International Journal of Antimicrobial Agents最新文献

{"title":"Phage therapy for KPC-producing Klebsiella pneumoniae decolonization in high-risk patients: The KIDNAP Study Protocol – A prospective feasibility and proof of concept study in the Brazilian context","authors":"Iris Najjar ,&nbsp;Larissa Simão Gandolpho ,&nbsp;Jôiciglecia Pereira dos Santos ,&nbsp;Camila de Paula Siqueira ,&nbsp;Ikechukwu B. Moses ,&nbsp;Ághata Cardoso da Silva Ribeiro ,&nbsp;Mélanie Roch ,&nbsp;Roberto Sierra ,&nbsp;Diego O. Andrey ,&nbsp;Celso Arrais-Rodrigues ,&nbsp;Ana C. Gales","doi":"10.1016/j.ijantimicag.2025.107673","DOIUrl":"10.1016/j.ijantimicag.2025.107673","url":null,"abstract":"<div><h3>Background</h3><div>There has been renewed interest in phages amidst growing antimicrobial resistance. Their potential for intestinal decolonisation is interesting because of their specificity, minimal side effects, and microbiota preservation. In addition, phage-resistant bacterial mutants that arise during treatment may become more susceptible to antibiotics and less virulent, possibly leading to better clinical outcomes.</div></div><div><h3>Objectives</h3><div>This study’s primary objective is to measure the efficacy of phage-based intestinal decolonisation of <em>Klebsiella pneumoniae</em> carbapenemase (KPC)-producing <em>K. pneumoniae</em> (KPC-Kp) at 14 days post-treatment, as well as its feasibility, which is defined as &gt;80% achieving at least 7 days of treatment. Secondary objectives will include phage safety at 14 days post-treatment, intestinal KPC-Kp load changes over time, characterisation of phage-resistant KPC-Kp mutants, microbiome changes, infection-related outcomes, and general clinical outcomes 3 months after the end of treatment.</div></div><div><h3>Methods</h3><div>This feasibility and proof-of-concept study aims to include 15 high-risk patients recruited from a tertiary hospital in São Paulo who will receive individualised phage combinations for a mean duration of 14 days. Safety data will be reviewed by an independent Safety Monitoring Board. Description of microbiological techniques is provided.</div></div><div><h3>Conclusions</h3><div>To the best of our knowledge, this is the first published protocol that aims to establish a standardised, individualised phage-treatment framework for intestinal decolonisation in a high-endemic setting. It will also explore phage-bacterial interactions and their broader impact on bacterial virulence and susceptibility profiles. It represents a stepping stone towards implementing phage therapy in South America and bringing knowledge and capacities to the countries most impacted by escalating antimicrobial resistance.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107673"},"PeriodicalIF":4.6,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145581759","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":"A systematic review and meta-analysis of the global epidemiology of carbapenem-resistant Escherichia coli","authors":"Mikaela M. Walker ,&nbsp;Jason A. Roberts ,&nbsp;Yixuan Li ,&nbsp;Fekade B. Sime","doi":"10.1016/j.ijantimicag.2025.107668","DOIUrl":"10.1016/j.ijantimicag.2025.107668","url":null,"abstract":"<div><h3>Objectives</h3><div>Among drug-resistant strains, <em>Escherichia coli</em> is estimated to cause the largest number of deaths per year, globally. This study aimed to estimate the global prevalence of carbapenem-resistant <em>E. coli</em> through a systematic review and meta-analysis of the available literature.</div></div><div><h3>Methods</h3><div>Three databases, Embase, PubMed, and Scopus were screened for original research articles reporting the epidemiology of carbapenem-resistant <em>E. coli</em> between 2019 and 2023. Following data extraction, a meta-analysis was performed using the random effects model for overall prevalence and prevalence of key carbapenemase enzymes (NDM, OXA, IMP, VIM, and KPC). This systematic review was registered with PROSPERO (CRD42023433370).