Pub Date : 2025-02-19DOI: 10.1016/j.jgar.2025.01.021
Weishuai Zhai, Lu Liu, Jijun Kang, Mengjin Xiao, Yiqing Wang, Yao Wang, Yingbo Shen, Congming Wu, Jianzhong Shen, Yang Wang, Dejun Liu
Objectives: This study aimed to characterize the co-occurrence of the tigecycline resistance determinants tet(X4) and tmexCD2-toprJ2 in a Raoultella ornithinolytica isolate collected from a pig rectal swab at the slaughterhouse.
Methods: The R. ornithinolytica isolate WS60 was subjected to antimicrobial susceptibility testing. Whole-genome sequencing (WGS) was performed to analyze the genetic features of the plasmids carrying tet(X4) and tmexCD2-toprJ2. Additionally, a conjugation assay was conducted to evaluate the transferability of these plasmids, followed by a 15-day stability test to assess the persistence of the two resistance determinants.
Results: R. ornithinolytica WS60 exhibited high-level tigecycline resistance, with a minimum inhibitory concentration (MIC) of 32 μg/mL, and was also resistant to ampicillin, ampicillin-sulbactam, chloramphenicol, tetracycline, sulfamethoxazole-trimethoprim, florfenicol, and streptomycin. WGS analysis revealed that WS60 harbored three plasmids, including a 384,249-bp tmexCD2-toprJ2-carrying IncQ plasmid (pWS60-1) and a 78,159-bp tet(X4)-carrying IncFII plasmid (pWS60-2). Interestingly, pWS60-2 was identical to several plasmids found in Klebsiella spp. isolated from animals, animal-derived food, and humans. Moreover, pWS60-2 was successfully transferred to Klebsiella spp. via conjugation, whereas pWS60-1 failed to transfer. Notably, no significant fitness cost was observed in the transconjugants carrying pWS60-2. Additionally, a 15-day stability assay demonstrated that both resistance determinants were stably maintained in the bacterial population without significant loss, underscoring their persistence over time.
Conclusions: This is the first report of the co-occurrence of tet(X4) and tmexCD2-toprJ2 in R. ornithinolytica. Enhanced surveillance in slaughterhouses, along with targeted interventions, should be implemented to mitigate the potential spread of mobile tigecycline resistance throughout the food production chain.
{"title":"The co-occurrence of tet(X4) and tmexCD2-toprJ2 mediated tigecycline resistance in Raoultella ornithinolytica.","authors":"Weishuai Zhai, Lu Liu, Jijun Kang, Mengjin Xiao, Yiqing Wang, Yao Wang, Yingbo Shen, Congming Wu, Jianzhong Shen, Yang Wang, Dejun Liu","doi":"10.1016/j.jgar.2025.01.021","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.021","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to characterize the co-occurrence of the tigecycline resistance determinants tet(X4) and tmexCD2-toprJ2 in a Raoultella ornithinolytica isolate collected from a pig rectal swab at the slaughterhouse.</p><p><strong>Methods: </strong>The R. ornithinolytica isolate WS60 was subjected to antimicrobial susceptibility testing. Whole-genome sequencing (WGS) was performed to analyze the genetic features of the plasmids carrying tet(X4) and tmexCD2-toprJ2. Additionally, a conjugation assay was conducted to evaluate the transferability of these plasmids, followed by a 15-day stability test to assess the persistence of the two resistance determinants.</p><p><strong>Results: </strong>R. ornithinolytica WS60 exhibited high-level tigecycline resistance, with a minimum inhibitory concentration (MIC) of 32 μg/mL, and was also resistant to ampicillin, ampicillin-sulbactam, chloramphenicol, tetracycline, sulfamethoxazole-trimethoprim, florfenicol, and streptomycin. WGS analysis revealed that WS60 harbored three plasmids, including a 384,249-bp tmexCD2-toprJ2-carrying IncQ plasmid (pWS60-1) and a 78,159-bp tet(X4)-carrying IncFII plasmid (pWS60-2). Interestingly, pWS60-2 was identical to several plasmids found in Klebsiella spp. isolated from animals, animal-derived food, and humans. Moreover, pWS60-2 was successfully transferred to Klebsiella spp. via conjugation, whereas pWS60-1 failed to transfer. Notably, no significant fitness cost was observed in the transconjugants carrying pWS60-2. Additionally, a 15-day stability assay demonstrated that both resistance determinants were stably maintained in the bacterial population without significant loss, underscoring their persistence over time.</p><p><strong>Conclusions: </strong>This is the first report of the co-occurrence of tet(X4) and tmexCD2-toprJ2 in R. ornithinolytica. Enhanced surveillance in slaughterhouses, along with targeted interventions, should be implemented to mitigate the potential spread of mobile tigecycline resistance throughout the food production chain.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472282","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}
