International Journal of Antimicrobial Agents最新文献

{"title":"Eliminating the tigecycline resistance RND efflux pump gene cluster tmexCD-toprJ in bacteria using CRISPR/Cas9","authors":"Lei Xu ,&nbsp;Xiaoyu Lu ,&nbsp;Yan Li ,&nbsp;Patrick Butaye ,&nbsp;Shangshang Qin ,&nbsp;Zhiqiang Wang ,&nbsp;Ruichao Li","doi":"10.1016/j.ijantimicag.2024.107390","DOIUrl":"10.1016/j.ijantimicag.2024.107390","url":null,"abstract":"<div><h3>Objectives</h3><div>Tigecycline, a last-resort antibiotic in the tetracycline class, has been effective in treating infections caused by multidrug-resistant bacteria. However, the emergence of the tigecycline resistance gene cluster <em>tmexCD-toprJ</em>, which encodes a resistance-nodulation-division efflux pump, has significantly limited its therapeutic effectiveness. This study aims to explore the potential of CRISPR/Cas9-based plasmids to target and cleave <em>tmexCD-toprJ</em> gene cluster from bacterial plasmids and chromosomal integrative conjugative elements (ICEs), respectively.</div></div><div><h3>Methods</h3><div>We developed two CRISPR/Cas9-based plasmids, pCas9Kill and pCas9KillTS. The pCas9Kill plasmid designed to eliminate <em>tmexCD-toprJ</em> from plasmids through electroporation, while the pCas9KillTS plasmid, delivered through conjugation, targeted tmexCD-toprJ within ICEs on the bacterial chromosome. The plasmid modifications were assessed using nanopore long-read sequencing.</div></div><div><h3>Results</h3><div>Electroporation with the pCas9Kill plasmid resulted in the removal of tmexCD-toprJ from plasmids, restoring bacterial susceptibility to tigecycline. Nanopore sequencing revealed that the plasmids were repaired by insertion sequences after <em>tmexCD-toprJ</em> removal. In contrast, the pCas9KillTS plasmid introduced via conjugation to target <em>tmexCD-toprJ</em> gene cluster on ICEs within the chromosome. This approach led to chromosomal cleavage and subsequent bacterial cell death.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate that both plasmids effectively inactivated <em>tmexCD-toprJ</em>, with pCas9Kill restoring tigecycline susceptibility in plasmid-bearing strains and pCas9KillTS causing targeted cell death in chromosomal ICE-harbouring bacteria. This study highlights the potential of CRISPR/Cas9 systems in addressing antibiotic resistance, providing a promising strategy to combat tigecycline-resistant pathogens.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107390"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647973","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 (CAZ-AVI) pharmacokinetics in critically ill patients undergoing continuous venovenous hemodiafiltration (CVVHDF)","authors":"Amaury O'Jeanson ,&nbsp;Konstantinos Ioannidis ,&nbsp;Elisabet I. Nielsen ,&nbsp;Lamprini Galani ,&nbsp;Aghavni Ginosyan ,&nbsp;Harry Paskalis ,&nbsp;Irena Loryan ,&nbsp;Helen Giamarellou ,&nbsp;Lena E. Friberg ,&nbsp;Ilias Karaiskos","doi":"10.1016/j.ijantimicag.2024.107394","DOIUrl":"10.1016/j.ijantimicag.2024.107394","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the pharmacokinetics (PK) of ceftazidime-avibactam (CAZ-AVI) in critically ill patients undergoing continuous venovenous hemodiafiltration (CVVHDF), and compare with a general phase III trial population.</div></div><div><h3>Methods</h3><div>A prospective PK study was conducted in critically ill patients who received CVVHDF for acute kidney injury, treated with CAZ-AVI (1000/250 mg or 2000/500 mg q8h). Plasma and CVVHDF-circuit samples were collected to determine CAZ-AVI concentrations. Individual PK parameters at steady-state were estimated using non-compartmental analysis. For visual comparison, plasma concentrations from CVVHDF patients were overlaid with simulated data from patients not receiving CVVHDF based on previously developed population PK models.</div></div><div><h3>Results</h3><div>A total of 35 plasma samples and 16 CVVHDF-circuit samples were obtained from four patients, with two patients sampled on two separate occasions. Median total clearance and volume of distribution were 4.54 L/h and 73.2 L for CAZ and 10.5 L/h and 102 L for AVI, respectively. Median contribution of CVVHDF to total clearance was 19.8% for CAZ and 5.3% for AVI. Observed CAZ-AVI PK profiles were generally within the 90% confidence interval of model predictions, but the observed concentrations were notably lower early (0–2 h) and higher later (4–8 h) in the dosing interval, suggesting a higher volume of distribution.