{"title":"Pseudomonas aeruginosa epidemic high-risk clones and their association with multidrug-resistant","authors":"","doi":"10.1016/j.jgar.2024.07.003","DOIUrl":"10.1016/j.jgar.2024.07.003","url":null,"abstract":"<div><h3>Objective</h3><p>In Ecuador, data on molecular epidemiology, as well as circulating clones, are limited. Therefore, this study aims to know the population structure of <em>Pseudomonas aeruginosa</em> by identifying clones in clinical samples in Quito-Ecuador.</p></div><div><h3>Methods</h3><p>A significant set (45) clinical <em>P. aeruginosa</em> isolates were selected, including multidrug and non-multidrug resistant isolates, which were assigned to sequence types (STs) and compared with their antibiotic susceptibility profile. The genetic diversity was assessed by applying the multilocus sequence typing (MLST) scheme and the genetic relationships between different STs were corroborated by phylogenetic networks.</p></div><div><h3>Results</h3><p>The MLST analysis identified 24 different STs and the most prevalent STs were ST-3750 and ST-253. The majority of the multidrug-resistance (MDR) isolates were included in ST-3750 and ST-253, also 3 singleton STs were identified as MDR isolates. The 21 different STs were found in non-multidrug resistance (non-MDR) isolates, and only 3 STs were found in more the one isolate.</p></div><div><h3>Conclusions</h3><p>The population structure of clinical <em>P. aeruginosa</em> present in these isolates indicates a significant association between MDR isolates and the clonal types: all ST-3750 and ST-253 isolates were MDR. ST-3750 is a closely related strain to the clonal complex ST111 (CC111). ST-253 and ST111 are a group of successful high-risk clones widely distributed worldwide. The multiresistant isolates studied are grouped in the most prevalent STs found, and the susceptible isolates correspond mainly with singleton STs. Therefore, these high-risk clones and their association with MDR phenotypes are contributing to the spread of MDR in Quito, Ecuador.</p></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213716524001309/pdfft?md5=3b58ad5e6062fb8d5645e15ef495d76b&pid=1-s2.0-S2213716524001309-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633739","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":"Prevalence and characterization of an integrative and conjugative element carrying tet(X) gene in Elizabethkingia meningoseptica","authors":"","doi":"10.1016/j.jgar.2024.07.001","DOIUrl":"10.1016/j.jgar.2024.07.001","url":null,"abstract":"<div><h3>Objectives</h3><p>To investigate the <em>tet</em>(X) gene, a determinant of tigecycline resistance, in the emerging pathogen <em>Elizabethkingia meningoseptica</em> and its association with an integrative and conjugative element (ICE).</p></div><div><h3>Methods</h3><p><em>All E. meningoseptica</em> genomes from the National Center for Biotechnology Information (<em>n</em> = 87) were retrieved and annotated for resistome searches using the CARD database. A phylogenic analysis was performed based on the <em>E. meningoseptica</em> core genome<em>.</em> The ICE was identified through comparative genomics with other ICEs occurring in <em>Elizabethkingia</em> spp.</p></div><div><h3>Results</h3><p>Phylogenetic analysis revealed <em>E. meningoseptica</em> genomes from six countries distributed across different lineages, some of which persisted for years. The common resistome of these genomes included <em>bla</em><sub>BlaB</sub>, <em>bla</em><sub>CME</sub>, <em>bla</em><sub>GOB</sub>, <em>ran</em>A/B, <em>aad</em>S, and <em>cat</em>B (genes associated with resistance to β-lactams, aminoglycosides, and chloramphenicol). Some genomes also presented additional resistance genes (<em>dfr</em>A, <em>ere</em>D, <em>bla</em><sub>VEB</sub>, <em>aad</em>S, and <em>tet</em>(X)). Interestingly, <em>tet</em>(X) and <em>aad</em>S were located in an ICE of 49 769 bp (ICEEmSQ101), which was fully obtained from the <em>E. meningoseptica</em> SQ101 genome. We also showed evidence that the other 27 genomes harboured this ICE. The distribution of ICEEmSQ101, carrying <em>tet</em>(X), was restricted to a single Chinese lineage.