Pub Date : 2025-02-19DOI: 10.1016/j.jgar.2025.02.013
Anelise Stella Ballaben, Otávio G G de Almeida, Joseane Cristina Ferreira, Doroti de Oliveira Garcia, Yohei Doi, Robert K Ernst, Marcia R von Zeska Kress, Ana Lúcia da Costa Darini
Background: Serratia marcescens, an opportunistic nosocomial Gram-negative bacterium pathogen, has emerged as an important cause of healthcare-associated infections owing to its acquisition of antimicrobial resistance genes (ARGs) and virulence factor determinants.
Methods: Four carbapenem-resistant S. marcescens strains were recovered from patients admitted to different hospitals in 2017 and 2018. We assessed the antimicrobial resistance and virulence context, as well as the genetic similarities of four Brazilian S. marcescens strains, and compared the genomes of these S. marcescens isolates with whole genome data of 428 S. marcescens strains available in the NCBI Reference Sequence. Antimicrobial susceptibility testing was performed by disk diffusion and broth microdilution methods according to CLSI recommendations. Whole genome sequencing was performed using Illumina NextSeq 250-bp paired-end sequencing for two isolates, Sm424 and Sm613, which presented representative phenotypes.
Results: The pathogenicity of both sequenced strains was predicted using the Pathogen Finder tool. Both isolates carried efflux system genes (RND, SMR, MFS, ABC-family) and resistance genes (blaSTR-2, aac(6')-Ic, fos). Virulence factor genes involved in motility, regulation, capsule formation, acid resistance, and acriflavine resistance were also found. The Pathogen Finder tool predicted a >71% probability of being a human pathogen for Sm424 and Sm613.
Conclusion: S. marcescens has shown increased adaptive, resistance, and pathogenic potential, being responsible for different nosocomial infections.
{"title":"Phenotypic and in silico characterization of carbapenem-resistant Serratia marcescens clinical strains.","authors":"Anelise Stella Ballaben, Otávio G G de Almeida, Joseane Cristina Ferreira, Doroti de Oliveira Garcia, Yohei Doi, Robert K Ernst, Marcia R von Zeska Kress, Ana Lúcia da Costa Darini","doi":"10.1016/j.jgar.2025.02.013","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.02.013","url":null,"abstract":"<p><strong>Background: </strong>Serratia marcescens, an opportunistic nosocomial Gram-negative bacterium pathogen, has emerged as an important cause of healthcare-associated infections owing to its acquisition of antimicrobial resistance genes (ARGs) and virulence factor determinants.</p><p><strong>Methods: </strong>Four carbapenem-resistant S. marcescens strains were recovered from patients admitted to different hospitals in 2017 and 2018. We assessed the antimicrobial resistance and virulence context, as well as the genetic similarities of four Brazilian S. marcescens strains, and compared the genomes of these S. marcescens isolates with whole genome data of 428 S. marcescens strains available in the NCBI Reference Sequence. Antimicrobial susceptibility testing was performed by disk diffusion and broth microdilution methods according to CLSI recommendations. Whole genome sequencing was performed using Illumina NextSeq 250-bp paired-end sequencing for two isolates, Sm424 and Sm613, which presented representative phenotypes.</p><p><strong>Results: </strong>The pathogenicity of both sequenced strains was predicted using the Pathogen Finder tool. Both isolates carried efflux system genes (RND, SMR, MFS, ABC-family) and resistance genes (bla<sub>STR-2</sub>, aac(6')-Ic, fos). Virulence factor genes involved in motility, regulation, capsule formation, acid resistance, and acriflavine resistance were also found. The Pathogen Finder tool predicted a >71% probability of being a human pathogen for Sm424 and Sm613.</p><p><strong>Conclusion: </strong>S. marcescens has shown increased adaptive, resistance, and pathogenic potential, being responsible for different nosocomial infections.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472281","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}
Objectives: Staphylococcus pseudintermedius is the primary pathogen that causes pyoderma in companion animals. The increasing number of multidrug-resistant strains, including methicillin-resistant S. pseudintermedius (MRSP), has become a major concern, highlighting the need for comprehensive data on antimicrobial susceptibility. Furthermore, with advancements in the accurate identification of S. pseudintermedius in human clinical patients, it is imperative to elucidate its definitive zoonotic potential.