</div></div><div><h3>Conclusions</h3><div>These results suggest that the CAZ-AVI dose regimens used in this study can be applicable in critically ill patients undergoing CVVHDF, despite the different shape of the PK profiles observed in this population. Further research with a larger patient cohort is warranted to validate and refine these findings.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107394"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710114","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":"Title Page & Editorial Board","authors":"","doi":"10.1016/S0924-8579(24)00345-5","DOIUrl":"10.1016/S0924-8579(24)00345-5","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107436"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143153843","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":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2024.107409","DOIUrl":"10.1016/j.ijantimicag.2024.107409","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107409"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143153844","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":"Safety, tolerability, and pharmacokinetics of a novel anti-influenza agent ZX-7101A tablets in healthy chinese participants: A first-in-human phase I clinical study","authors":"Junzhen Wu ,&nbsp;Qiong Wei ,&nbsp;Yi Jin ,&nbsp;Guoying Cao ,&nbsp;Jicheng Yu ,&nbsp;Xiaojie Wu ,&nbsp;Xinyi Yang ,&nbsp;Yilin Li ,&nbsp;Mei Liu ,&nbsp;Xiaoli Qin ,&nbsp;Jingwen Ai ,&nbsp;Yin Wang ,&nbsp;Wenhong Zhang ,&nbsp;Jing Zhang","doi":"10.1016/j.ijantimicag.2024.107381","DOIUrl":"10.1016/j.ijantimicag.2024.107381","url":null,"abstract":"<div><h3>Background</h3><div>We investigated the safety, tolerability, and pharmacokinetics of ZX-7101A tablets, a novel cap-dependent endonuclease inhibitor, in healthy participants in a first-in-human study.</div></div><div><h3>Methods</h3><div>The single ascending dose (SAD) part of the study included 40, 80, 160, 240, and 320 mg dose cohorts with10 participants in each dose cohort (8 participants received ZX-7101A tablets and 2 participants received placebo). The food effect (FE) part of the study was a randomised, 2-cycle, 2-way crossover design, which enrolled 16 participants to receive a single oral dose of 80 mg ZX-7101A tablets.</div></div><div><h3>Results</h3><div>ZX-7101A tablets were safe and well-tolerated in both SAD and FE studies. No participant died or experienced SAE, or withdrew prematurely. The prodrug ZX-7101A was rapidly transformed into the active ingredient ZX-7101 after a single oral dose of 40–320 mg. The blood concentration of ZX-7101A was below the lower limit of quantification at most time points. ZX-7101 reached peak concentration about 3–4 h postdose in all dose cohorts. The elimination half-life of ZX-7101 was 83.01–125.55 h, and AUC_0-24 was 1655.4–11483.7 h*ng/mL. The FE part showed that the high-fat meal significantly affected the exposure parameters compared to the fasted condition. The C_max and AUC_0-t of ZX-7101 under the fasted condition were 1.73 and 1.78 times those under the fed condition, respectively.</div></div><div><h3>Conclusions</h3><div>A single oral dose of 40 mg and 80 mg ZX-7101A tablets achieved sufficient ZX-7101 exposure for effectively inhibiting influenza A and B viruses and avian influenza viruses. These findings support 40 mg and 80 mg of ZX-7101A tablets as single dose regimens for use in phase II/III clinical trials.</div><div>This study was registered at chinadrugtrials.org.cn (identifier: CTR20212778).