</p></div><div><h3>Conclusions</h3><p>The <em>tet</em>(X) gene is not prevalent in the species <em>E. meningoseptica</em>, as previously stated for the genus <em>Elizabethkingia</em>, since it is present only in a single Chinese lineage. We identified that several <em>E. meningoseptica</em> genomes harboured an ICE that mobilized the <em>Elizabethkingia tet</em>(X) gene and exhibited characteristics similar to the ICEs of other <em>Flavobacteria</em>, which would favour their transmission in this bacterial family.</p></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213716524001322/pdfft?md5=92abea5f89a5b94615fef94dba806c60&pid=1-s2.0-S2213716524001322-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616623","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":"Genetic elements harbouring oxazolidinone resistance genes detected in swine enterococci circulate in clinical isolates, Italy","authors":"","doi":"10.1016/j.jgar.2024.06.016","DOIUrl":"10.1016/j.jgar.2024.06.016","url":null,"abstract":"","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213716524001292/pdfft?md5=1a543ced99be3ea382d3780d3d8a7b5e&pid=1-s2.0-S2213716524001292-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616622","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":"Characteristics of multidrug-resistant hypervirulent Klebsiella pneumoniae strains ST29 and K212 harbouring tmexC2-tmexD2-toprJ2","authors":"","doi":"10.1016/j.jgar.2024.06.014","DOIUrl":"10.1016/j.jgar.2024.06.014","url":null,"abstract":"<div><h3>Objectives</h3><p>This study aimed to characterize a tigecycline-resistant hypervirulent <em>Klebsiella pneumoniae</em> (HvKP) strain, identified as KLZT, which carries the tigecycline resistance gene cluster <em>tmexC2-tmexD2-toprJ2</em> belonging to ST29 and serotype K212.</p></div><div><h3>Methods</h3><p>Antimicrobial susceptibility and virulence phenotypes were assessed, followed by whole-genome sequencing (WGS) using PacBio II and MiSeq sequencers. Genome annotation was carried out using the RAST server and bioinformatics analysis revealed the genetic characteristics of this strain.</p></div><div><h3>Results</h3><p>Antimicrobial and virulence phenotype testing indicated that <em>K. pneumoniae</em> strain KLZT could be considered as a multidrug-resistant HvKP. WGS analysis showed that KLZT has a single 5,536,506-bp chromosome containing three plasmids 290,963 bp (pKLZT-1), 199,302 bp (pKLZT-2), and 4820 bp (pKLZT-3) in size, and also includes the ST29 and K212 serotypes. Four (<em>bla</em><sub>SHV-187</sub>, <em>oqxA, oqxB</em>, and <em>fosA6</em>) and six resistance genes (<em>tmexC2-tmxeD2-toprJ2, bla</em><sub>OXA-1</sub>, <em>aac(6′)-Ib-cr, catB3, arr-3</em>, and <em>bla</em><sub>LEN27</sub>) were identified from chromosomal and plasmid pKLZT-1, respectively. Gene-based analysis of the resistance genes of plasmid pKLZT-1 showed that the tigecycline resistance gene cluster-carrying region was flanked by <em>umuC</em> and <em>umuD</em> (<em>umuD</em>-<em>hps</em>-<em>IS5</em>-<em>tmexC2-tmexD2-toprJ2</em>-<em>umuC</em>), as well as other resistance genes and virulence factors (<em>ureB, ureC</em>, and <em>ureG</em>), which were carried by <em>IS5075</em>-<em>Tn3-intI1 -aac(6′)-Ib-cr-bla</em><sub>OXA-1</sub><em>-catB3-arr-3-bla</em><sub>LEN27</sub><em>-Tn3-ISkpn26-ureBCG-IS5075</em>.</p></div><div><h3>Conclusions</h3><p>WGS has revealed that a multidrug-resistant strain, HvKP KLZT, belonging to ST29 with capsular serotype K212, contains a multidrug-resistance plasmid.