Methods: We analyzed 111 strains of S. pseudintermedius derived from companion animals and 21 strains of S. pseudintermedius from human clinical patients to clarify antimicrobial susceptibility and correlation between strains derived from companion animals and humans.
Results: Approximately half of the animal-derived S. pseudintermedius isolates were MRSP. The isolates, particularly MRSP, exhibited high resistance to multiple antimicrobials used to treat pyoderma. Although florfenicol and fusidic acid are not approved for the treatment of pyoderma in companion animals in Japan, their efficacy has been demonstrated. Genetic analysis revealed that ST121, ST45, and ST71 were the most common ST types in animals. Additionally, ten novel STs were identified. ST45 and ST71 have frequently been identified in companion animals abroad, suggesting potential international transmission. However, ST121 has rarely been reported outside Japan, indicating its unique evolutionary trajectory within the country. Furthermore, these sequence types were identified in strains isolated from humans. Core genome analysis revealed nearly identical genotypes, suggesting transmission from companion animals to humans.
Conclusion: A limited number of approved antimicrobials are effective against S. pseudintermedius (particularly MRSP), which is being transmitted as a zoonotic infection from companion animals to humans.
{"title":"Antimicrobial susceptibility and genetic diversity of Staphylococcus pseudintermedius isolated from companion animals and human clinical patients in Japan: potential zoonotic implications.","authors":"Masaru Usui, Rana Fahmi Sabala, Sawa Morita, Akira Fukuda, Yuzo Tsuyuki, Kae Torii, Yuka Nakamura, Koichi Okamura, Tadato Komatsu, Junpei Sasaki, Chie Nakajima, Yasuhiko Suzuki","doi":"10.1016/j.jgar.2025.02.010","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.02.010","url":null,"abstract":"<p><strong>Objectives: </strong>Staphylococcus pseudintermedius is the primary pathogen that causes pyoderma in companion animals. The increasing number of multidrug-resistant strains, including methicillin-resistant S. pseudintermedius (MRSP), has become a major concern, highlighting the need for comprehensive data on antimicrobial susceptibility. Furthermore, with advancements in the accurate identification of S. pseudintermedius in human clinical patients, it is imperative to elucidate its definitive zoonotic potential.</p><p><strong>Methods: </strong>We analyzed 111 strains of S. pseudintermedius derived from companion animals and 21 strains of S. pseudintermedius from human clinical patients to clarify antimicrobial susceptibility and correlation between strains derived from companion animals and humans.</p><p><strong>Results: </strong>Approximately half of the animal-derived S. pseudintermedius isolates were MRSP. The isolates, particularly MRSP, exhibited high resistance to multiple antimicrobials used to treat pyoderma. Although florfenicol and fusidic acid are not approved for the treatment of pyoderma in companion animals in Japan, their efficacy has been demonstrated. Genetic analysis revealed that ST121, ST45, and ST71 were the most common ST types in animals. Additionally, ten novel STs were identified. ST45 and ST71 have frequently been identified in companion animals abroad, suggesting potential international transmission. However, ST121 has rarely been reported outside Japan, indicating its unique evolutionary trajectory within the country. Furthermore, these sequence types were identified in strains isolated from humans. Core genome analysis revealed nearly identical genotypes, suggesting transmission from companion animals to humans.</p><p><strong>Conclusion: </strong>A limited number of approved antimicrobials are effective against S. pseudintermedius (particularly MRSP), which is being transmitted as a zoonotic infection from companion animals to humans.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468237","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}
Objectives: Infections caused by carbapenemase-producing Gram-negative pathogens have become a significant global public health challenge due to limited treatment options. Pathogens producing metallo-β-lactamase are particularly problematic since they are not inhibited by conventional β-lactamase inhibitors. Herein, we assess the in vitro activity of aztreonam in combination with relebactam against a collection carbapenemase producing organisms, including strains producing both serine-β-lactamase and IMP-type metallo-β-lactamase that are commonly encountered in Japan.