</div></div><div><h3>Results</h3><div>A total of 44 studies were included in this review, spanning 16 countries over five WHO regions, with a pooled global prevalence of carbapenem-resistant <em>E. coli</em> at 7 % (95 % CI 0.01; 0.31). The highest pooled prevalence was 51 % (95 % CI 43 % to 58 %) for Bangladesh, and the lowest was 0.15 % (95 % CI 0.08 % to 0.23 %) for Australia. NDM was the most frequent <em>E. coli</em> carbapenemase identified, followed by OXA, KPC, VIM, and IMP.</div></div><div><h3>Conclusions</h3><div>This study found that the prevalence of carbapenem-resistance amongst <em>E. coli</em> populations is highly variable between countries and significantly lacking in most, suggesting an increased need for robust global surveillance.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107668"},"PeriodicalIF":4.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556808","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":"Ceftazidime-avibactam resistance among clinical isolates of Citrobacter freundii, Morganella morganii, Providencia spp. and Serratia marcescens across five continents: Data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme, 2016–2023","authors":"Hao-En Jan ,&nbsp;Jiun-Ling Wang ,&nbsp;Nan-Yao Lee ,&nbsp;Shun-Chung Hsueh ,&nbsp;Yu-Tsung Huang ,&nbsp;Wen-Chien Ko ,&nbsp;Po-Ren Hsueh","doi":"10.1016/j.ijantimicag.2025.107669","DOIUrl":"10.1016/j.ijantimicag.2025.107669","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this study is to investigate the trends in ceftazidime-avibactam (CZA) resistance among clinical isolates of <em>Citrobacter freundii, Morganella morganii, Providencia</em> spp., and <em>Serratia marcescens</em> globally using the database from Antimicrobial Testing Leadership and Surveillance (ATLAS) programme, 2016–2023.</div></div><div><h3>Methods</h3><div>A total of 18,908 isolates (4,231 <em>C. freundii</em>, 4658 <em>M. morganii</em>, 3,570 <em>Providencia spp</em>., and 6449 <em>S. marcescens</em>) from five continents were analysed. Antimicrobial susceptibility testing of these isolates was conducted using the broth microdilution method.</div></div><div><h3>Results</h3><div>The CZA resistance rate was the highest in <em>Providencia</em> spp. (8.8%), followed by <em>C. freundii</em> (3.4%), <em>S. marcescens</em> (1.5%), and <em>M. morganii</em> (0.6%). An increasing resistance trend was noted in <em>C. freundii</em> (R² = 0.817) and <em>S. marcescens</em> (R² = 0.995) during the study period. The resistance rate in <em>Providencia</em> spp. peaked in 2020–2021 (R² = 0.610), while that in <em>M. morganii</em> remained sporadically low. Regionally, the biannual resistant rate of <em>C. freundii</em> rose from 6.7% to 13.0% in Asia, 0% to 7.8% in Latin America, and 0% to 7.0% in East Asia (2016–2017 vs<em>.</em> 2022–2023). Furthermore, among carbapenem-resistant isolates, CZA resistance was noted in 91.1% of <em>Providencia</em> spp., 78.8% of <em>C. freundii</em>, 34.9% of <em>S. marcescens</em>, and 60% of <em>M. morganii.</em> The predominant carbapenemase gene was <em>bla</em>_NDM in <em>Providencia</em> spp. (82.6%), <em>M. morganii</em> (69.2%), and <em>C. freundii</em> (42.0%), and <em>bla</em>_KPC in <em>S. marcescens</em> (45.3%) among carbapenemase-producing isolates.</div></div><div><h3>Conclusions</h3><div>CZA resistance is emerging across diverse Enterobacterales species, and exhibits geographic and temporal variability, and warrants continued global surveillance.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107669"},"PeriodicalIF":4.