Pub Date : 2025-01-31DOI: 10.1016/j.jgar.2025.01.020
Carlton Cannon, Seon Woo Kim, Jung-Lim Lee, Jo Ann S Van Kessel, Bradd J Haley
Objective: 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.
Methods: 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.
Results: 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 blaPLA, 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.
Conclusions: 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.
{"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<sub>PLA</sub>, 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}
Pub Date : 2025-01-30DOI: 10.1016/j.jgar.2025.01.013
Ikuri Alvarez-Maya , Manuel Garcia-Ulloa , Armando Martinez-Guarneros , Carlos A. Vazquez-Chacon , Jaime Martinez-Urtaza
Background
Tuberculosis disease is a major global health concern. In Mexico, information regarding the genomic variants of Mycobacterium tuberculosis (MTB) prevailing in the country and the existence of specific biogeographical patterns remains extremely scarce.
Objective
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.
Methods
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.
Results
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 l-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 (ddn).
Conclusion
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.
{"title":"Nationwide phylogenomic surveillance of Mycobacterium tuberculosis in Mexico reveals pathogenic and drug resistant signatures of the prevailing L4 sublineage","authors":"Ikuri Alvarez-Maya , Manuel Garcia-Ulloa , Armando Martinez-Guarneros , Carlos A. Vazquez-Chacon , 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}
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
{"title":"Imipenem/Cilastatin encapsulation in UIO-66-NH<sub>2</sub> 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-NH<sub>2</sub>, 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-NH<sub>2</sub>-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-NH<sub>2</sub>-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-NH<sub>2</sub>-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-NH<sub>2</sub>-Imp/Cil formulation compared to free Imp/Cil, demonstrating enhanced antibacterial activity. Furthermore, the anti-biofilm and anti-virulence activity of UIO-66-NH<sub>2</sub>-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-NH<sub>2</sub>-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-NH<sub>2</sub>-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}
Pub Date : 2025-01-30DOI: 10.1016/j.jgar.2025.01.014
Estera Jachowicz-Matczak, Tomasz Wołkowicz, Anna Kujawska, Anna Pałka, Mateusz Gajda, Barbara Żółtowska, Katarzyna Zacharczuk, Katarzyna Piekarska, Jakub Kasprzyk, Natalia Wieczorek, Rafał Gierczyński, Jadwiga Wójkowska-Mach
Background: Acinetobacter baumannii (Ab) causes severe infections among intensive care units (ICU) and mechanically ventilated patients. According to the European Centre for Disease Prevention and Control data for 2018 the prevalence of Ab in Polish ICUs was higher than in other European countries, while almost 40% of Ab were resistant to carbapenems (CR-Ab) in 2021. Our goal was to investigate the epidemiology and molecular characteristics of CR-Ab strains collected from the University Hospital in Krakow, Poland, by whole-genome sequencing (WGS) and phenotypic tests.
Methods: Epidemiological and drug-resistance data from a total of 667 hospital-acquired (HAI) CR-Ab infections collected in 2019 (442) and 2021 (235) were examined. Bacterial identification, antimicrobial susceptibility and detection of carbapenemases were performed. A selected subset of 125 CR-Ab isolated in 2021 was investigated by WGS.
Results: Among 125 CR-Ab isolates examined by WGS, the vast majority 104 (82%), belonged to the most prevalent ST2, and whereas 20 (16%) belonged to the rarely reported ST600. The most common genes conferring resistance to carbapenems were blaOXA-66 (96.8%), and blaOXA-72 (71.2%), whereas blaOXA-23 and blaNDM-1 genes were specific to ST600 isolates. The blaNDM-1 gene was chromosomally located in IS30 of Tn125.
Conclusions: Our study reveals the presence of CR-Ab of the sporadically reported ST600 harbouring the blaNDM-1 gene, reported for the first time in Poland. Routine genomic surveillance should be implemented to monitor and reduce the transmission of circulating resistant Ab clones.
