International Journal of Antimicrobial Agents最新文献

{"title":"Fluconazole exposure during mechanical circulatory support (MCS) device insertion","authors":"Kelly A. Cairns ,&nbsp;Kate Morton ,&nbsp;Trisha N. Peel ,&nbsp;Iain J. Abbott ,&nbsp;David M. Kaye ,&nbsp;Silvana Marasco ,&nbsp;Andrew A. Udy ,&nbsp;David Daly ,&nbsp;Victoria Warner ,&nbsp;Anna Coldham ,&nbsp;Jeffrey D. Pope ,&nbsp;Hans G. Schneider ,&nbsp;Michael J. Dooley","doi":"10.1016/j.ijantimicag.2025.107647","DOIUrl":"10.1016/j.ijantimicag.2025.107647","url":null,"abstract":"<div><h3>Objective</h3><div>Mechanical circulatory support (MCS) devices are an important intervention for patients with advanced heart failure. Invasive <em>Candida</em> spp. infections following MCS device insertion have been reported. The addition of fluconazole to surgical prophylaxis regimens is controversial, and there is a lack of data describing exposures achieved during MCS device insertion.</div></div><div><h3>Methods</h3><div>A pilot pharmacokinetic study was undertaken to determine the plasma fluconazole exposure achieved during MCS device insertion. Perioperative fluconazole levels were drawn at four time points during the MCS device insertion surgery: knife to skin, start of cardiac bypass, end of cardiac bypass, and at the time of skin closure. A secondary outcome was to determine the <em>Candida</em> spp. colonization patterns in this patient cohort.</div></div><div><h3>Results</h3><div>Forty perioperative plasma fluconazole concentrations (from 10 patients) were available for analysis. One patient received 400 mg IV fluconazole preoperatively, and the remainder received 200 mg IV. The median measured concentration at knife to skin, start of cardiac bypass, end of cardiac bypass, and skin closure, was 3.85 mg/L (IQR: 3.53–4.48 mg/L), 3.75 mg/L (IQR: 3.45–4.23 mg/L), 3.45 mg/L (IQR: 3.08–3.75 mg/L), and 3.35 mg/L (IQR: 2.93–3.55 mg/L), respectively. Preoperative <em>Candida</em> colonization swabs isolated <em>Candida parapsilosis</em> (<em>n</em> = 2), <em>Candida glabrata</em> (<em>n</em> = 2), and <em>Candida albicans</em> (<em>n</em> = 1). A single postoperative swab was positive for <em>C. glabrata.</em></div></div><div><h3>Conclusion</h3><div>In 10 patients undergoing MCS device insertion, fluconazole 200 to 400 mg IV achieved median plasma levels of between 3 and 4 mg/L throughout the surgical procedure but may not adequately cover for <em>C. glabrata</em>.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107647"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345074","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":"2026-01-01","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":"Combined disk-based tests for phenotypic identification of KPC variants in Enterobacterales","authors":"Feng Yang ,&nbsp;Li Ding ,&nbsp;Siquan Shen ,&nbsp;Chengkang Tang ,&nbsp;Weiwei Yang ,&nbsp;Qingyu Shi ,&nbsp;Renru Han ,&nbsp;Dandan Yin ,&nbsp;Yan Guo ,&nbsp;Fupin Hu","doi":"10.1016/j.ijantimicag.2025.107663","DOIUrl":"10.1016/j.ijantimicag.2025.107663","url":null,"abstract":"<div><h3>Objective</h3><div>The identification of <em>Klebsiella pneumoniae</em> carbapenemase (KPC) variants is challenging due to their atypical resistance profiles, especially in resource-limited settings where molecular diagnostics are not readily available.</div></div><div><h3>Methods</h3><div>In this study, we developed a combination of disk-based phenotypic assays to identify KPC variant-positive Enterobacterales, including standard disk diffusion, the 3-aminophenylboronic acid (APB)/EDTA inhibition test, and the ESBL confirmatory test.</div></div><div><h3>Results</h3><div>In the disk diffusion test, all 18 KPC variant-producing strains analysed in this study were resistant to ceftazidime-avibactam and ertapenem, and 22.2 % (4 of 18) were resistant to imipenem, including those producing KPC-79, KPC-93, KPC-112, and KPC-157. For the APB/EDTA inhibition test, all strains were non-susceptible to meropenem (17 resistant and 1 intermediate) but showed no ≥5 mm increase in inhibition zone diameter with APB, EDTA, or both, thus yielding negative results according to criteria for wild-type carbapenemases. For the ESBL confirmatory test, four strains (producing KPC-79, KPC-93, KPC-112, and KPC-157) were negative, consistent with their imipenem resistance in disk diffusion, suggesting a potential phenotypic linkage. Based on these findings, two distinct disk-based phenotypic patterns of the KPC variants were identified. Both patterns shared resistance to ceftazidime-avibactam and ertapenem, along with a negative APB/EDTA inhibition result but differed in imipenem susceptibility and ESBL test results: one showed imipenem susceptibility with a positive ESBL test, whereas the other showed imipenem resistance with a negative ESBL test.</div></div><div><h3>Conclusions</h3><div>In conclusion, this study proposes a simple disk-based approach for the phenotypic identification of KPC variants in Enterobacterales, which may aid preliminary screening in clinical laboratories and warrants further validation.