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556847","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 “Comparison of ceftazidime-avibactam with other appropriate antimicrobial therapy for the treatment of OXA-48- or KPC-producing Enterobacterales infections in Turkiye: A multi-centre retrospective matched-cohort study”","authors":"S. Dhanya Dedeepya ,&nbsp;Vaishali Goel ,&nbsp;Nivedita Nikhil Desai","doi":"10.1016/j.ijantimicag.2025.107671","DOIUrl":"10.1016/j.ijantimicag.2025.107671","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107671"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540066","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":"Impact of DNA-stored mutations on virological response in virologically suppressed PWH in the switch to modern regimens","authors":"Francesca Lombardi ,&nbsp;Elio Gentilini Cacciola ,&nbsp;Federica Carli ,&nbsp;Francesco Saladini ,&nbsp;Francesco Bassani ,&nbsp;Ilaria Vicenti ,&nbsp;William Gennari ,&nbsp;Anita Pupo ,&nbsp;Leonardo Duca ,&nbsp;Aude Christelle Ka'e ,&nbsp;Chiara Muscatiello ,&nbsp;Laura Pezzati ,&nbsp;Omar El Khalili ,&nbsp;Adarian Shallvari ,&nbsp;Valeria Micheli ,&nbsp;Antonia Bezenchek ,&nbsp;Alessandro Cozzi-Lepri ,&nbsp;Stefano Rusconi ,&nbsp;Maria Mercedes Santoro","doi":"10.1016/j.ijantimicag.2025.107670","DOIUrl":"10.1016/j.ijantimicag.2025.107670","url":null,"abstract":"<div><h3>Objective</h3><div>The clinical relevance of genotypic resistance testing (GRT) performed on viral DNA is still debated. Here, we investigate the role of archived resistance on the virological rebound (VR) after switching treatment.</div></div><div><h3>Methods</h3><div>This retrospective study enrolled virologically suppressed people with HIV (PWH) included in the ARCA database with one proviral GRT performed in the 6 months prior to the switch to a modern regimen. Baseline genotypic susceptibility scores (GSS) from HIV-1 DNA GRT (DNA-GSS) and, for a subgroup, from historical plasma GRT (hRNA-GSS) were calculated based on the switch regimen. Survival analysis was used to assess the probability and predictors of VR.</div></div><div><h3>Results</h3><div>A total of 300 PWH were analysed; 23 % of them showed full or intermediate resistance (DNA-GSS &lt;2). After the therapy switch, the overall probability of experiencing VR was 13.7 %, with PWH with DNA-GSS &lt;2 showing a higher adjusted hazard risk of VR (aHR 2.15, 95 % CI, 1.08-4.27, <em>P</em> = 0.028). Shorter time under suppression preswitch was a negative predictor of VR (per 1-year increase, aHR 0.84 95 % CI, 0.75-0.93, <em>P</em> = 0.001). In the subgroup of PWH with historical plasma GRT (<em>n</em> = 129), hRNA-GSS was not associated with VR, while PWH with an intermediate or full resistance found in both DNA-GSS and hRNA-GSS had the highest probability of experiencing VR.</div></div><div><h3>Conclusions</h3><div>Our findings evidence the role of archived resistance in predicting VR after switch therapy in suppressed PWH. Thus, proviral GRT could be a useful tool to optimise strategies for switching treatment, especially if paired with information on previous historical resistance and the duration under suppression.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107670"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540387","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":"Impact of antimicrobial resistance measures and the emergence of COVID-19 on antimicrobial use throughout the Japanese population: A retrospective cohort study using a national claims database","authors":"Ryuji Koizumi ,&nbsp;Shinya Tsuzuki ,&nbsp;Yusuke Asai ,&nbsp;Kensuke Aoyagi ,&nbsp;Norio Ohmagari","doi":"10.1016/j.ijantimicag.2025.107667","DOIUrl":"10.1016/j.ijantimicag.2025.107667","url":null,"abstract":"<div><h3>Objective</h3><div>This study examined the impact of Japan’s National Action Plan on Antimicrobial Resistance (NAP) and the COVID-19 pandemic on national trends in antimicrobial consumption (AMC) for major infectious diseases.</div></div><div><h3>Methods</h3><div>This retrospective cohort study analysed claims data for the Japanese population from 2013 to 2020. AMC was expressed as defined daily doses per 1000 inhabitants per day. The target diseases included upper respiratory infection (URI), otitis media, pneumonia, diarrhoea, urinary tract infection, skin and soft tissue infection, and sexually transmitted infection. Seasonally adjusted interrupted time-series analyses were conducted to assess the impact of NAP publication in 2016 and the COVID-19 outbreak in 2020 on the numbers of medically attended cases and antimicrobial prescription rates.