{"title":"Epidemiological and genomic characterization of carbapenem-resistant Acinetobacter baumannii ST600 harbouring the bla<sub>NDM-1</sub> gene, first report in Poland.","authors":"Estera Jachowicz-Matczak, Tomasz Wołkowicz, Anna Kujawska, Anna Pałka, Mateusz Gajda, Barbara Żółtowska, Katarzyna Zacharczuk, Katarzyna Piekarska, Jakub Kasprzyk, Natalia Wieczorek, Rafał Gierczyński, Jadwiga Wójkowska-Mach","doi":"10.1016/j.jgar.2025.01.014","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.014","url":null,"abstract":"<p><strong>Background: </strong>Acinetobacter baumannii (Ab) causes severe infections among intensive care units (ICU) and mechanically ventilated patients. According to the European Centre for Disease Prevention and Control data for 2018 the prevalence of Ab in Polish ICUs was higher than in other European countries, while almost 40% of Ab were resistant to carbapenems (CR-Ab) in 2021. Our goal was to investigate the epidemiology and molecular characteristics of CR-Ab strains collected from the University Hospital in Krakow, Poland, by whole-genome sequencing (WGS) and phenotypic tests.</p><p><strong>Methods: </strong>Epidemiological and drug-resistance data from a total of 667 hospital-acquired (HAI) CR-Ab infections collected in 2019 (442) and 2021 (235) were examined. Bacterial identification, antimicrobial susceptibility and detection of carbapenemases were performed. A selected subset of 125 CR-Ab isolated in 2021 was investigated by WGS.</p><p><strong>Results: </strong>Among 125 CR-Ab isolates examined by WGS, the vast majority 104 (82%), belonged to the most prevalent ST2, and whereas 20 (16%) belonged to the rarely reported ST600. The most common genes conferring resistance to carbapenems were bla<sub>OXA-66</sub> (96.8%), and bla<sub>OXA-72</sub> (71.2%), whereas bla<sub>OXA-23</sub> and bla<sub>NDM-1</sub> genes were specific to ST600 isolates. The bla<sub>NDM-1</sub> gene was chromosomally located in IS30 of Tn125.</p><p><strong>Conclusions: </strong>Our study reveals the presence of CR-Ab of the sporadically reported ST600 harbouring the bla<sub>NDM-1</sub> gene, reported for the first time in Poland. Routine genomic surveillance should be implemented to monitor and reduce the transmission of circulating resistant Ab clones.</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":"143074348","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 : 2025-01-29DOI: 10.1016/j.jgar.2025.01.006
Cindy Kundlacz, Yasmine Eddoubaji, Vincent Perreten, Andrea Endimiani, Edgar I Campos-Madueno
Background: .Enterococcus spp. are typically found in multiple settings and are sometimes responsible for difficult-to-treat infections. In this context, very little is known about E. devriesei, a rare species first isolated from a river lamprey. Importantly, no complete genome of E. devriesei currently exists in public repositories.
Methods: . An E. devriesei strain (Ed-CK-24) was isolated from homogenized Zophobas morio larvae. Initial species identification (ID) was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility testing (AST) was performed by broth microdilution. Whole-genome sequencing (WGS) was done using both Illumina NovaSeq 6000 and Nanopore MinION to generate a complete genome assembly. WGS data were used to confirm species ID, antimicrobial resistance genes (ARGs) and plasmid replicon sequences screening. A database search for other E. devriesei genomes in NCBI was performed and used for 16S rRNA and core-genome phylogeny analyses.
Results: . WGS and bioinformatic analyses were performed, resulting in a complete genome assembly and allowing accurate taxonomic classification of Ed-CK-24 strain as E. devriesei. Alignment of 16S rRNA sequences of representative Enterococcus spp. further supported the ID of Ed-CK-24. A core-genome phylogenetic analysis revealed no clonal relationships between Ed-CK-24 and other E. devriesei derived from multiple sources. The Ed-CK-24 strain was resistant to clindamycin and quinupristin/dalfopristin. ARG screening identified the lsa(A) gene, carried on a 633,497-bp circular megaplasmid.