</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107381"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619424","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":"Novel active Trp- and Arg-rich antimicrobial peptides with high solubility and low red blood cell toxicity designed using machine learning tools","authors":"Bridget A.B. Henson,&nbsp;Fucong Li,&nbsp;José Ausencio Álvarez-Huerta,&nbsp;Poornima G. Wedamulla,&nbsp;Arianna Valdes Palacios,&nbsp;Max R.M. Scott,&nbsp;David Thiam En Lim,&nbsp;W.M. Hayden Scott,&nbsp;Monica T.L. Villanueva,&nbsp;Emily Ye,&nbsp;Suzana K. Straus","doi":"10.1016/j.ijantimicag.2024.107399","DOIUrl":"10.1016/j.ijantimicag.2024.107399","url":null,"abstract":"<div><h3>Background</h3><div>Given the rising number of multidrug-resistant (MDR) bacteria, there is a need to design synthetic antimicrobial peptides (AMPs) that are highly active, non-hemolytic, and highly soluble. Machine learning tools allow the straightforward <em>in silico</em> identification of non-hemolytic antimicrobial peptides.</div></div><div><h3>Methods</h3><div>Here, we utilized a number of these tools to rank the best peptides from two libraries comprised of: 1) a total of 8192 peptides with sequence <em>bhxxbhb</em>GAL, where <em>b</em> is the basic amino acid R or K, <em>h</em> is a hydrophobic amino acid, i.e. G, A, L, F, I, V, Y, or W and <em>x</em> is Q, S, A, or V; and 2) a total of 512 peptides with sequence RW<em>hxbh</em>RGWL, where <em>b</em> and <em>h</em> are as for the first library and <em>x</em> is Q, S, A, or G. The top 100 sequences from each library, as well as 10 peptides predicted to be active but hemolytic (for a total of 220 peptides), were SPOT synthesized and their IC₅₀ values were determined against <em>S. aureus</em> USA 300 (MRSA).</div></div><div><h3>Results</h3><div>Of these, 6 AMPs with low IC₅₀’s were characterized further in terms of: MICs against MRSA, <em>E. faecalis, K. pneumoniae, E.coli</em> and <em>P. aeruginosa</em>; RBC lysis; secondary structure in mammalian and bacterial model membranes; and activity against cancer cell lines HepG2, CHO, and PC-3.</div></div><div><h3>Conclusion</h3><div>Overall, the approach yielded a large family of active antimicrobial peptides with high solubility and low red blood cell toxicity. It also provides a framework for future designs and improved machine learning tools.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107399"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791657","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":"Epidemiology of Antimicrobial-Resistant Diarrheagenic Escherichia coli Pathotypes From Children, Livestock and Food in Dagoretti South, Nairobi Kenya","authors":"Noah O. Okumu ,&nbsp;Dishon M. Muloi ,&nbsp;Arshnee Moodley ,&nbsp;Linnet Ochien'g ,&nbsp;Julie Watson ,&nbsp;Alice Kiarie ,&nbsp;Joseph J.N. Ngeranwa ,&nbsp;Oliver Cumming ,&nbsp;Elizabeth A.J. Cook","doi":"10.1016/j.ijantimicag.2024.107419","DOIUrl":"10.1016/j.ijantimicag.2024.107419","url":null,"abstract":"<div><div>Peri-urban environments, characterized by dense human populations, cohabiting livestock, and complex food systems, serve as hotspots for food contamination and infectious diseases. Children aged 6–24 months are particularly vulnerable, as they often encounter contaminated food and water, increasing their risk of food-borne disease, with diarrhea being a common symptom. We investigated the prevalence of antimicrobial resistance (AMR) in pathogenic <em>Escherichia coli</em> from children 6–24 months of age, their food, and cohabiting livestock, in Dagoretti South subcounty in Nairobi, Kenya. Of 540 stools, 296 livestock feces, and 859 food samples collected from 585 randomly enrolled households, 16% harbored diarrheagenic <em>E. coli</em> (DEC) pathotypes. The predominant AMR phenotypes observed were trimethoprim–sulfamethoxazole, ampicillin, and tetracycline at 53%, 48% and 41%, respectively. Diarrheagenic <em>E. coli</em> from children showed significantly higher resistance to all antibiotics compared to those from livestock and food. Overall, 30% of the 274 DEC isolates from all three sources exhibited multidrug resistance. Network analysis of AMR co-occurrence revealed two clusters: (1) ampicillin, trimethoprim–sulfamethoxazole, tetracycline, amoxicillin/clavulanic acid, and chloramphenicol; and (2) nalidixic acid, ciprofloxacin, gentamicin, and ceftriaxone. The co-resistance backbone of ampicillin–trimethoprim/sulfamethoxazole–tetracycline was significantly higher among isolates from children than from other hosts (χ² = 29.858, df = 2, adjusted <em>P</em> &lt; 0.05). Logistic regression analysis revealed that on-site disposal of animal manure and garbage, along with a recent history of diarrhea, were significantly associated with AMR carriage in children (<em>P</em> &lt; 0.05). These findings emphasize the need for One Health interventions to curb emergence and spread of AMR in these close-contact populations.