Methods: A total of 119 carbapenemase-producing clinical isolates were used in this study. Minimum inhibitory concentrations (MICs) of aztreonam and imipenem alone and aztreonam/relebactam, aztreonam/avibactam and imipenem/relebactam combinations were determined by the broth microdilution method.
Results: Aztreonam MICs were reduced in combination with relebactam for strains producing ESBL or AmpC in addition to IMP-type, NDM-type, GES-type or OXA-48 carbapenemases and for Stenotrophomonas spp. Additionally, aztreonam/relebactam combination MICs were significantly lower than MICs of aztreonam alone among IMP producers, NDM producers and Stenotrophomonas spp. Significant differences between aztreonam/relebactam and aztreonam MICs were also observed for strains of E. coli, K. pneumoniae and Enterobacter spp., many of which produced both metallo-β-lactamase and serine-β-lactamase. The aztreonam/relebactam combination showed comparable to higher MICs compared with the aztreonam/avibactam combination.
Conclusion: The addition of relebactam has a potential to restore the activity of aztreonam against strains that produce metallo-β-lactamase and serine-β-lactamase. The combination may have a role in the treatment of infections due to these strains in countries without access to ceftazidime-avibactam.
{"title":"In Vitro Activity of Aztreonam in Combination with Relebactam against Gram-Negative Pathogens Producing Various Serine and Metallo-β-Lactamases.","authors":"Kengo Hayashi, Masahiro Suzuki, Yoshikazu Ishii, Yasufumi Matsumura, Kazuaki Matsumoto, Sho Saito, Yohei Doi","doi":"10.1016/j.jgar.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.02.008","url":null,"abstract":"<p><strong>Objectives: </strong>Infections caused by carbapenemase-producing Gram-negative pathogens have become a significant global public health challenge due to limited treatment options. Pathogens producing metallo-β-lactamase are particularly problematic since they are not inhibited by conventional β-lactamase inhibitors. Herein, we assess the in vitro activity of aztreonam in combination with relebactam against a collection carbapenemase producing organisms, including strains producing both serine-β-lactamase and IMP-type metallo-β-lactamase that are commonly encountered in Japan.</p><p><strong>Methods: </strong>A total of 119 carbapenemase-producing clinical isolates were used in this study. Minimum inhibitory concentrations (MICs) of aztreonam and imipenem alone and aztreonam/relebactam, aztreonam/avibactam and imipenem/relebactam combinations were determined by the broth microdilution method.</p><p><strong>Results: </strong>Aztreonam MICs were reduced in combination with relebactam for strains producing ESBL or AmpC in addition to IMP-type, NDM-type, GES-type or OXA-48 carbapenemases and for Stenotrophomonas spp. Additionally, aztreonam/relebactam combination MICs were significantly lower than MICs of aztreonam alone among IMP producers, NDM producers and Stenotrophomonas spp. Significant differences between aztreonam/relebactam and aztreonam MICs were also observed for strains of E. coli, K. pneumoniae and Enterobacter spp., many of which produced both metallo-β-lactamase and serine-β-lactamase. The aztreonam/relebactam combination showed comparable to higher MICs compared with the aztreonam/avibactam combination.</p><p><strong>Conclusion: </strong>The addition of relebactam has a potential to restore the activity of aztreonam against strains that produce metallo-β-lactamase and serine-β-lactamase. The combination may have a role in the treatment of infections due to these strains in countries without access to ceftazidime-avibactam.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458101","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}
Pub Date : 2025-02-17DOI: 10.1016/j.jgar.2025.02.009
Jiawei Zhou , Xiaohua Meng , Shujun Ni , Yunxing Yang , Qiong Zhang , Lingjiao Wu , Qiong Chen
Background
This study aims to explore the phenotypic and genotypic characteristics of a plasmid that co-harbours blaIMP-4 and blaKPC-2 in a carbapenem-resistant Klebsiella pneumoniae.
