Journal of global antimicrobial resistance最新文献

{"title":"Unravelling the advances of CRISPR-Cas9 as a precise antimicrobial therapy: a systematic review.","authors":"Hannay Crystynah Almeida de Souza Saraiva, Pedro Panzenhagen, Anamaria Mota Pereira Dos Santos, Ana Beatriz Portes, Juliana Fidelis Dos Santos Ferreira, Carlos Adam Conte Junior","doi":"10.1016/j.jgar.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.02.002","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) is a critical public health threat, compromising treatment effectiveness. The spread of resistant pathogens, facilitated by genetic variability and horizontal gene transfer, primarily through plasmids, poses significant challenges to health systems. This review explores the potential of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology and Cas9 nucleases in combating AMR. The literature review followed the PRISMA guidelines using PubMed, Embase, and Scopus databases until July 2023. The Enterobacterales family, particularly Escherichia coli, was the main focus. The resistance genes targeted were mainly associated with β-lactam antibiotics, specifically bla genes, and colistin resistance linked to the mcr-1 gene. Plasmid vectors have been the primary delivery method for the CRISPR-Cas9 system, with conjugative plasmids resensitizing bacterial strains to various antimicrobials. Other delivery methods included electroporation, phage-mediated delivery, and nanoparticles. The efficacy of the CRISPR-Cas9 system in resensitizing bacterial strains ranged from 4.7% to 100%. Despite challenges in delivery strategies and clinical application, studies integrating nanotechnology present promising approaches to overcome these limitations. This review highlights new perspectives for the clinical use of CRISPR-Cas9 as a specific and efficient antimicrobial agent, potentially replacing traditional broad-spectrum antimicrobials in the future.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro activity of ceftolozane/tazobactam against ESBL-producing Enterobacterales in China: SMART 2016-2019 CE Level information received is 2T.","authors":"Wei Yu, Hui Zhang, Yingchun Xu, Ying Zhu, Peiyao Jia, Yue Kang, Qiwen Yang","doi":"10.1016/j.jgar.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.02.001","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the in vitro susceptibility of ESBL-producing Enterobacterales isolates to ceftolozane/tazobactam (C/T), a combination of tazobactam (a ß-lactamase inhibitor) and a new antipseudomonal cephalosporin.</p><p><strong>Methods: </strong>From 2016 to 2019, susceptibilities of 10,545 Enterobacterales isolated from intra-abdominal, urinary tract, respiratory tract and bloodstream infections to C/T and 11 other antimicrobial agents were analyzed. Non-ESBL-producing isolates were included for comparative analysis to provide a comprehensive susceptibility profile.</p><p><strong>Results: </strong>Among 10,545 isolated Enterobacterales, 54.6% were ESBL producers. The ESBL-positive rates for E. coli (984/10,545, 47.3%) and K. pneumoniae (3,606/10,545, 34.2%) were 59.8% and 51.1%, respectively. The susceptibility rate to C/T for all Enterobacterales was 79.5%. For E. coli and K. pneumoniae, the C/T susceptibilities were 89.3% and 68.0%, respectively. For non-ESBL-producing Enterobacterales, susceptibility to C/T was 99.5%. The susceptibility of non-carbapenem-resistant (CR) ESBL-producing Enterobacterales to C/T was 81.0%. The isolation rates of ESBL-positive and carbapenem-resistant Enterobacterales (CRE), CR-E. coli, and CR-K. pneumoniae were 14.3%, 5.6% and 26.8%, respectively. The susceptibility of ESBL-positive CREs to C/T was < 20% for most antimicrobials except amikacin (50.4%). The susceptibility of ESBL-positive CR-E. coli to C/T was 28.2. For ESBL-producing CR-K. pneumoniae, susceptibility to most antimicrobials was < 10%, except for amikacin (37.4%).</p><p><strong>Conclusions: </strong>The present research underscores the viability of C/T as an alternative to carbapenems for the treatment of ESBL-producing, carbapenem susceptible Enterobacterales. However, the susceptibilities of ESBL-positive CRE to C/T and other studied antimicrobials were consistently below 20%, emphasizing for new innovative treatment strategies.