</p></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S221371652400122X/pdfft?md5=4ff437c688ce99f06347d0313582ae8a&pid=1-s2.0-S221371652400122X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603754","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":"Insertion with long target duplication in polymyxin B-induced resistant mutant of Salmonella","authors":"","doi":"10.1016/j.jgar.2024.07.002","DOIUrl":"10.1016/j.jgar.2024.07.002","url":null,"abstract":"<div><h3>Objectives</h3><p>A <em>Salmonella enterica</em> subsp. <em>diarizonae</em> (hereafter <em>S. diarizonae</em>) clinical strain S499 demonstrated unique genomic features. The strain S499 was treated with polymyxin B in vitro to investigate the mechanism of resistance.</p></div><div><h3>Methods</h3><p>S499 was treated with polymyxin B by increasing concentration gradually to obtain a resistant mutant S499V. Whole genomes of the two strains were sequenced using Illumina HiSeq X<strong>-</strong>10 and PacBio RS II platforms. Reverse transcription–quantitative polymerase chain reaction (RT-qPCR) was performed to compare the gene expression.</p></div><div><h3>Results</h3><p>The chromosome of strain S499 contained a 40-kb DNA region that was replicated after treatment with polymyxin B and generated a triple tandem DNA repeat region in the chromosome of mutant strain S499V. This repeat region in S499V was flanked by IS<em>1</em> and contained <em>pmrD, pmrG</em>, and <em>arnBCADTEF</em> operon<em>.</em> In comparison to the homologous 40-kb DNA region of strain S499, a few genes in the repeat DNA region of strain S499V contained truncating mutations that generate two open reading frames (ORFs). The expression of <em>pmrD, pmrG</em>, and <em>arnT</em> was significantly upregulated in S499V.</p></div><div><h3>Conclusion</h3><p>The duplication and overexpression of <em>pmrD, pmrG</em>, and <em>arnT</em> operon may be responsible for the polymyxin B resistance of mutant strain S499V.</p></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213716524001334/pdfft?md5=b614bd4747185be867b00655dbb4f751&pid=1-s2.0-S2213716524001334-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620160","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":"Colistin resistance in ESBL- and Carbapenemase-producing Escherichia coli and Klebsiella pneumoniae clinical isolates in Cambodia","authors":"","doi":"10.1016/j.jgar.2024.06.017","DOIUrl":"10.1016/j.jgar.2024.06.017","url":null,"abstract":"<div><h3>Objectives</h3><p>Despite the critical importance of colistin as a last-resort antibiotic, limited studies have investigated colistin resistance in human infections in Cambodia. This study aimed to investigate the colistin resistance and its molecular determinants among Extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing (CP) <em>Klebsiella pneumoniae</em> (<em>K. pneumoniae</em>) and <em>Escherichia coli</em> (<em>E. coli</em>) isolated in Cambodia between 2016 and 2020.</p></div><div><h3>Methods</h3><p><em>E. coli</em> (<em>n</em> = 223) and <em>K. pneumoniae</em> (<em>n</em> = 39) were tested for colistin minimum inhibitory concentration (MIC) by broth microdilution. Resistant isolates were subjected to polymerase chain reaction (PCR) for detection of mobile colistin resistance genes (<em>mcr</em>) and chromosomal mutations in the two-component system (TCS).</p></div><div><h3>Results</h3><p>Eighteen isolates (10 <em>K. pneumoniae</em> and 8 <em>E. coli</em>) revealed colistin resistance with a rate of 5.9% in <em>E. coli</em> and 34.8% in <em>K. pneumoniae</em> among ESBL isolates, and 1% in <em>E. coli</em> and 12.5% in <em>K. pneumoniae</em> among CP isolates. The resistance was associated with <em>mcr</em> variants (13/18 isolates, <em>mcr-1, mcr</em>-<em>3</em>, and <em>mcr-8.2</em>) and TCS mutations within <em>E. coli</em> and <em>K. pneumoniae</em>, with the first detection of <em>mcr-8.2</em> in Cambodia, the discovery of new mutations potentially associated to colistin resistance in the TCS of <em>E. coli</em> (PhoP I47V, PhoQ N352K, PmrB G19R, and PmrD G85R) and the co-occurrence of <em>mcr</em> genes and colistin resistance conferring TCS mutations in 11 of 18 isolates.