Methods
Strain K194 was isolated from a 60-year-old patient. Species identification was performed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, followed by antibiotic susceptibility testing. Antimicrobial resistance genes were detected and S1-pulsed-field gel electrophoresis with Southern blot experiments were performed to identify plasmids. Whole-genome sequencing was executed with the Illumina and Oxford Nanopore platforms.
Results
K. pneumoniae K194 was resistant to multiple antibiotics, including carbapenems. This strain carried both blaIMP-4 and blaKPC-2 on a single 163 kb plasmid (pK194-P2). pK194-P2 was capable of conjugation with an efficiency of 3.4 × 10–7 in vitro conjugation experiments. Whole-genome analysis confirmed that pK194-P2 was a novel plasmid and had both IncFII- and IncN-type replicons. Sequence alignment revealed direct repeats of the sequences (GCCCAAGG) flanking a 109-kb region bounded by two copies of IS26. In vitro, evolution experiments showed that blaKPC-2 in pK194-P2 could be stably maintained in the transconjugants after 10 days of passage, while blaIMP-4 could be lost during repeated laboratory passage. Whole-genome sequencing and alignment of two blaIMP-4-negative plasmids with pK194-P2 revealed that they had a deletion of 81 or 94 kb adjacent to IS26.
Conclusions
Our study reports a novel plasmid co-harbouring blaIMP-4 and blaKPC-2 in K. pneumoniae, and highlights the potential role of IS26-mediated cointegration and deletion in plasmid formation and evolution.
{"title":"IS26-mediated cointegration generates a plasmid co-harbouring blaIMP-4 and blaKPC-2 in Klebsiella pneumoniae","authors":"Jiawei Zhou , Xiaohua Meng , Shujun Ni , Yunxing Yang , Qiong Zhang , Lingjiao Wu , Qiong Chen","doi":"10.1016/j.jgar.2025.02.009","DOIUrl":"10.1016/j.jgar.2025.02.009","url":null,"abstract":"<div><h3>Background</h3><div>This study aims to explore the phenotypic and genotypic characteristics of a plasmid that co-harbours <em>bla</em><sub>IMP-4</sub> and <em>bla</em><sub>KPC-2</sub> in a carbapenem-resistant <em>Klebsiella pneumoniae</em>.</div></div><div><h3>Methods</h3><div>Strain K194 was isolated from a 60-year-old patient. Species identification was performed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, followed by antibiotic susceptibility testing. Antimicrobial resistance genes were detected and S1-pulsed-field gel electrophoresis with Southern blot experiments were performed to identify plasmids. Whole-genome sequencing was executed with the Illumina and Oxford Nanopore platforms.