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First report of an Enterobacter cloacae ST837 resistant to cefiderocol co-harbouring bla_IMP-19 and mcr 4.3 resistance genes, in Italy.","authors":"Ilaria Menozzi, Erika Scaltriti, Benedetta Secci, Alessandra Dodi, Tiziana Lazzarotto, Stefano Pongolini, Claudio Foschi, Simone Ambretti","doi":"10.1016/j.jgar.2025.01.023","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.023","url":null,"abstract":"<p><strong>Objectives: </strong>We described the molecular characterization of an Enterobacter cloacae strain resistant to cefiderocol, co-harbouring bla_IMP-19 and mcr-4.3 resistance genes METHODS: The strain was isolated from the rectal swab of a 77-year-old woman during the screening for the detection of patients colonized by carbapenemase-producing Enterobacterales (CPE), in Bologna (Italy). The strain was identified at the species level by MALDI-TOF mass spectrometry and the presence of IMP carbapenemase was confirmed both by a phenotypic immunochromatographic method, and by a rapid commercial NAAT. The strain underwent an antimicrobial susceptibility testing and its genome was fully characterized to assess (i) the Multi Locus Sequence Type (MLST), (ii) the presence of antimicrobial resistance genes (AMR), (iii) the presence of virulence genes coupled with Mobile Genetic Elements.</p><p><strong>Results: </strong>MLST identified the strain as ST837. A plasmid of 60'691 bp, very similar to MW574937 plasmid of Escherichia coli was identified and carried the following AMR genes: aac(6')-II,bla_BEL-1, bla_IMP-19, msr(E), mph(E), sul1. This plasmid harboured several tra gene (traB, traC, traD, traG, traI, traJ, traKtraL, traM) of the transfer operon of E. coli conjugative F plasmid. Other AMR genes were located in the chromosome (bla_CMH-3 and fosA) or in other plasmids (bla_SHV-12 and mcr-4.3). In vitro the strain showed resistance to many beta-lactams, including cefiderocol, whereas, despite the presence of mcr-4.3 gene, it was susceptible to colistin.</p><p><strong>Conclusions: </strong>Further studies are needed to better evaluate the origin of this strain, monitoring the presence of gram-negative bacilli with a similar molecular structure in our area.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of two Nocardia brasiliensis class A β-lactamases (BRA-1 and BRS-1) and related resistance to β-lactam antibiotics.","authors":"Aimee Songo, Hervé Jacquier, Maxime Danjean, Fabrice Compain, Delphine Dorchène, Zainab Edoo, Paul-Louis Woerther, Michel Arthur, David Lebeaux","doi":"10.1016/j.jgar.2025.01.022","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.022","url":null,"abstract":"<p><strong>Objective: </strong>Molecular determinants of β-lactam resistance are poorly explored for most Nocardia species, such as Nocardia brasiliensis. In this study, we characterized resistance mediated by two β-lactamases in the reference strain N. brasiliensis HUJEG-1 and extended our analysis to nine N. brasiliensis clinical strains.</p><p><strong>Methods: </strong>The susceptibility of N. brasiliensis HUJEG-1 was determined by measuring the MIC by microdilution for five β-lactam antibiotics associated or not with β-lactamase inhibitors (clavulanate and avibactam, 4µg/mL). Two putative class A β-lactamase encoding genes (bla_BRA-1 and bla_BRS-1) were identified in the HUJEG-1 genome. Kinetic parameters of purified BRA-1 and BRS-1 were determined by spectrophotometry. Then, we extended the measurement of β-lactam resistance to nine clinical strains. These phenotypic data were compared with the genomic diversity of whole genomes (next-generation sequencing).</p><p><strong>Results: </strong>N. brasiliensis HUJEG-1 was resistant to amoxicillin, cefuroxime and cefotaxime, but susceptible to their combination with clavulanate or avibactam. This strain was resistant to imipenem (with or without inhibitors) and susceptible to meropenem. BRA-1 showed high catalytic efficiencies against penams and cephems, but not against penems, suggesting that imipenem resistance was mediated by another mechanism. The hydrolytic activity of BRS-1 was 100- to 1000-fold lower than that of BRA-1 for all β-lactams tested, suggesting that BRS-1 has a minor contribution to β-lactam resistance. Analysis of the nine clinical strains showed variations in susceptibility to cefotaxime, as well as diversity in genetic backgrounds and BRA-1 sequences.