</div></div><div><h3>Results</h3><div>Total AMC declined from 2016 to 2019, and decreased further in 2020. There was a significant decrease in medically attended cases in 2020 when compared to the counterfactual scenario in which COVID-19 did not occur. AMC was positively correlated with the number of medically attended cases. Total antimicrobial prescription rates decreased after NAP publication and the COVID-19 outbreak. Among the diseases, prescription rates for URI, otitis media, and pneumonia significantly decreased after both events. However, the prescription rate for diarrhoea decreased after NAP publication but increased after COVID-19. No significant trends were detected for other diseases.</div></div><div><h3>Conclusions</h3><div>Antimicrobial prescriptions for respiratory infections steadily decreased after NAP publication, which may indicate the effects of antimicrobial stewardship activities. Continued monitoring is needed to clarify the long-term effects of the COVID-19 pandemic on antimicrobial use.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107667"},"PeriodicalIF":4.6,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530588","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":"Model-informed precision pyrazinamide dosing: The establishment of a population pharmacokinetic model repository for clinical decision support","authors":"Huan Zhang ,&nbsp;Lu Han ,&nbsp;Xiao-Qin Liu ,&nbsp;Juan Wang ,&nbsp;Yi-Lin Yun ,&nbsp;Ming Zhou ,&nbsp;Zheng Jiao","doi":"10.1016/j.ijantimicag.2025.107658","DOIUrl":"10.1016/j.ijantimicag.2025.107658","url":null,"abstract":"<div><h3>Purpose</h3><div>Pyrazinamide (PZA) plays an important role in the treatment of tuberculosis (TB) and adequate PZA exposure is necessary to achieve optimal treatment outcomes. However, its pharmacokinetics exhibit marked interindividual variability. Such variability undermines the ‘one-dose-fits-all’ paradigm. Our work directly addresses this therapeutic dilemma by advancing model-informed precision dosing (MIPD) through systematic population pharmacokinetic (PPK) model evaluation.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive search of PubMed, Embase, and Web of Science to identify published PPK models and collected information on the study design, patient demographics, and final parameter estimates of these models. Based on the collected information, we used MIPD approach to establish a PZA PPK model repository and developed a web-based dashboard using R-shiny to visualize the concentration-time profile, investigate the impact of covariates on pharmacokinetic (PK), and estimate patient probability of target attainment (PTA) for a predefined dosing regimen.</div></div><div><h3>Results</h3><div>Sixteen studies conducted in adults and five studies conducted in paediatric patients were included in this model repository. Body size was identified as the most important covariate affecting the clearance of PZA. HIV/TB co-infection and pregnancy did not cause a significant change in PZA exposure; thus, no dosage adjustment was required. Moreover, to achieve the target exposure, the dosage per body weight was higher in paediatric and elderly patients with diabetes than in adults (40 mg/kg/24 h and 23 mg/kg/24 h for younger children and adults, respectively).</div></div><div><h3>Conclusions</h3><div>The developed model repository and dashboard have a broad range of potential applications in the MIPD of PZA.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107658"},"PeriodicalIF":4.