</div></div><div><h3>Results</h3><div><em>K. pneumoniae</em> K194 was resistant to multiple antibiotics, including carbapenems. This strain carried both <em>bla</em><sub>IMP-4</sub> and <em>bla</em><sub>KPC-2</sub> on a single 163 kb plasmid (pK194-P2). pK194-P2 was capable of conjugation with an efficiency of 3.4 × 10<sup>–7</sup> in vitro conjugation experiments. Whole-genome analysis confirmed that pK194-P2 was a novel plasmid and had both IncFII- and IncN-type replicons. Sequence alignment revealed direct repeats of the sequences (GCCCAAGG) flanking a 109-kb region bounded by two copies of IS<em>26</em>. In vitro, evolution experiments showed that <em>bla</em><sub>KPC-2</sub> in pK194-P2 could be stably maintained in the transconjugants after 10 days of passage, while <em>bla</em><sub>IMP-4</sub> could be lost during repeated laboratory passage. Whole-genome sequencing and alignment of two <em>bla</em><sub>IMP-4</sub>-negative plasmids with pK194-P2 revealed that they had a deletion of 81 or 94 kb adjacent to IS<em>26</em>.</div></div><div><h3>Conclusions</h3><div>Our study reports a novel plasmid co-harbouring <em>bla</em><sub>IMP-4</sub> and <em>bla</em><sub>KPC-2</sub> in <em>K. pneumoniae</em>, and highlights the potential role of IS<em>26</em>-mediated cointegration and deletion in plasmid formation and evolution.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"42 ","pages":"Pages 61-65"},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458106","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}
Pub Date : 2025-02-17DOI: 10.1016/j.jgar.2025.02.006
Ronan F. O'Toole , Vitalie Covalciuc , Ana Cooke , Gaetan Thilliez , Emma K. Finlay , Kelvin W.C. Leong , Vanessa Farthing , Sebastiaan J. van Hal
Objective
High rates of resistance to vancomycin are now being reported among invasive isolates of Enterococcus faecium, a major cause of healthcare-associated infections globally. The objective of this study was to generate a better understanding of emerging vanA sequence types (ST) of the pathogen.
Methods
A temporal analysis of isolates collected from 2013 to 2020 at the Royal Prince Alfred Hospital, a large Australian hospital, was performed using genome sequencing. Relative frequencies of multi-locus ST, antibiotic resistance markers, and virulence genes were determined.
Results
ST1421 was the dominant vanA ST from 2014 to 2018. ST1424, which was not evident in the 2013 and 2014 isolates, emerged in 2016 and became the dominant vanA type in 2020 (65% of isolates). vanA ST80 was less common among the Royal Prince Alfred Hospital vanA isolates. Direct comparison of 120 genomes of each ST revealed significantly higher encoded resistance to aminocyclitols (e.g. spectinomycin) and folate-pathway antagonists (e.g. trimethoprim) in ST1421 and ST1424 compared to ST80. Furthermore, significantly higher carriage of enterococcal virulence genes ecbA (E. faecium collagen binding protein A) and hylEfm (glycosyl hydrolase) was found in ST1421 and ST1424 than in ST80.
Conclusions
Newer vanA ST ST1421 and ST1424 harboured several antibiotic resistance loci and virulence genes at significantly higher levels than those observed in ST80. Ongoing genomic surveillance is warranted for the detection of new variants of E. faecium and characterisation of their encoded resistance and virulence.