</p><p><strong>Conclusion: </strong>N. brasiliensis HUJEG-1 resistance to penams and cephems was mainly due to the class A β-lactamase BRA-1.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ibuprofen prevents the conjugative transfer of plasmid-mediated antimicrobial resistance genes.","authors":"Guangfen Zhang, Chunli Li, Xiaofan Li, Yuanyuan Li, Yunbing Li, Xiangkun Zeng, Chen Xu, Shuyan Wu, Ning Dong","doi":"10.1016/j.jgar.2025.01.012","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.012","url":null,"abstract":"<p><p>Refractory infections caused by multidrug-resistant bacteria (MDRB) pose a significant threat to public health. We reported ibuprofen inhibited the conjugation of the RP4 plasmid and plasmids from clinical strains carrying different resistance genes including mcr-1, bla_NDM, bla_KPC, tet(X4), and tmexCD1-toprJ1. Mechanistic studies suggested ibuprofen reduced ATP production and inhibited conjugation-related genes. The inhibitory effect of ibuprofen on conjugation has significant clinical implications for preventing the spread of MDR, opening new therapeutic avenues to combat MDRB.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of Acinetobacter towneri harboring a novel plasmid with bla_NDM-1 and tet(X7) from hospital wastewater in the Philippines.","authors":"Zoe Mallonga, Maho Tokuda, Rin Yamazaki, Shunta Tsuruga, Isana Nogami, Yuka Sato, Ann Gelanie Tarrayo, Rolly Fuentes, Richard Parilla, Kazuhide Kimbara, Masato Suzuki, Masaki Shintani","doi":"10.1016/j.jgar.2025.01.017","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.017","url":null,"abstract":"<p><strong>Objectives: </strong>The clinical effectiveness of carbapenem and tigecycline, which are last-resort antimicrobials used to treat multidrug-resistant bacterial infections, faces challenges due to emerging plasmid-borne resistance mechanisms, including the enzymatic inactivation of antimicrobials. Here, we investigate and report the co-occurrence of bla_NDM-1 and tet(X7) genes in an Acinetobacter towneri isolate from hospital wastewater in the Philippines.</p><p><strong>Methods: </strong>An A. towneri isolate PT23-B2 was obtained from a hospital wastewater treatment plant in Tacloban, Philippines in 2023. Whole-genome sequencing (WGS) of PT23-B2 was performed and antimicrobial resistance genes (ARGs), plasmids, and mobile genetic elements (MGEs) were detected using custom sequence databases.</p><p><strong>Results: </strong>WGS analysis of A. towneri PT23-B2 resulted in the complete genome sequence consisting of one chromosome and five putative plasmids. One of the five plasmids identified, the 134-kb plasmid named pPT23-B2_1 (of which replicon was classified as R3-T45 or GR31), contained multiple ARGs, including bla_NDM-1 and tet(X7). The bla_NDM-1 was flanked by ISAba125, and tet(X7) was associated with one IS26 family insertion sequence (IS), indicating probable transpositions into the plasmid via these MGEs. Antimicrobial susceptibility tests showed that PT23-B2 is resistant to tigecycline, in addition to meropenem.</p><p><strong>Conclusion: </strong>This is the first report on an environmental bacterial isolate from the Philippines harboring both carbapenem-resistance gene (bla_NDM-1) and tigecycline-resistance gene [tet(X7)]. This study highlights the potential dissemination of clinically important ARGs, such as bla_NDM and tet(X), in environmental reservoirs, necessitating continuous monitoring and urgent intervention strategies.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Basis of Carbapenem-Resistant Clinical Serratia marcescens in Japan.","authors":"Hazim O Khalifa, Shizuo Kayama, Mohammed Elbediwi, Liansheng Yu, Wataru Hayashi, Yo Sugawara, Mohamed-Yousif Ibrahim Mohamed, Hazem Ramadan, Ihab Habib, Tetsuya Matsumoto, Motoyuki Sugai","doi":"10.1016/j.jgar.2025.01.011","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.011","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the genetic basis of carbapenem resistance in clinical S. marcescens isolates collected from patients in Japan between 1994 and 2016. 