe additivity theory.</p><p><strong>Results: </strong>Overall, the antibacterial effect of minocycline correlated best with fAUC/MIC and was subsequently used as PK/PD-index. No killing was observed, whereas stasis was found only in the thigh infection model for 2 of 4 strains with minocycline fAUC/MIC of 18.9 and 24.5, respectively. In the combination experiments, stasis and 1-log₁₀ kill were reached in experiments at subtherapeutic polymyxin B levels (6.5-36.6 fAUC/MICs) with minocycline fAUC/MICs of 3.1-14.5 for stasis and 8.4-26.1 for 1-log₁₀ kill. This synergistic effect was confirmed by the interaction indices of 0.16-0.66 in the thigh- and 0.44-0.77 in the lung-infection model.</p><p><strong>Conclusion: </strong>Minocycline monotherapy is not adequate to treat K. pneumoniae infections. Minocycline plus polymyxin B is synergistic reaching a 1-log₁₀ kill effect in all 3 combination experiments and a 2-log₁₀ kill effect in one strain. Based on limited human PK, high human minocycline doses may be needed to reach the required exposure for stasis.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"108036"},"PeriodicalIF":5.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206928","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":"Corrigendum to \"Eliminating the tigecycline resistance RND efflux pump gene cluster tmexCD-toprJ in bacteria using CRISPR/Cas9\" [International Journal of Antimicrobial Agents 65 (2025) 107390].","authors":"Lei Xu, Xiaoyu Lu, Yan Li, Patrick Butaye, Shangshang Qin, Zhiqiang Wang, Ruichao Li","doi":"10.1016/j.ijantimicag.2026.108017","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2026.108017","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"108017"},"PeriodicalIF":5.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193248","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":"AI strategies to combat antimicrobial resistance.","authors":"Jiawei Wang, Adrian Cazares","doi":"10.1016/j.ijantimicag.2026.108037","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2026.108037","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"108037"},"PeriodicalIF":5.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181639","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":"Vancomycin Population Pharmacokinetics and Exposure Variability in Children with Multiple Organ Dysfunction Syndrome.","authors":"Marc H Scheetz, Justin Shiau, Victor Amajor, Amanda Bwint, Anna Sharova, Josey Hensley, Steven L Shein, Janet R Hume, Courtney M Rowan, Carolina Quintana Grijalba, Matthew P Malone, Erin K Stenson, Scott L Weiss, Matt S Zinter, Sujatha Kannan, Mary K Dahmer, Ryan Nofziger, Nathaniel J Rhodes, Athena F Zuppa, Manjunath P Pai, Mark W Hall, Kevin J Downes","doi":"10.1016/j.ijantimicag.2026.108035","DOIUrl":"10.1016/j.ijantimicag.2026.108035","url":null,"abstract":"<p><p>In children with multiple organ dysfunction syndrome (MODS), vancomycin dosing is frequently guided by population-based approaches followed by therapeutic drug monitoring that requires considerable blood volumes. We sought to develop a population pharmacokinetic (PK) model and describe vancomycin exposures using blood-sparing, whole-blood volumetric absorptive microsampling (VAMS). In this multicentre prospective observational study, up to 15 PK samples were collected per subject over 3 days. Individual whole-blood areas under the concentration-time curve during 0-24 hours (AUC_0-24h) and 24-48 hours (AUC_24-48h) after treatment initiation were estimated. Simulations explored exposures across weight and renal function strata. Sixty-five subjects were included in the final model cohort (median age, 10 years [range, 1 month-17 years]; median weight, 30 kg [3-214 kg]). A two-compartment, allometrically scaled model incorporating renal function best described vancomycin PK. The median dose preceding the first PK sample was 380 mg (15 mg/kg), with most subjects receiving vancomycin every 6 hours. In the fully paired analysis set (n=46), median whole-blood AUC_0-24h and AUC_24-48h were 475 mg·h/L (range, 232-1,749) and 594 mg·h/L (range, 188-2,157), respectively. Simulations demonstrated substantial exposure variability across weight and renal function strata. These findings demonstrate substantial interindividual exposure variability despite population-based dosing. The model provides a foundation for prospective evaluation of individualized exposure estimation using sparse VAMS sampling. Whole-blood VAMS AUC therapeutic targets remain unvalidated, and direct interpretation against established plasma-based targets is an important future effort.