{"title":"Genomic characterisation of emerging Enterococcus faecium vanA types from 2013 to 2020 in an Australian public hospital","authors":"Ronan F. O'Toole , Vitalie Covalciuc , Ana Cooke , Gaetan Thilliez , Emma K. Finlay , Kelvin W.C. Leong , Vanessa Farthing , Sebastiaan J. van Hal","doi":"10.1016/j.jgar.2025.02.006","DOIUrl":"10.1016/j.jgar.2025.02.006","url":null,"abstract":"<div><h3>Objective</h3><div>High rates of resistance to vancomycin are now being reported among invasive isolates of <em>Enterococcus faecium</em>, a major cause of healthcare-associated infections globally. The objective of this study was to generate a better understanding of emerging <em>vanA</em> sequence types (ST) of the pathogen.</div></div><div><h3>Methods</h3><div>A temporal analysis of isolates collected from 2013 to 2020 at the Royal Prince Alfred Hospital, a large Australian hospital, was performed using genome sequencing. Relative frequencies of multi-locus ST, antibiotic resistance markers, and virulence genes were determined.</div></div><div><h3>Results</h3><div>ST1421 was the dominant <em>vanA</em> ST from 2014 to 2018. ST1424, which was not evident in the 2013 and 2014 isolates, emerged in 2016 and became the dominant <em>vanA</em> type in 2020 (65% of isolates). <em>vanA</em> ST80 was less common among the Royal Prince Alfred Hospital <em>vanA</em> isolates. Direct comparison of 120 genomes of each ST revealed significantly higher encoded resistance to aminocyclitols (e.g. spectinomycin) and folate-pathway antagonists (e.g. trimethoprim) in ST1421 and ST1424 compared to ST80. Furthermore, significantly higher carriage of enterococcal virulence genes <em>ecbA</em> (<em>E. faecium</em> collagen binding protein A) and <em>hylEfm</em> (glycosyl hydrolase) was found in ST1421 and ST1424 than in ST80.</div></div><div><h3>Conclusions</h3><div>Newer <em>vanA</em> ST ST1421 and ST1424 harboured several antibiotic resistance loci and virulence genes at significantly higher levels than those observed in ST80. Ongoing genomic surveillance is warranted for the detection of new variants of <em>E. faecium</em> and characterisation of their encoded resistance and virulence.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"42 ","pages":"Pages 42-50"},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457840","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}
Pub Date : 2025-02-13DOI: 10.1016/j.jgar.2025.02.002
Hannay Crystynah Almeida de Souza , Pedro Panzenhagen , Anamaria Mota Pereira dos Santos , Ana Beatriz Portes , Juliana Fidelis , Carlos Adam Conte-Junior
Antimicrobial resistance 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.
Objective
This review explores the potential of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology and Cas9 nucleases in combating antimicrobial resistance.
Methods
The literature review followed the PRISMA guidelines using PubMed, Embase, and Scopus databases until July 2023.
Results
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%.
Conclusions
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.
{"title":"Unravelling the advances of CRISPR-Cas9 as a precise antimicrobial therapy: A systematic review","authors":"Hannay Crystynah Almeida de Souza , Pedro Panzenhagen , Anamaria Mota Pereira dos Santos , Ana Beatriz Portes , Juliana Fidelis , Carlos Adam Conte-Junior","doi":"10.1016/j.jgar.2025.02.002","DOIUrl":"10.1016/j.jgar.2025.02.002","url":null,"abstract":"<div><div>Antimicrobial resistance 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.</div></div><div><h3>Objective</h3><div>This review explores the potential of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology and Cas9 nucleases in combating antimicrobial resistance.</div></div><div><h3>Methods</h3><div>The literature review followed the PRISMA guidelines using PubMed, Embase, and Scopus databases until July 2023.</div></div><div><h3>Results</h3><div>The <em>Enterobacterales</em> family, particularly <em>Escherichia coli</em>, was the main focus. The resistance genes targeted were mainly associated with β-lactam antibiotics, specifically <em>bla</em> genes, and colistin resistance linked to the <em>mcr-1</em> 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%.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"42 ","pages":"Pages 51-60"},"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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: 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.
Methods: 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.
Results: 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%).
Conclusions: 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.
{"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}
To describe the molecular characterisation of an Enterobacter cloacae strain resistant to cefiderocol and co-harbouring blaIMP-19 and mcr-4.3 resistance genes
Methods
The strain was isolated from the rectal swab of a 77-year-old woman during screening for the detection of patients colonised by carbapenemase-producing Enterobacterales (CPE) in Bologna (Italy). The strain was identified at species level by MALDI-TOF mass spectrometry and the presence of active-on-imipenem (IMP) carbapenemase was confirmed both by a phenotypic immunochromatographic method, and by a rapid commercial nucleic acid amplification test. The strain underwent antimicrobial susceptibility testing and its genome was fully characterised to assess (i) the multilocus sequence type, (ii) the presence of antimicrobial resistance (AMR) genes, and (iii) the presence of virulence genes coupled with mobile genetic elements.