5135 clinical isolates of S. marcescens were recovered from different medical centers across Japan, identified in central laboratories, and tested for antimicrobial agents using the broth microdilution method.</p><p><strong>Methods: </strong>All the isolates that showed intermediate or resistant phenotypes for at least one carbapenem antibiotic were confirmed by antimicrobial susceptibility testing and for carbapenemase production by the modified carbapenem inactivation method (mCIM). Furthermore, full genetic characterization with performed by whole genome sequencing for all the isolates.</p><p><strong>Results: </strong>Based on our findings, 27 isolates (0.53%) exhibited resistance to ertapenem and/or meropenem. Among these, 10 isolates were phenotypically confirmed as carbapenemase producers using the mCIM test. The isolates were resistant to a wide range of antibiotics including β-lactams (48.1% to 100%), two fluoroquinolones (77.8% to 88.9%), tigecycline and minocycline (70.4% each), and sulfamethoxazole-trimethoprim (55.6%). Whole-genome sequencing was conducted on all carbapenem-resistant strains, uncovering bla_IMP in eight isolates, comprising seven with bla_IMP-1 and one with bla_IMP-11, alongside multiple antimicrobial resistance determinants. Importantly, the phylogenomic comparison with international S. marcescens isolates revealed genetic relatedness and potential cross-border transmission events.</p><p><strong>Conclusions: </strong>Our findings underscore the importance of enhanced surveillance and infection control measures to mitigate the dissemination of multidrug-resistant pathogens, emphasizing the need for international collaboration and coordinated efforts to address antimicrobial resistance on a global scale.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial-resistant Raoultella planticola isolated from preweaned dairy calf feces.","authors":"Carlton Cannon, Seon Woo Kim, Jung-Lim Lee, Jo Ann S Van Kessel, Bradd J Haley","doi":"10.1016/j.jgar.2025.01.020","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.020","url":null,"abstract":"<p><strong>Objective: </strong>Raoultella planticola is an emerging opportunistic pathogen closely related to members of the Klebsiella genus. Genomic characterization of R. planticola isolates recovered from food animals is lacking. Here we describe the antimicrobial resistance genes, virulence factors, plasmid replicons, and phylogeny of three antimicrobial-resistant R. planticola isolates recovered from the feces of three dairy calves within 48 hours of birth.</p><p><strong>Methods: </strong>The genomes of the three R. planticola isolates were sequenced on a NextSeq 2000 platform using paired-end sequencing. The raw reads were trimmed using Trimmomatic and assembled using SPAdes v 3.15.4. Antimicrobial resistance genes, virulence factors and plasmid replicons were identified using ABRicate. Single nucleotide polymorphisms were identified among the genomes using the Harvest package and phylogenies were inferred using RAxML.</p><p><strong>Results: </strong>In total, nine different ARGs known to confer resistance to at least five different classes of antibiotics were detected among the three R. planticola genomes. These include bla_PLA, a β-lactamase found only in R. planticola, fosfomycin resistance gene fosA, and a sequence aligned with oxqAB, an efflux pump conferring resistance to antibiotics including fluoroquinolones. Each genome encoded between four and seven ARGs, with three considered genotypically to be multidrug-resistant (MDR). Two of the three genomes harbored plasmids, and all three encoded 41 to 42 virulence factors, including iron scavenging genes sitABCD.</p><p><strong>Conclusions: </strong>Results of this study demonstrate the presence of diverse antimicrobial-resistant R. planticola, isolated from the feces of healthy dairy calves, that had some virulence factors that may cause human disease.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nationwide phylogenomic surveillance of Mycobacterium tuberculosis in Mexico reveals pathogenic and drug resistant signatures of the prevailing L4 sublineage","authors":"Ikuri Alvarez-Maya ,&nbsp;Manuel Garcia-Ulloa ,&nbsp;Armando Martinez-Guarneros ,&nbsp;Carlos A. Vazquez-Chacon ,&nbsp;Jaime Martinez-Urtaza","doi":"10.1016/j.jgar.2025.01.013","DOIUrl":"10.1016/j.jgar.2025.01.013","url":null,"abstract":"<div><h3>Background</h3><div>Tuberculosis disease is a major global health concern. In Mexico, information regarding the genomic variants of <em>Mycobacterium tuberculosis</em> (MTB) prevailing in the country and the existence of specific biogeographical patterns remains extremely scarce.