Conclusions: . WGS of Ed-CK-24 allowed high-resolution genomic comparison and epidemiologic analysis of E. devriesei. Its isolation from Z. morio larvae, commonly used in pet food, warns for further surveillance as the human pathogenic potential of this species remains unknown.
{"title":"Complete genome sequence of an Enterococcus devriesei strain isolated from Zophobas morio larvae: Complete genome of Enterococcus devriesei Ed-CK-24.","authors":"Cindy Kundlacz, Yasmine Eddoubaji, Vincent Perreten, Andrea Endimiani, Edgar I Campos-Madueno","doi":"10.1016/j.jgar.2025.01.006","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.006","url":null,"abstract":"<p><strong>Background: </strong>.Enterococcus spp. are typically found in multiple settings and are sometimes responsible for difficult-to-treat infections. In this context, very little is known about E. devriesei, a rare species first isolated from a river lamprey. Importantly, no complete genome of E. devriesei currently exists in public repositories.</p><p><strong>Methods: </strong>. An E. devriesei strain (Ed-CK-24) was isolated from homogenized Zophobas morio larvae. Initial species identification (ID) was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility testing (AST) was performed by broth microdilution. Whole-genome sequencing (WGS) was done using both Illumina NovaSeq 6000 and Nanopore MinION to generate a complete genome assembly. WGS data were used to confirm species ID, antimicrobial resistance genes (ARGs) and plasmid replicon sequences screening. A database search for other E. devriesei genomes in NCBI was performed and used for 16S rRNA and core-genome phylogeny analyses.</p><p><strong>Results: </strong>. WGS and bioinformatic analyses were performed, resulting in a complete genome assembly and allowing accurate taxonomic classification of Ed-CK-24 strain as E. devriesei. Alignment of 16S rRNA sequences of representative Enterococcus spp. further supported the ID of Ed-CK-24. A core-genome phylogenetic analysis revealed no clonal relationships between Ed-CK-24 and other E. devriesei derived from multiple sources. The Ed-CK-24 strain was resistant to clindamycin and quinupristin/dalfopristin. ARG screening identified the lsa(A) gene, carried on a 633,497-bp circular megaplasmid.</p><p><strong>Conclusions: </strong>. WGS of Ed-CK-24 allowed high-resolution genomic comparison and epidemiologic analysis of E. devriesei. Its isolation from Z. morio larvae, commonly used in pet food, warns for further surveillance as the human pathogenic potential of this species remains unknown.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074207","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 : 2025-01-28DOI: 10.1016/j.jgar.2025.01.018
A De Vito, A Bezenchek, R Scutari, L Colagrossi, G Valenti, M C Bellocchi, L Pipitò, S Ferrara, S Malandrin, M Tallarita, A Cozzi-Lepri, F Ceccherini Silberstein, S Lo Caputo, S Rusconi
Purpose: We aimed to assess the utilization of Genotype Resistance Testing (GRT) by Infectious Diseases Units across Italy.
Methods: A cross-sectional study was conducted involving a questionnaire distributed to the Infectious Diseases Unit in Italy. A web-based survey using Google Forms software was utilized and spread via email or cellphone.
Results: Responses were obtained from 101 Infectious Diseases Units. Among these centers, only seven (6.9%) reported not performing GRT at any time. Of the 94 centers performing GRT, 52 (55.3%) sent blood samples to external laboratories. Notably, only 6/35 (17.1%) small centers had internal laboratories, compared to 14/35 (40.0%) medium centers and 22/24 (91.7%) large centers (p<0.001). Most centers requested GRT for treatment-naïve individuals and all cases of virological failure. Only 24 (25.5%) requested GRT of HIVDNA before treatment changes. Regarding virological failure, most centers (38, 40.4%) requested GRT when HIV-RNA levels exceeded 200 copies/mL, while 26 (27.7%) requested it at levels exceeding 50 copies/mL. Additionally, 18 (19.1%) and 12 (12.8%) centers requested GRT at thresholds of 500 copies/mL and 1000 copies/mL, respectively. Regarding the specific GRT test used, 34 (36.2%) were unsure, while 16 (17.0%) reported using both Next-Generation Sequencing (NGS) and Sanger methods. Furthermore, 30 (31.9%) and 14 (14.9%) centers exclusively used NGS and Sanger, respectively. Most centers reported receiving GRT results within one month (n=72, 76.6%), while 22 (23.4%) centers obtained results within two weeks. However, 22 (23.4%) centers typically experienced more than one-month delays. Finally, most participants (86, 91.5%) regarded GRT as a crucial routine test for the treatment of naïve PLWH.