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512699","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":"Discrepancy between WGS-based genotypic and phenotypic drug susceptibility testing of first and second-line drugs for Mycobacterium tuberculosis: Limited impact of unknown resistance mechanisms","authors":"Ruimin Hong ,&nbsp;Peng Xu ,&nbsp;Wenjie Lai ,&nbsp;Chi Wu ,&nbsp;Xuecong Zhang ,&nbsp;Shan Chen ,&nbsp;Dan Li ,&nbsp;Juanjia Cai ,&nbsp;Howard Takiff ,&nbsp;Jiuxin Qu ,&nbsp;Qian Gao","doi":"10.1016/j.ijantimicag.2025.107666","DOIUrl":"10.1016/j.ijantimicag.2025.107666","url":null,"abstract":"<div><h3>Objectives</h3><div>Accurate detection of <em>Mycobacterium tuberculosis</em> (MTB) drug susceptibility is critical for developing effective treatment regimens. Whole genome sequencing (WGS) based genotypic drug susceptibility testing (gDST) can comprehensively predict MTB drug resistance, but inconsistencies between gDST and phenotypic drug susceptibility tests (pDST) pose a problem for determining drug resistance.</div></div><div><h3>Methods</h3><div>To investigate the factors underlying the discrepancies, we tested 509 clinical MTB strains against nine anti-TB drugs. Minimum inhibitory concentration assays and proportional method determined pDST, while WGS-based methods – WHO catalogue (2^nd edition), TB-profiler, SAM-TB, Gen-TB and MDCNN – determined gDST.</div></div><div><h3>Results</h3><div>There were 125 discordant results between the pDST and the 2^nd edition WHO catalog-based gDST. After verifying the pDST results, 13.6% (17/125) of the discordant results could be attributed to errors in pDST. Among the remaining 108 discrepancies, 32.4% (35/108) were pDST-R/gDST-S while 67.6% (73/108) were pDST-S/gDST-R. Of the 35 pDST-R/gDST-S discordant results, 51.4% (18/35) were identified as drug resistance using other gDST tools, 28.6% (10/35) were found to be hetero-resistant, and only 20.0% (7/35) were possibly due to unknown drug resistance mechanisms. 87.7% (64/73) of inconsistent pDST-S/gDST-R results concerned ETO, EMB and STR. Based on the verified pDST results, the WHO catalogue-based gDST method has an average sensitivity of 96.8% and specificity of 98.1%.</div></div><div><h3>Conclusion</h3><div>Our results confirm that the WHO catalogue-based gDST method is a reliable alternative to pDST. Unknown drug resistance mechanisms were not the main cause of pDST-R/gDST-S; novel determinants, other than DRMs, affect drug susceptibility and may explain pDST-S/gDST-R discrepancies.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107666"},"PeriodicalIF":4.6,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503648","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":"Global genomic epidemiology of carbapenemase-producing Klebsiella pneumoniae, 1996–2023","authors":"Yuxia Shi ,&nbsp;Dongxiao Ru ,&nbsp;Minge Wang ,&nbsp;Shengliang Cao ,&nbsp;Duanduan Chen ,&nbsp;Zhenshu Si ,&nbsp;Yuxi Zhang ,&nbsp;Yubao Li ,&nbsp;Jianbiao Lu","doi":"10.1016/j.ijantimicag.2025.107657","DOIUrl":"10.1016/j.ijantimicag.2025.107657","url":null,"abstract":"<div><h3>Objectives</h3><div>Carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) has emerged as a significant global public healthchallenge.</div></div><div><h3>Methods</h3><div>A total of 63,099 KP genomes was available in the NCBI Genome database, and assembly quality was further assessed using QUAST. Antibiotic resistance genes (ARGs), virulence factors (VFs), and plasmid replicons were identified with ABRicate. Multilocus sequence typing (MLST) was performed with MLST.</div></div><div><h3>Results</h3><div>This study conducted a systematic and comprehensive global genomic analysis of 35,471 CRKP isolates collected from 101 countries from 1996 to 2023. The results showed that China (25.11%), the United States (21.63%) and the United Kingdom 101 countries from 1996 to 2023. The results showed that China (25.11%), the United States (21.63%) and the United Kingdom peaked in 2018, followed by a declining trend. Our analysis revealed that carbapenemases in CRKP were predominantly KPC (53.93%), followed by NDM (25.58%) and OXA-48-like (21.86%). The isolates were classified into 1,046 known sequence types (ST), with the most common types being ST11 (23.90%), ST258 (12.85%), ST147 (7.64%), ST15 (5.21%), and ST307 (4.03%). Notably, all CRKP isolates carried multiple ARGs, with the United States having the highest number of unique ARGs. Principal coordinate analysis (PCoA) revealed that the composition of ARGs among CRKP isolates from China differs significantly from that of isolates in other countries. Furthermore, CRKP isolates from China carried the highest number of VFs, highlighting a distinct profile compared to other regions.