</div></div><div><h3>Objective</h3><div>This study aimed to identify the genotypic patterns of MTB isolates in Mexico and determine the genes and specific single nucleotide polymorphisms involved in the evolution of these populations.</div></div><div><h3>Methods</h3><div>Phylogenomic and pan-genomic analyses were performed using publicly available Mexican MTB genomes along with 33 newly sequenced genomes from Jalisco, considering a global context.</div></div><div><h3>Results</h3><div>The L4 sublineages of MTB, such as L4.1.1 (X), L4.1.2 (H), and L4.3 (LAM), were the most prevalent in Mexico. We found exclusive mutations and gene clusters in a virulent sublineage L4.1.1.3 (X3), which is endemic to Mexico. These genes encoded three PE/PPE family proteins: a multidrug transporter, thioredoxin domain-containing protein, quinone-dependent <span>l</span>-lactate dehydrogenase, DUF1725 domain-containing protein, amidase, poly (A) polymerase, and six hypothetical/uncharacterised proteins. Additionally, the genes encode an ESX-1 secretion-associated protein and a deazaflavin-dependent nitroreductase (<em>ddn</em>).</div></div><div><h3>Conclusion</h3><div>X3 was distinguished from the rest of the sublineages by containing genes related to pathogenicity and virulence, as well as a gene linked to delamanid, an antibiotic for active multidrug-resistant tuberculosis. These findings provide valuable insight into the circulation and spread of MTB in Mexico.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"41 ","pages":"Pages 224-232"},"PeriodicalIF":3.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imipenem/Cilastatin encapsulation in UIO-66-NH₂ carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolates.","authors":"Shakila Baei Lashaki, Pooria Moulavi, Fatemeh Ashrafi, Aram Sharifi, Sepideh Asadi","doi":"10.1016/j.jgar.2025.01.010","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.010","url":null,"abstract":"<p><strong>Background: </strong>This study aims to investigate the effectiveness of UIO-66-NH₂, a metal-organic framework (MOF), as a carrier for imipenem/cilastatin (Imp/Cil) in overcoming resistance in clinical isolates of imipenem-resistant Pseudomonas aeruginosa.</p><p><strong>Methods: </strong>The UIO-66-NH₂-Imp/Cil formulations were synthesized and characterized using dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Drug entrapment efficiency of UIO-66-NH₂-Imp/Cil, and Imp/Cil release rates were determined. The stability of formulations was assessed by at room temperature and refrigeration for two months. The antibacterial, anti-biofilm and anti-virulence activities of formulations were investigated against imipenem-resistant Pseudomonas aeruginosa isolates.</p><p><strong>Results: </strong>The UIO-66-NH₂-Imp/Cil formulation showed an average particle size of 212.3 ± 7.3 nm, a polydispersity index (PDI) of 0.142 ± 0.010, and an entrapment efficiency (EE%) of 74.19 ± 1.12%. Drug release from the formulation followed a Korsmeyer-Peppas kinetic model, with 52% of the drug released over 72 hours. Antibacterial testing indicated a significant decrease in minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the UIO-66-NH₂-Imp/Cil formulation compared to free Imp/Cil, demonstrating enhanced antibacterial activity. Furthermore, the anti-biofilm and anti-virulence activity of UIO-66-NH₂-Imp/Cil was confirmed by the reduction of bacterial hemolysis activity, minimal pyocyanin, EPS (extracellular polymeric substance) production, and lower metabolic activity of pathogens. Also, UIO-66-NH₂-Imp/Cil causes significant reduction in the expression of lasA, lasB and, rhlA genes, which resulted in the inhibition of quorum-sensing (QS) system activity.</p><p><strong>Conclusion: </strong>These findings indicate that UIO-66-NH₂-Imp/Cil nanocarriers offer a promising new approach against multidrug-resistant Gram-negative pathogens, providing insights into potential mechanisms of antimicrobial action.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}