</p></div><div><h3>Conclusions</h3><p>The findings highlight the presence of colistin resistance in ESBL- and CP- <em>Enterobacteriaceae</em> involved in human infections in Cambodia as well as chromosomal mutations in TCS and the emergence of <em>mcr</em>-<em>8.2</em> in <em>E. coli</em> and <em>K. pneumoniae</em>. It underscores the need for continuous surveillance, antimicrobial stewardship, and control measures to mitigate the spread of colistin resistance.</p></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213716524001346/pdfft?md5=baecadd2c501f3b5b9504df2e7990299&pid=1-s2.0-S2213716524001346-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616621","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":"Transmission of global clones of NDM-producing Enterobacterales and interspecies spread of IncX3 plasmid harbouring blaNDM-5 in Tokyo","authors":"","doi":"10.1016/j.jgar.2024.06.020","DOIUrl":"10.1016/j.jgar.2024.06.020","url":null,"abstract":"<div><h3>Objective</h3><p>The aim of this study is to characterise the molecular characteristics of NDM-producing <em>Enterobacterales</em>, which have been on the increase in recent years in Japan, where IMP-producing bacteria are dominant among carbapenemase-producing <em>Enterobacterales</em>.</p></div><div><h3>Methods</h3><p>We collected 21 strains of NDM-producing <em>Enterobacterales</em> detected between 2015 and 2022 at five hospitals in Tokyo and performed illumina whole genome sequencing. For the seven selected strains, nanopore long-read sequencing was also performed to characterise the plasmids harbouring <em>bla</em><sub>NDM</sub>.</p></div><div><h3>Results</h3><p>Fourteen strains were <em>Escherichia coli</em> and all carried <em>bla</em><sub>NDM-5</sub>. Among these strains, eight and three were sequence type (ST) 410 and ST167, respectively, and both groups of strains were spread clonally in different hospitals. Two strains of <em>Klebsiella pneumoniae</em> ST147 carrying <em>bla</em><sub>NDM-1</sub> were detected in a hospital, and these strains had also spread clonally. The remainder included <em>Enterobacter hormaechei, Klebsiella quasipneumoniae, Citrobacter amalonaticus</em>, and <em>Klebsiella michiganensis</em>. Plasmid analysis revealed that an identical IncX3 plasmid harbouring <em>bla</em><sub>NDM-5</sub> was shared among four strains of different bacterial species (<em>E. coli, C. amalonaticus, K. michiganensis</em>, and <em>E. hormaechei</em>) detected at the same hospital. In addition, a <em>Klebsiella quasipneumoniae</em> strain detected at a different hospital also carried an IncX3 plasmid with a similar genetic structure.</p></div><div><h3>Conclusions</h3><p>Nosocomial spread of multiple multidrug-resistant global clones and transmission of IncX3 plasmids harbouring <em>bla</em><sub>NDM-5</sub> among multiple species were detected as the major pathways of spread of NDM-producing <em>Enterobacterales</em> in Tokyo. Early detection of carriers and measures to prevent nosocomial spread are important to prevent further spread of NDM-producing organisms.