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107663"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458677","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-mediated prophage activation: Mechanisms, consequences, and therapeutic implications","authors":"Damir Gavric,&nbsp;Petar Knezevic","doi":"10.1016/j.ijantimicag.2025.107655","DOIUrl":"10.1016/j.ijantimicag.2025.107655","url":null,"abstract":"<div><h3>Objective</h3><div>Prophages, as an integral part of bacterial genomes, play a pivotal role in regulating host virulence and shaping bacterial evolution. Exposure to antibiotics, particularly those that cause DNA damage, can trigger a shift from lysogeny to the lytic cycle, i.e., initiate prophage induction.</div></div><div><h3>Methods</h3><div>This review compares the effects of various antibiotic classes on prophage induction, with particular emphasis on the associated clinical consequences.</div></div><div><h3>Results</h3><div>This process can lead to undesirable consequences, such as increased toxin production, enhanced transduction frequency, and modulation of host phenotypes and virulence traits. Among the most potent inducers are fluoroquinolones, such as ciprofloxacin, which activate stx-harbouring prophages in enterohemorrhagic <em>Escherichia coli</em> (EHEC), resulting in elevated Shiga toxin production and disease exacerbation. This effect is primarily mediated through activation of the bacterial SOS response, although other mechanisms may also contribute. Similarly, subinhibitory concentrations of certain β-lactams, sulphonamides, nitrofurans, and fosfomycin can induce prophages, although the extent of induction varies depending on the antibiotic concentration, phage type, bacterial strain, and detection methodology. The antibiotics that predominantly suppress or inhibit phage induction are aminoglycosides, some macrolides, and newer generation tetracyclines.</div></div><div><h3>Conclusions</h3><div>Further studies on antibiotic-mediated phage induction, particularly those focusing on elucidating the underlying mechanisms of this phenomenon, are necessary to maximize its beneficial effects and minimize potential adverse outcomes during therapy.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107655"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408943","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":"2026-01-01","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":"Adverse effects of posaconazole on adrenal steroid biosynthesis: An integrative approach using FAERS-based pharmacovigilance and systematic review with meta-analysis of randomised controlled trials","authors":"Yuki Nakano ,&nbsp;Kazumasa Kotake ,&nbsp;Yuki Asai ,&nbsp;Masayuki Murata ,&nbsp;Masanobu Uchiyama ,&nbsp;Nobuyuki Shimono ,&nbsp;Hirotsugu Hasuwa","doi":"10.1016/j.ijantimicag.2025.107676","DOIUrl":"10.1016/j.ijantimicag.2025.107676","url":null,"abstract":"<div><h3>Objectives</h3><div>Posaconazole, a broad-spectrum azole antifungal agent, is used for prophylaxis and treatment of invasive fungal infections. However, it has been associated with pseudoaldosteronism—a syndrome involving hypertension, hypokalaemia, and QT prolongation—likely mediated by adrenal steroid biosynthesis inhibition. This study aimed to assess the association between posaconazole and pseudoaldosteronism using a triangulated approach integrating real-world pharmacovigilance data, clinical trial evidence, and a structured causality framework.</div></div><div><h3>Methods</h3><div>A disproportionality analysis of real-world pharmacovigilance data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) was performed to detect signals for pseudoaldosteronism, hypokalaemia, hypertension, and QT prolongation. Co-reported adverse events in pseudoaldosteronism cases were identified and counted. Clinical trial evidence was synthesised through a systematic review and meta-analysis (SR/MA) of randomised controlled trials comparing posaconazole with other antifungal agents. Causality was assessed based on the Bradford Hill criteria (BHC).</div></div><div><h3>Results</h3><div>In the FAERS analysis, posaconazole and itraconazole consistently showed signals for pseudoaldosteronism. Among reports of posaconazole, 29.8% (95% confidence interval [CI]: 22.1–38.4%) of pseudoaldosteronism cases co-occurred with hypokalaemia. The MA showed that posaconazole significantly increased the risk of hypokalaemia than did voriconazole (risk ratio: 10.41; 95% CI: 2.00–54.27; <em>I²</em> = 0%). Synthesising our findings from the FAERS analysis and SR/MA supported a causal relationship based on the BHC.</div></div><div><h3>Conclusions</h3><div>This study supports a causal association between posaconazole and pseudoaldosteronism by integrating clinical data from FAERS and SR/MA. Clinicians should closely monitor serum potassium during posaconazole therapy and consider pseudoaldosteronism in patients with hypokalaemia.