Conclusion: This study demonstrates that most Infectious Diseases Units in Italy continue to consider GRT an essential test for newly diagnosed PLWH in clinical practice. However, the utilization of GRT on HIV-DNA remains limited. Further efforts are required to decrease turnaround time in centers experiencing prolonged delays in obtaining results.
{"title":"Assessing the Utilization of HIV Genotype Resistance Testing: Insight from Italian Infectious Diseases Units.","authors":"A De Vito, A Bezenchek, R Scutari, L Colagrossi, G Valenti, M C Bellocchi, L Pipitò, S Ferrara, S Malandrin, M Tallarita, A Cozzi-Lepri, F Ceccherini Silberstein, S Lo Caputo, S Rusconi","doi":"10.1016/j.jgar.2025.01.018","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.018","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to assess the utilization of Genotype Resistance Testing (GRT) by Infectious Diseases Units across Italy.</p><p><strong>Methods: </strong>A cross-sectional study was conducted involving a questionnaire distributed to the Infectious Diseases Unit in Italy. A web-based survey using Google Forms software was utilized and spread via email or cellphone.</p><p><strong>Results: </strong>Responses were obtained from 101 Infectious Diseases Units. Among these centers, only seven (6.9%) reported not performing GRT at any time. Of the 94 centers performing GRT, 52 (55.3%) sent blood samples to external laboratories. Notably, only 6/35 (17.1%) small centers had internal laboratories, compared to 14/35 (40.0%) medium centers and 22/24 (91.7%) large centers (p<0.001). Most centers requested GRT for treatment-naïve individuals and all cases of virological failure. Only 24 (25.5%) requested GRT of HIVDNA before treatment changes. Regarding virological failure, most centers (38, 40.4%) requested GRT when HIV-RNA levels exceeded 200 copies/mL, while 26 (27.7%) requested it at levels exceeding 50 copies/mL. Additionally, 18 (19.1%) and 12 (12.8%) centers requested GRT at thresholds of 500 copies/mL and 1000 copies/mL, respectively. Regarding the specific GRT test used, 34 (36.2%) were unsure, while 16 (17.0%) reported using both Next-Generation Sequencing (NGS) and Sanger methods. Furthermore, 30 (31.9%) and 14 (14.9%) centers exclusively used NGS and Sanger, respectively. Most centers reported receiving GRT results within one month (n=72, 76.6%), while 22 (23.4%) centers obtained results within two weeks. However, 22 (23.4%) centers typically experienced more than one-month delays. Finally, most participants (86, 91.5%) regarded GRT as a crucial routine test for the treatment of naïve PLWH.</p><p><strong>Conclusion: </strong>This study demonstrates that most Infectious Diseases Units in Italy continue to consider GRT an essential test for newly diagnosed PLWH in clinical practice. However, the utilization of GRT on HIV-DNA remains limited. Further efforts are required to decrease turnaround time in centers experiencing prolonged delays in obtaining results.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065856","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 : 2025-01-28DOI: 10.1016/j.jgar.2025.01.015
Minna Rud Andreasen , Filip Jansåker , Jesper Iversen , Opeyemi U. Lawal , Maria Miragaia , Luisa Gonçalves , Paulo Paixão , Elsa Gonçalves , Cristina Toscano , Maria D. Luzon , Małgorzata Urbaś , Lotte Jelsbak , Henrik Westh , Jenny Dahl Knudsen
Objectives
Staphylococcus saprophyticus (S. saprophyticus) is the second most common bacteria causing uncomplicated urinary tract infections (UTIs). It is considered non-susceptible to mecillinam, with no defined breakpoint and only few available minimal inhibitory concentration (MIC) observations. However, this consideration does not correlate with clinical outcome. With this study, we aimed to provide a comprehensive MIC distribution analysis of mecillinam for S. saprophyticus, which could be useful for determining potential breakpoints.