</p></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213716524001310/pdfft?md5=770ef3f488ae2c9343374e33d636e4fd&pid=1-s2.0-S2213716524001310-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616624","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":"In vitro evaluation of using ceftazidime/avibactam against carbapenem-resistant Acinetobacter baumannii","authors":"","doi":"10.1016/j.jgar.2024.06.011","DOIUrl":"10.1016/j.jgar.2024.06.011","url":null,"abstract":"<div><h3>Objective</h3><p>Carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB) is a global concern as effective treatments are very limited. We previously used a modified susceptibility testing approach to predict growth suppression in carbapenem-resistant <em>Enterobacterales</em>, but there are uncertainties about the generalizability of the model. The objective of this study is to verify if a similar approach can be extended to CRAB.</p></div><div><h3>Method</h3><p>A clinical isolate of CRAB resistant to ceftazidime/avibactam (CAZ/AVI, MIC = 32/4 mg/L) was examined. CAZ susceptibility was determined using increasing concentrations of AVI (0–64 mg/L), and MIC reduction was characterized with a sigmoid inhibitory maximum effect (Emax) model. The effectiveness of CAZ/AVI was validated in a hollow fibre infection model (HFIM) over 72 hours, using simulated unbound serum / epithelial lining fluid (ELF) exposures of 2.5 g over 2 hours every 8 hours. Baseline inocula of approximately 5.5 log CFU/mL were examined.</p></div><div><h3>Results</h3><p>An AVI concentration-dependent reduction in CAZ MIC was observed (r<sup>2</sup> = 0.99). CAZ MIC was dramatically reduced from 512 mg/L (no AVI) to 32 mg/L (AVI = 4 mg/L), and further to 8 mg/L (AVI = 16 mg/L). Pharmacokinetic simulations were satisfactory in the HFIM (r<sup>2</sup> > 0.96). Bacterial suppression was observed >24 hours with the serum exposure, but not that from the ELF.</p></div><div><h3>Conclusion</h3><p>Using multiple AVI concentrations within the clinically relevant range, our susceptibility testing approach could have better insights of treatment outcome for infections caused by CRAB. This could potentially lead to effective intervention(s) overlooked by conventional susceptibility testing method. This case highlights the importance of site-specific drug exposures on determining treatment outcome.</p></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213716524001218/pdfft?md5=8babafd4c28563b4fc240c4092c9fde4&pid=1-s2.0-S2213716524001218-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600229","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":"Mutations in the pmrB gene constitute the major mechanism underlying chromosomally encoded colistin resistance in clinical Escherichia coli","authors":"","doi":"10.1016/j.jgar.2024.06.013","DOIUrl":"10.1016/j.jgar.2024.06.013","url":null,"abstract":"<div><h3>Objectives</h3><p>The mechanisms underlying chromosomally encoded colistin resistance in <em>Escherichia coli</em> remain insufficiently investigated. In this study, we investigated the contribution of various <em>pmrB</em> mutations from <em>E. coli</em> clinical isolates to colistin resistance.</p></div><div><h3>Methods</h3><p>The resistance mechanisms in eight <em>mcr</em>-negative colistin-resistant <em>E. coli</em> isolates obtained from a nationwide surveillance program in Taiwan using recombinant DNA techniques and complementary experiments were investigated. The minimal inhibitory concentrations (MICs) of colistin in the recombinant strains were compared with those in the parental strains. The expression levels of <em>pmrA</em> and <em>pmrK</em> (which are part of the <em>pmrCAB</em> and <em>pmrHFIJKLM</em> operons associated with colistin resistance) were measured using reverse transcription-quantitative real-time polymerase chain reaction.