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107676"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145633094","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":"2026-01-01","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":"Nanomedicine for phage therapy: Encapsulation strategies for enhanced antimicrobial efficacy","authors":"Alexis Dorta-Gorrín ,&nbsp;Verónica Salgueiriño ,&nbsp;Lorena García-Hevia","doi":"10.1016/j.ijantimicag.2025.107660","DOIUrl":"10.1016/j.ijantimicag.2025.107660","url":null,"abstract":"<div><div>Antibiotic resistance is a growing global health crisis, driving the need for alternative antimicrobial strategies. Phage therapy has re-emerged as a promising approach due to its specificity and ability to evolve against bacterial resistance mechanisms. However, therapeutic implementation is often challenged by factors such as phage stability, immune clearance, and site-specific delivery. Encapsulation technologies offer a potential solution, enhancing phage bioavailability, systemic circulation, and therapeutic action at the infection site.</div><div>This review explores the latest advancements in phage encapsulation within the context of nanomedicine-based delivery systems, including polymeric nanoparticles, liposomes, hydrogels, nanofibers, and inorganic nanoparticles. Each system is analyzed regarding its impact on phage stability, pharmacokinetics, and host-pathogen interactions, with a particular focus on applications in clinical and preclinical models of phage therapy. Liposomal and polymeric nanoparticle encapsulation enhance phage persistence in systemic circulation and protect them from degradation. Hydrogels and nanofibers improve localized phage delivery for wound healing applications, while inorganic nanoparticles and stimuli-responsive nanocarriers facilitate targeted delivery for intracellular and respiratory infections.</div><div>By leveraging nanotechnology-driven encapsulation, phage therapy can overcome key delivery challenges, expanding its potential for treating multidrug-resistant bacterial infections. This approach opens new possibilities for precision antimicrobial therapies, reinforcing phage therapy as a viable alternative to conventional antibiotics.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107660"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458689","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":"2026-01-01","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":"P1-like phage-plasmids drive blaCTX-M-27 transmission through lysogenic conversion and transposition","authors":"Zengfeng Zhang,&nbsp;Chunlei Shi","doi":"10.1016/j.ijantimicag.2025.107686","DOIUrl":"10.1016/j.ijantimicag.2025.107686","url":null,"abstract":"<div><h3>Objective</h3><div>P1-like phage-plasmids (PPs) are hybrid mobile genetic elements that integrate features of both P1-like phages and plasmids. This study aimed to elucidate transfer mechanisms of antimicrobial resistance gene (ARG) <em>bla</em>_CTX-M-27 mediated by P1-like PPs in <em>S</em>. Indiana.</div></div><div><h3>Methods</h3><div>Antimicrobial susceptibility testing determined the antimicrobial resistance profiles of <em>S</em>. Indiana isolates. Phylogenomic analysis inferred the evolutionary structure of P1-like PPs and P1-carrying isolates, respectively. Conjugation, lytic infection, and lysogenic conversion assays assessed the transferability, lytic activity, and lysogeny potential of P1-like PPs. Transmission electron microscopy characterized P1-like bacteriophages morphology. Transposition assays quantified the transposition frequencies of Tn<em>1722</em> derivatives, and genome walking identified insertion sites and nucleotide composition biases.</div></div><div><h3>Results</h3><div>Among 147 <em>S.</em> Indiana isolates, 9 (6.1%) carried P1 elements, including 6 with <em>bla</em>_CTX-M-27. Phylogenetic analysis indicated the secondary acquisition of <em>bla</em>_CTX-M-27 and host-specific association with P1-like PPs in <em>S.</em> Indiana. Comparative genomic showed that the P1-like PP p14076B lacked key variable phage regions but harbored a Tn<em>1722</em> derivative carrying <em>bla</em>_CTX-M-27. Despite lacking plasmid-like conjugative capability, p14076B retained the ability to infect through lysogenic conversion. Transposition assays confirmed that the Tn<em>1722</em> derivative mediated the transfer of <em>bla</em>_CTX-M-27, with AT/GC skew shifts at insertion sites, and the <em>tnpA</em> gene significantly influenced transposition frequency.</div></div><div><h3>Conclusions</h3><div>These findings highlight that the Tn<em>1722</em> derivative mediates intra-host transfer of <em>bla</em>_CTX-M-27 through transposition, while lysogenic conversion of P1-like PPs facilitates inter-species dissemination. These insights provide critical understanding of the role of P1-like PPs in the spread of ARGs.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107686"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145633132","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}