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"108035"},"PeriodicalIF":5.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181619","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":"Concentration and penetration of nemonoxacin in bronchopulmonary tissues of patients undergoing pulmonary surgery: an observational PK study.","authors":"Jinjin Zhao, Yongjun Zhu, Xin Li, Xiaoyong Xu, Jufang Wu, Haijing Yang, Fengjia Zhu, Jing Chen, Yuancheng Chen, Yi Li, Yaxin Fan, Beining Guo, Zhiming Chen, Jing Zhang","doi":"10.1016/j.ijantimicag.2026.108034","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2026.108034","url":null,"abstract":"<p><strong>Background: </strong>Nemonoxacin is a novel nonfluorinated quinolone with broad-spectrum antibacterial activity. It is indicated for the treatment of community-acquired pneumonia (CAP). This study was designed to characterize the pharmacokinetics (PK) and penetration of nemonoxacin in human bronchopulmonary tissues.</p><p><strong>Methods: </strong>Forty patients undergoing pulmonary surgery were enrolled and randomly assigned to one of the five groups according to the predefined timepoints of sampling. All patients received oral 500 mg nemonoxacin once daily for 3-5 consecutive days before surgery. Blood, lung tissue, bronchial mucosa, bronchial secretion, and bronchial cartilage samples were collected during surgery at 3 ± 1, 5 ± 1, 9 ± 1, 12 ± 2, or 24 ± 4 h following the last nemonoxacin dose. Nemonoxacin concentrations were determined and steady state PK profiles were calculated.</p><p><strong>Results: </strong>Nemonoxacin reached higher concentrations in lung tissues, bronchial mucosa, and bronchial secretions than in plasma. The tissue-to-plasma 24-h exposure ratio in lung tissue, bronchial mucosa, bronchial secretion, and bronchial cartilage was 4.15, 3.61, 2.13, and 0.62, respectively. The fAUC_0-24/MIC in plasma, lung tissue, and bronchial mucosa against Streptococcus pneumoniae was 154.22, 640.45, and 556.82, respectively, which were much higher than the PK/PD targets. These results indicate that nemonoxacin has sufficient bronchopulmonary penetration for an antibacterial effect following multiple oral 500 mg doses in patients undergoing pulmonary surgery. Oral nemonoxacin 500 mg once daily is expected to achieve sufficient microbiological efficacy for CAP caused by S. pneumoniae.</p><p><strong>Conclusion: </strong>The findings in this study further justify the recommended dosing regimen of nemonoxacin for CAP.</p><p><strong>Trial registration: </strong>This study was registered at www.chictr.org.cn (identifier ChiCTR1900022591).</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"108034"},"PeriodicalIF":5.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181642","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":"Advancing bacteriophage therapy through encapsulation: An evidence-based scoping review from animal trials.","authors":"Ismail Hossain, Sam Abraham, Jasim M Uddin","doi":"10.1016/j.ijantimicag.2026.108032","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2026.108032","url":null,"abstract":"<p><strong>Background: </strong>The escalating threat of antimicrobial resistance has renewed interest in bacteriophage (phage) therapy, with encapsulation emerging as a promising strategy to enhance phage stability, bioavailability and targeted delivery.</p><p><strong>Objectives: </strong>To comprehensively map and synthesize the available in vivo evidence on encapsulated phage therapy and identify translational gaps relevant to clinical advancement.</p><p><strong>Methods: </strong>Following PRISMA-ScR guidelines, we systematically searched Web of Science Core Collection, Cochrane Central, PubMed, MEDLINE (Ovid), and Scopus.</p><p><strong>Results: </strong>Across 56 included studies, research output was concentrated in Asia, particularly India and China. Ionotropic gelation and alginate-based carriers were the most frequently used encapsulation strategies. Oral/gavage administration was the predominant route of phage delivery, with mice and chickens representing the most frequently used animal models. Encapsulated phage demonstrated high encapsulation efficiency, improved survival in simulated gastric fluid, and efficient release in simulated intestinal fluid, with significant therapeutic outcomes reported in 94.6% (53/56) of in vivo studies.