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107419"},"PeriodicalIF":4.9,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894252","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":"Comparing ceftazidime/avibactam and polymyxin B for treating carbapenem-resistant organisms infections: A propensity score-matched retrospective cohort study","authors":"Chunmei Liu ,&nbsp;Bing Leng ,&nbsp;Maoyu Xie ,&nbsp;Shuangyan Jiang ,&nbsp;Xiaoyan Guan ,&nbsp;Jiahui Xu ,&nbsp;Yuqing Guo ,&nbsp;Jinjiao Jiang ,&nbsp;Juan Zeng","doi":"10.1016/j.ijantimicag.2024.107418","DOIUrl":"10.1016/j.ijantimicag.2024.107418","url":null,"abstract":"<div><h3>Background and aim</h3><div>There are limited comparative studies of ceftazidime/avibactam (CAZ/AVI) vs. polymyxin B (PMB) for carbapenem-resistant organisms (CRO) infections. The aim of this study was to compare the efficacy and safety of CAZ/AVI and PMB in treating CRO infections.</div></div><div><h3>Methods</h3><div>This single-centre, retrospective cohort study with propensity score-matching (PSM) involved adult patients with CRO infections. Patients who received the CAZ/AVI-based regimen were included in the cohort group; those prescribed with the PMB-based regimen were included in the control group. The primary outcome was 28-day all-cause mortality.</div></div><div><h3>Results</h3><div>Among 298 eligible patients, 96 patients in each group were included in the PSM cohort. The CAZ/AVI group showed no improvement in 28-day or 14-day all-cause mortality, nor in 14-day clinical response, compared to the PMB group. However, the CAZ/AVI-based regimen was associated with higher 14-day clinical response rates than the PMB-based regimen in subgroups with carbapenem-resistant <em>Pseudomonas aeruginosa</em> (CRPA) infections and monotherapy. The CAZ/AVI group achieved greater CRO eradication than the PMB group (crude odds ratio [OR], 1.658; 95% confidence interval [CI], 1.108-2.480; <em>P</em> = 0.014; adjusted OR, 1.718; 95% CI, 1.055-2.798; <em>P</em> = 0.030). This advantage in CRO eradication with CAZ/AVI was consistent in most subgroups, including septic shock, bloodstream infection and lower respiratory tract infection. The CAZ/AVI and PMB groups had comparable nephrotoxicity (crude OR, 0.577; 95% CI, 0.306-1.089; <em>P</em> = 0.090; adjusted OR, 0.741; 95% CI, 0.361-1.521; <em>P</em> = 0.414).</div></div><div><h3>Conclusion</h3><div>CAZ/AVI-based and PMB-based regimens demonstrated similar clinical efficacy and nephrotoxicity in treating CRO infections. However, CAZ/AVI was superior to PMB in CRO eradication and treating CRPA infections. CAZ/AVI monotherapy was more effective than PMB monotherapy for CRO infections.</div></div><div><h3>Trial registration</h3><div>ChiCTR2300078790 prospectively registered on 19 Dec 2023 (<span><span>https://www.chictr.org.cn</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107418"},"PeriodicalIF":4.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876460","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":"Integrons are key players in the spread of beta-lactamase-encoding genes","authors":"Rafael D.S. Tavares ,&nbsp;Marta Tacão ,&nbsp;Isabel Henriques","doi":"10.1016/j.ijantimicag.2024.107421","DOIUrl":"10.1016/j.ijantimicag.2024.107421","url":null,"abstract":"<div><div>Integrons mediate the acquisition and expression of gene cassettes (GCs). The production of beta-lactamases (BLs) is the most relevant mechanism of beta-lactams resistance. To explore the role of integrons in BL genes dissemination, sequences and metadata were retrieved from the INTEGRALL database and a literature review performed. Integrons (mostly class 1) carrying ≥1 BL-encoding genes (n = 1981) were detected in 37 bacterial genera and encoded BLs from 18 families. A total of 159 BL-encoding gene cassettes (BLGCs) were identified, representing all Ambler classes, with <em>bla</em>_OXA-, <em>bla</em>_VIM- and <em>bla</em>_IMP-carrying integrons the most prevalent. <em>bla</em>_GES, <em>bla</em>_BEL and most metallo-BLs were exclusively associated with integrons. BL genes from 13 families were identified as genes captured by IS<em>CR1</em> in complex integrons (n = 234), namely <em>bla</em>_NDM, <em>bla</em>_CTX-M and <em>bla</em>_TEM. Frequently co-detected GCs encoded resistance to all major classes of antibiotics, namely aminoglycosides, phenicols and trimethoprim. Most BLGCs encoded resistance to carbapenems (n = 90) and <em>Pseudomonas aeruginosa</em> was the most frequent host. Most <em>bla</em>-carrying integrons were from clinical contexts and wastewater was the richest environmental compartment.</div><div>The frequent association of BLs and integrons indicates a significant role in dissemination of beta-lactams resistance. Considering that integrons are (<em>i</em>) low-cost structures often associated with other mobile elements, and (<em>ii</em>) often carry multiple GCs (interchangeable according to environmental <em>stimuli</em>), the association of BL genes with integrons should always be considered a risk factor for the spread of beta-lactam resistance when performing surveillance and epidemiological studies. Further studies monitoring prevalence and diversity of integrons, particularly across non-clinical environments, will draw a more comprehensive picture of integron-associated dissemination of beta-lactams resistance.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107421"},"PeriodicalIF":4.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876802","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":"Molecular Investigation of an Epidemic Dissemination of Vancomycin-Resistant Enterococcus faecium Sequence Type 80 in Guangdong Province, China","authors":"Lianghui Peng ,&nbsp;Jingjie Song ,&nbsp;Hongli Sun ,&nbsp;Xiwei Zhang ,&nbsp;Yulan Huang ,&nbsp;Shihan Zeng ,&nbsp;Zhuoyang Zhou ,&nbsp;Xiaoyan Li ,&nbsp;Chao Zhuo","doi":"10.1016/j.ijantimicag.2024.107412","DOIUrl":"10.1016/j.ijantimicag.2024.107412","url":null,"abstract":"<div><div>Background: The detection rate of vancomycin-resistant <em>Enterococcus faecium</em> (VREfm) displayed a dramatic increase in Guangdong, China, from 2021 to 2023, for which the molecular epidemiology and genomic characteristics remain largely unexplored. In this study, we investigated the genetic features and epidemiology of VREfm isolates in Guangdong.</div><div>Methods: A total of 54 Guangdong VREfm isolates were collected from three tertiary hospitals in Guangdong. We preformed antimicrobial susceptibility tests, whole genome sequencing, risk factor analysis, and bioinformatics analysis to conduct this research.</div><div>Results: Our investigation indicated that VREfm isolates were highly clonal and multidrug-resistant ST80 <em>Enterococcus faecium</em> harboring <em>van</em>A-positive plasmid. Phylogenetic analysis based on single-nucleotide polymorphisms (SNPs) demonstrated that VREfm isolates exhibited minimal genetic similarity to previously reported <em>E. faecium</em> in China, whereas they exhibited high genomic similarity to an India strain A10290 isolated in 2019 and Hiroshima isolates detected in 2020, indicative of a possible exogeneous import. The genetic environment of <em>cps</em> region showed a novel type of <em>wzy</em> gene cluster involved in capsule polysaccharide (CPS) biosynthesis flanked by ISEf1 and IS16 identified in VREfm isolates, which displayed a remarkably divergence from the downstream of putative <em>cps</em>ABCD region in other sequence types (STs) <em>E. faecium</em>. Heat map of plasmid-mediated virulence factors suggested that several predicted proteins including Cag pathogenetic island proteins existed in VREfm isolates at a high frequency.</div><div>Conclusions: This study highlighted the importance of ongoing surveillance to track the dynamic dissemination of multidrug-resistant ST80 VREfm isolates harboring multiple virulence genes in Guangdong Province, China.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107412"},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872003","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}