</div></div><div><h3>Conclusions</h3><div>This study provides comprehensive data on CRKP, underscoring the necessity for continued global surveillance to monitor the dissemination of resistance and virulence.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107657"},"PeriodicalIF":4.6,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477063","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 insight into the evolution and global transmission of tigecycline resistant tet(X4)-carrying Klebsiella species across reservoirs","authors":"Yuye Wu ,&nbsp;Yawen Yu ,&nbsp;Xueqian He ,&nbsp;Weifang Mao ,&nbsp;Qian Tong ,&nbsp;Danni Bao ,&nbsp;Huiqiong Jia ,&nbsp;Yingying Kong ,&nbsp;Yingying Zhang ,&nbsp;Mohamed S Draz ,&nbsp;João Pedro Rueda Furlan ,&nbsp;Patrick Butaye ,&nbsp;Mohamed Elhadidy ,&nbsp;Shurong Dong ,&nbsp;Zhen Cao ,&nbsp;Xinyou Xie ,&nbsp;Shengjun Wu ,&nbsp;Zhi Ruan","doi":"10.1016/j.ijantimicag.2025.107665","DOIUrl":"10.1016/j.ijantimicag.2025.107665","url":null,"abstract":"<div><h3>Objectives</h3><div>The emergence of plasmid mediated <em>tet</em>(X4) gene compromises the clinical utility of tigecycline and underscores growing concerns regarding its environmental reservoirs and potential for interspecies transmission, particularly within <em>Klebsiella</em> species. The aim of this study is to elucidate the dissemination patterns and evolutionary relationships of <em>tet</em>(X4)-harbouring plasmids across clinical and environmental <em>Klebsiella</em> isolates.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive phylogenetic analysis integrating both newly sequenced plasmids and publicly available datasets from the NCBI Plasmid database. Conjugation assays were performed to assess the horizontal transfer potential of <em>tet</em>(X4)-harbouring plasmids. Furthermore, globally sourced genomic data of <em>tet</em>(X4)-carrying <em>Klebsiella</em> strains were subjected to infer their spatiotemporal distribution, transmission dynamics, and the time to the most recent common ancestor (tMRCA) using BEAST.</div></div><div><h3>Results</h3><div>The <em>tet</em>(X4) gene was located on conjugative plasmids ranging from 5.7 kb to 19.3 kb, predominantly embedded within a conserved <em>abh-tet</em>(X4)<em>-</em>IS<em>CR2</em> structure flanked by mobile genetic elements such as IS<em>26</em> and IS<em>1</em>, which likely facilitate horizontal gene transfer and plasmid integration. These plasmids commonly co-harboured multiple ARGs, including <em>aadA1, floR</em>, and <em>tet</em>(A). The <em>tet</em>(X4)-carrying <em>Klebsiella</em> isolates exhibited substantial genetic diversity, with ST534 and ST3393 identified as the most prevalent lineages. The <em>tet</em>(X4)-carrying <em>K. pneumoniae</em> strains exhibited clonal dissemination across clinical and environmental reservoirs, with the estimated tMRCA dating back to 1873. Moreover, the co-occurrence of <em>tet</em>(X4) with carbapenemase or colistin resistance genes highlights the significant public health threat posed by these high-risk strains.</div></div><div><h3>Conclusions</h3><div>These findings highlight the urgent need for coordinated genomic surveillance under a One-Health framework to monitor and mitigate the global spread of multidrug-resistant <em>tet</em>(X4)-carrying <em>Klebsiella</em> isolates.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107665"},"PeriodicalIF":4.6,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471009","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}