</p><p><strong>Conclusion: </strong>Encapsulated phage therapy shows promising preclinical efficacy, but translational gaps remain. Future research should prioritize large-animal models, long-term studies, and standardized, scalable encapsulation approaches to support clinical translation and regulatory advancement.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"108032"},"PeriodicalIF":5.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127400","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":"Antibacterial dose optimization in patients with febrile neutropenia: Are we targeting the right patients and the right endpoints?","authors":"João Paulo Telles, Birgit Koch","doi":"10.1016/j.ijantimicag.2026.108024","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2026.108024","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"108024"},"PeriodicalIF":5.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109152","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":"Vancomycin treatment outcomes and machine learning-based identification of heterogeneous vancomycin-intermediate Staphylococcus aureus infections.","authors":"Yaxin Fan, Lin Xi, Ping Yang, Hailan Wu, Nanyang Li, Qiyu Bian, Huajun Zheng, Yongqiang Zhu, Jufang Wu, Beining Guo, Jing Zhang","doi":"10.1016/j.ijantimicag.2026.108021","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2026.108021","url":null,"abstract":"<p><strong>Objectives: </strong>Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections remain underdiagnosed with unclear clinical impact. This multicenter study evaluated vancomycin treatment outcomes and developed a machine learning (ML)-based diagnostic model.</p><p><strong>Methods: </strong>We prospectively enrolled 200 patients with MRSA infections from 20 Chinese hospitals between February 2012 and July 2021. Population analysis profile-area under the curve (PAP-AUC) testing was performed on frozen isolates to confirm hVISA phenotype, and confirmed strains underwent whole-genome sequencing. Vancomycin therapeutic drug monitoring and pharmacokinetic/pharmacodynamic (PK/PD) analysis was performed. A ML model was developed for hVISA prediction.</p><p><strong>Results: </strong>Of 200 MRSA-infected patients, 117 (58.5%) were identified with hVISA infections, including 98 (98/175, 56.0%) adults and 19 (19/25, 76.0%) pediatric patients. Despite higher vancomycin doses, adult patients with hVISA infection achieved lower PK/PD indices than vancomycin-susceptible S. aureus (VSSA). In adults receiving vancomycin monotherapy, hVISA infection was associated with significantly higher treatment failure than VSSA infection (34.6% vs. 5.0%, P = 0.028). The predominant hVISA clones were ST5, ST239 and ST764, with ST5 and ST239 showing higher treatment failure rates than ST764. Among 10 ML models, LASSO-logistic regression performed best with AUC of 0.834 (95% CI 0.711-0.930) on test set, identifying vancomycin MIC, tracheal intubation, and prior penicillin use as key predictors.</p><p><strong>Conclusions: </strong>High prevalence of hVISA among MRSA isolates and its impact on vancomycin monotherapy warrant early identification. The ML model enables identification of high-risk patients, supporting a shift toward phenotype- and sequence type-guided personalized dosing.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"108021"},"PeriodicalIF":5.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109189","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 \"Isavuconazole prophylaxis and treatment in pediatric HSCT recipients: Pharmacokinetics, safety, and efficacy\".","authors":"Ercan Yılmaz, Nezihe Koker Özer, Erdem Topal","doi":"10.1016/j.ijantimicag.2026.108033","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2026.108033","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"108033"},"PeriodicalIF":5.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109120","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 'Stepwise within-host evolution of a bla_CTX-M-27-positive Klebsiella pneumoniae clone under changing antimicrobial pressures leading to enhancement of β-lactam resistance'.","authors":"Masamune Aihara, Yasuhiro Gotoh, Keiji Nakamura, Tomoko Kimura-Hyoda, Yuya Kunisaki, Tetsuya Hayashi","doi":"10.1016/j.ijantimicag.2026.108031","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2026.108031","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"108031"},"PeriodicalIF":5.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109137","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}