Methods
We studied 112 isolates of S. saprophyticus from human urine samples from 4 European countries. The broth microdilution and MIC test strip methods were used to determine mecillinam MIC.
Results
Broth microdilution MICs ranged from 4 to ≥ 256 mg/L, with a binary clustering at 32 to 64 and ≥ 256 mg/L. The MICs were duplicated for each isolate with similar results. The MIC distribution from the test strip method aligned well with the results from the broth microdilution method. Disc diffusion test yielded an 8 mm inhibitory zone in three isolates with MIC of 32 mg/L.
Pub Date : 2025-01-27DOI: 10.1016/j.jgar.2025.01.016
Ana C. Almeida-Santos , Carla Novais , Luísa Peixe , Ana R. Freitas
Vancomycin-resistant Enterococcus faecium (VREfm) has become a critical opportunistic pathogen, urgently requiring new antimicrobial strategies due to its rising prevalence and significant impact on patient safety and healthcare costs. VREfm continues to evolve through mutations and the acquisition of new genes via horizontal gene transfer, contributing to resistance against several last-resort antibiotics. Although primarily hospital-associated, VREfm are also detected in the community, food chain, livestock, and environmental sources like wastewater, indicating diverse transmission pathways and the need for a One Health approach. Advances in genomics have shed light on VREfm's persistence in hospital settings, particularly its adaptation to the gastrointestinal tract of hospitalized patients, recent clonal shifts, and the dominance of specific clonal lineages. Despite extensive research, significant gaps remain in understanding the molecular mechanisms behind VREfm's unique adaptation to clinical environments. In this review, we aim to present an overview of VREfm current prevalence, mechanisms of resistance, and unveil the adaptive traits that have facilitated VREfm's rise and global success. A particular focus is given to key plasmids, namely linear plasmids, virulence factors, and bacteriocins as potential drivers in the global emergence of the ST78 clonal lineage. We also address diagnostic challenges and the limited treatment options available for VREfm, as well as emerging antibiotic alternatives aimed at restoring gut microbiota balance and curbing VREfm proliferation. A multifaceted approach combining research, clinical practices, and public health policies is crucial to mitigate the impact of this superbug and preserve antimicrobial effectiveness for future generations.
{"title":"Vancomycin-resistant Enterococcus faecium: A current perspective on resilience, adaptation, and the urgent need for novel strategies","authors":"Ana C. Almeida-Santos , Carla Novais , Luísa Peixe , Ana R. Freitas","doi":"10.1016/j.jgar.2025.01.016","DOIUrl":"10.1016/j.jgar.2025.01.016","url":null,"abstract":"<div><div>Vancomycin-resistant <em>Enterococcus faecium</em> (VREfm) has become a critical opportunistic pathogen, urgently requiring new antimicrobial strategies due to its rising prevalence and significant impact on patient safety and healthcare costs. VREfm continues to evolve through mutations and the acquisition of new genes via horizontal gene transfer, contributing to resistance against several last-resort antibiotics. Although primarily hospital-associated, VREfm are also detected in the community, food chain, livestock, and environmental sources like wastewater, indicating diverse transmission pathways and the need for a One Health approach. Advances in genomics have shed light on VREfm's persistence in hospital settings, particularly its adaptation to the gastrointestinal tract of hospitalized patients, recent clonal shifts, and the dominance of specific clonal lineages. Despite extensive research, significant gaps remain in understanding the molecular mechanisms behind VREfm's unique adaptation to clinical environments. In this review, we aim to present an overview of VREfm current prevalence, mechanisms of resistance, and unveil the adaptive