Results
Multilocus sequence typing identified the strain as ST837. A plasmid of 60 691 bp, very similar to the MW574937 plasmid of Escherichia coli, was identified and carried the following AMR genes: aac(6′)-II, blaBEL-1, blaIMP-19, msr(E), mph(E), and sul1. This plasmid harboured several tra genes (traB, traC, traD, traG, traI, traJ, traKtraL, and traM) of the transfer operon of the E. coli conjugative F plasmid. Other AMR genes were located in the chromosome (blaCMH-3 and fosA) or in other plasmids (blaSHV-12 and mcr-4.3). The strain showed resistance to many β-lactams in vitro, including cefiderocol, whereas, despite the presence of the mcr-4.3 gene, it was susceptible to colistin.
Conclusions
Further studies are needed to better evaluate the origin of this strain and monitor the presence of Gram-negative bacilli with a similar molecular structure in our area.
{"title":"First report of an Enterobacter cloacae ST837 resistant to cefiderocol co-harbouring blaIMP-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":"10.1016/j.jgar.2025.01.023","url":null,"abstract":"<div><h3>Objective</h3><div>To describe the molecular characterisation of an <em>Enterobacter cloacae</em> strain resistant to cefiderocol and co-harbouring <em>bla</em><sub>IMP-19</sub> and <em>mcr-4.3</em> resistance genes</div></div><div><h3>Methods</h3><div>The strain was isolated from the rectal swab of a 77-year-old woman during screening for the detection of patients colonised by carbapenemase-producing Enterobacterales (CPE) in Bologna (Italy). The strain was identified at species level by MALDI-TOF mass spectrometry and the presence of active-on-imipenem (IMP) carbapenemase was confirmed both by a phenotypic immunochromatographic method, and by a rapid commercial nucleic acid amplification test. The strain underwent antimicrobial susceptibility testing and its genome was fully characterised to assess (i) the multilocus sequence type, (ii) the presence of antimicrobial resistance (AMR) genes, and (iii) the presence of virulence genes coupled with mobile genetic elements.</div></div><div><h3>Results</h3><div>Multilocus sequence typing identified the strain as ST837. A plasmid of 60 691 bp, very similar to the MW574937 plasmid of <em>Escherichia coli</em>, was identified and carried the following AMR genes: <em>aac(6′)-II</em>, bla<sub>BEL-1</sub>, <em>bla</em><sub>IMP-19</sub>, <em>msr(E), mph(E)</em>, and <em>sul1.</em> This plasmid harboured several <em>tra</em> genes (<em>traB, traC, traD, traG, traI, traJ, traKtraL</em>, and <em>traM</em>) of the transfer operon of the <em>E. coli</em> conjugative F plasmid. Other AMR genes were located in the chromosome (<em>bla</em><sub>CMH-3</sub> and <em>fosA</em>) or in other plasmids (<em>bla</em><sub>SHV-12</sub> and <em>mcr-4.3</em>). The strain showed resistance to many β-lactams in vitro, including cefiderocol, whereas, despite the presence of the <em>mcr-4.3</em> gene, it was susceptible to colistin.</div></div><div><h3>Conclusions</h3><div>Further studies are needed to better evaluate the origin of this strain and monitor the presence of Gram-negative bacilli with a similar molecular structure in our area.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"42 ","pages":"Pages 37-41"},"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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-11DOI: 10.1016/j.jgar.2025.01.022
Aimee Songo, Hervé Jacquier, Maxime Danjean, Fabrice Compain, Delphine Dorchène, Zainab Edoo, Paul-Louis Woerther, Michel Arthur, David Lebeaux
Objective: 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.
Methods: 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 (blaBRA-1 and blaBRS-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).
Results: 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.
Conclusion: N. brasiliensis HUJEG-1 resistance to penams and cephems was mainly due to the class A β-lactamase BRA-1.
{"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<sub>BRA-1</sub> and bla<sub>BRS-1</sub>) 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}
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