</p></div><div><h3>Results</h3><p>In the complementation experiments, various mutated <em>pmrB</em> alleles from the eight <em>mcr</em>-negative colistin-resistant <em>E. coli</em> strains were introduced into an ATCC25922 mutant with a PmrB deletion, which resulted in colistin resistance. The MIC levels of colistin in the most complemented strains were comparable to those of the parental colistin-resistant strains. Increased expression levels of <em>pmrA</em> and <em>pmrK</em> were consistently detected in most complemented strains. The impact for colistin resistance was confirmed for various novel amino acid substitutions, P94L, G19E, L194P, L98R and R27L in PmrB from the parental clinical strains. The detected amino acid substitutions are distributed in the different functional domains of PmrB.</p></div><div><h3>Conclusions</h3><p>Colistin resistance mediated by amino acid substitutions in PmrB is a major chromosomally encoded mechanism in <em>E. coli</em> of clinical origin.</p></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213716524001231/pdfft?md5=b1f5d54d4b0a2ef910c7bd7fb1e956ad&pid=1-s2.0-S2213716524001231-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600230","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":"Occurrence of multi-carbapenemase-producing Enterobacterales in a tertiary hospital in Madrid (Spain): A new epidemiologic scenario","authors":"","doi":"10.1016/j.jgar.2024.06.012","DOIUrl":"10.1016/j.jgar.2024.06.012","url":null,"abstract":"<div><h3>Introduction</h3><p>Multi-carbapenemase-producing Enterobacterales (M-CPE) are increasingly described. We characterized the M-CPE isolates prospectively recovered in our hospital (Madrid, Spain) over two years (2021–2022).</p></div><div><h3>Methods</h3><p>We collected 796 carbapenem resistant Enterobacterales (CRE) from clinical and surveillance samples. Carbapenemase production was confirmed with phenotypic (immunochromatographic, disk diffusion) and molecular (PCR, WGS) techniques. Antimicrobial susceptibility was evaluated by a standard broth microdilution method. Clinical and demographic data were collected.</p></div><div><h3>Results</h3><p>Overall, 23 M-CPE (10 <em>Klebsiella pneumoniae</em>, 6 <em>Citrobacter freundii complex, 3 Escherichia coli, 2 Klebsiella oxytoca,</em> and 2 <em>Enterobacter hormaechei</em>) isolates were recovered from 17 patients (3% with CPE, 0.26-0.28 cases per 1000 admissions). OXA-48 + KPC-3 (7/23) and KPC-3 + VIM-1 (5/23) were the most frequent carbapenemase combinations. All patients had prior antibiotics exposure, including carbapenems (8/17). High resistance rates to ceftazidime/avibactam (14/23), imipenem/relebactam (16/23) and meropenem/vaborbactam (7/23) were found. Ceftazidime/avibactam + aztreonam combination was synergistic in all metallo-β-lactamase producers. Clonal and non-clonal related isolates were found, particularly in <em>K. pneumoniae</em> (5 ST29, 3 ST147, 3 ST307) and <em>C. freundii</em> (3 ST8, 2 ST125, 1 ST563). NDM-1 + OXA-48 was introduced with the ST147-<em>K. pneumoniae</em> high-risk clone linked to the transfer of a Ukrainian patient. We identified four possible nosocomial clonal transmission events between patients of the same clone with the same combination of carbapenemases (KPC-3 + VIM-1-ST29-<em>K. pneumoniae</em>, NDM-1 + OXA-48-ST147-<em>K. pneumoniae</em> and KPC-2 + VIM-1-ST145-<em>K. oxytoca</em>). Carbapenemase-encoding genes were located on different plasmids, except for VIM-1 + KPC-2-ST145-<em>K. oxytoca</em>. Cross-species transmission and a possible acquisition overtime was found, particularly between <em>K. pneumoniae</em> and <em>E. coli</em> producing OXA-48 + KPC-3.</p></div><div><h3>Conclusion</h3><p>M-CPE is an emerging threat in our hospital. Co-production of different carbapenemases, including metallo-β-lactamases, limits therapeutic options and depicts the need to reinforce infection control measures.</p></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213716524001267/pdfft?md5=32317470c5c6ad4db875d5b87dd73b91&pid=1-s2.0-S2213716524001267-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600242","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}