traits that have facilitated VREfm's rise and global success. A particular focus is given to key plasmids, namely linear plasmids, virulence factors, and bacteriocins as potential drivers in the global emergence of the ST78 clonal lineage. We also address diagnostic challenges and the limited treatment options available for VREfm, as well as emerging antibiotic alternatives aimed at restoring gut microbiota balance and curbing VREfm proliferation. A multifaceted approach combining research, clinical practices, and public health policies is crucial to mitigate the impact of this superbug and preserve antimicrobial effectiveness for future generations.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"41 ","pages":"Pages 233-252"},"PeriodicalIF":3.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065871","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 : 2025-01-27DOI: 10.1016/j.jgar.2025.01.008
Arina Šablinskaja , Hiie Soeorg , Merit Pauskar , Ene-Ly Jõgeda , Heli Rajasaar , Pilleriin Soodla , Eveli Kallas , Kati Hensen , Jekaterina Tabri , Kristi Rüütel , Taavi Päll , Irja Lutsar , Kristi Huik , Radko Avi
Objectives
We investigated the prevalence of drug resistance mutations (DRMs) in individuals newly diagnosed with HIV-1 in Estonia in 2020 and 2022, and in Ukrainian war refugees living with HIV who arrived in Estonia in 2022.
Methods
HIV-1 genomic RNA was sequenced in protease-reverse transcriptase and integrase (IN) regions. DRMs were determined separately by Stanford University CPR Tool and HIVdb Program. REGA HIV-1 Subtyping Tool and phylogenetic analysis were used for subtyping.
Results
Both regions were successfully sequenced in 79 and 53 individuals in 2020 and 2022 populations, respectively. The DRM rates were 11.4% [95% CI, 5.3%–20.5%] in 2020 and 13.2% [95% CI 5.5%–25.3%] in 2022. There was a low percentage of resistance to IN strand transfer inhibitors: 3.8% [95% CI, 0.8–10.7] in 2020 and 1.9% [95% CI, 0.05–10.1] in 2022. Most Ukrainian war refugees had undetectable VL (57/88, 65%), were women (63%) and majority were infected with subtype A6 viruses. The overall DRM rate for Ukrainian population was 11.5%.
Conclusions
Identifying HIV DRMs using HIVdb Program combined with CPR tools gives comprehensive overview of transmitted drug resistance. Resistance testing might be necessary before initiating antiretroviral therapy if the first-line treatment does not include PI or second-generation IN strand transfer inhibitors.
{"title":"Transmitted HIV-1 drug resistance in Estonian residents and Ukrainian refugees in 2020 and 2022","authors":"Arina Šablinskaja , Hiie Soeorg , Merit Pauskar , Ene-Ly Jõgeda , Heli Rajasaar , Pilleriin Soodla , Eveli Kallas , Kati Hensen , Jekaterina Tabri , Kristi Rüütel , Taavi Päll , Irja Lutsar , Kristi Huik , Radko Avi","doi":"10.1016/j.jgar.2025.01.008","DOIUrl":"10.1016/j.jgar.2025.01.008","url":null,"abstract":"<div><h3>Objectives</h3><div>We investigated the prevalence of drug resistance mutations (DRMs) in individuals newly diagnosed with HIV-1 in Estonia in 2020 and 2022, and in Ukrainian war refugees living with HIV who arrived in Estonia in 2022.</div></div><div><h3>Methods</h3><div>HIV-1 genomic RNA was sequenced in protease-reverse transcriptase and integrase (IN) regions. DRMs were determined separately by Stanford University CPR Tool and HIVdb Program. REGA HIV-1 Subtyping Tool and phylogenetic analysis were used for subtyping.</div></div><div><h3>Results</h3><div>Both regions were successfully sequenced in 79 and 53 individuals in 2020 and 2022 populations, respectively. The DRM rates were 11.4% [95% CI, 5.3%–20.5%] in 2020 and 13.2% [95% CI 5.5%–25.3%] in 2022. There was a low percentage of resistance to IN strand transfer inhibitors: 3.8% [95% CI, 0.8–10.7] in 2020 and 1.9% [95% CI, 0.05–10.1] in 2022. Most Ukrainian war refugees had undetectable VL (57/88, 65%), were women (63%) and majority were infected with subtype A6 viruses. The overall DRM rate for Ukrainian population was 11.5%.</div></div><div><h3>Conclusions</h3><div>Identifying HIV DRMs using HIVdb Program combined with CPR tools gives comprehensive overview of transmitted drug resistance. Resistance testing might be necessary before initiating antiretroviral therapy if the first-line treatment does not include PI or second-generation IN strand transfer inhibitors.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"41 ","pages":"Pages 258-265"},"PeriodicalIF":3.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047070","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 : 2025-01-24DOI: 10.1016/j.jgar.2025.01.007
Alex Soriano, David L Paterson, Florian Thalhammer, Stefan Kluge, Pierluigi Viale, Alexandre H Watanabe, Mike Allen, Brune Akrich, Stephanie Wirbel, Engels N Obi, Emre Yücel, Sundeep Kaul
Objectives: Antibacterial-resistant gram-negative hospital-acquired infections result in significant morbidity and mortality. In clinical trials, ceftolozane/tazobactam (C/T) has been effective against these infections; however, real-world findings are limited.
Methods: SPECTRA was a global, retrospective, observational inpatient study of adults treated with C/T for ≥48 hours, conducted between 2016 and 2020. The primary objective was to describe real-world utilisation of C/T: socio-demographic, clinical characteristics, prescribing patterns, clinical outcomes, and healthcare resource utilisation in hospitalized patients treated with C/T.
Results: In total, 617 patients from 7 countries met inclusion criteria. Most (82.7%) had ≥1 comorbidity. The most common medical conditions where C/T was used were pneumonia (29.5%), sepsis (20.4%), complicated intra-abdominal infection (15.1%), and complicated urinary tract infection (14.4%). The most common pathogens were Pseudomonas aeruginosa (87.4%) and Escherichia coli (8.2%). Median C/T treatment duration was 11 days. Clinical success occurred in 67.3% of patients (including those with 'unknown' status in the denominator). In a separate analysis that excluded those with 'unknown' status, clinical success ranged from 94.1% in patients with bacteraemia to 58.9% with sepsis. Overall, 18.8% of patients had documented microbiologic response. All-cause in-hospital mortality was 21.2%; infection-related mortality was 7.6%. Median hospital length of stay was 42 days (30 days for those who received early C/T therapy [before pathogen identification] vs. 48 days for definitive therapy [after identification]).
Conclusions: These data elucidate real-world utilisation and prescribing patterns of C/T in a diverse patient population with complex medical conditions and various profiles of pathogen resistance between 2016 and 2020.
{"title":"Unveiling results and insights from multinational, multicenter Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam Real-world Analysis (SPECTRA).","authors":"Alex Soriano, David L Paterson, Florian Thalhammer, Stefan Kluge, Pierluigi Viale, Alexandre H Watanabe, Mike Allen, Brune Akrich, Stephanie Wirbel, Engels N Obi, Emre Yücel, Sundeep Kaul","doi":"10.1016/j.jgar.2025.01.007","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.01.007","url":null,"abstract":"<p><strong>Objectives: </strong>Antibacterial-resistant gram-negative hospital-acquired infections result in significant morbidity and mortality. In clinical trials, ceftolozane/tazobactam (C/T) has been effective against these infections; however, real-world findings are limited.</p><p><strong>Methods: </strong>SPECTRA was a global, retrospective, observational inpatient study of adults treated with C/T for ≥48 hours, conducted between 2016 and 2020. The primary objective was to describe real-world utilisation of C/T: socio-demographic, clinical characteristics, prescribing patterns, clinical outcomes, and healthcare resource utilisation in hospitalized patients treated with C/T.</p><p><strong>Results: </strong>In total, 617 patients from 7 countries met inclusion criteria. Most (82.7%) had ≥1 comorbidity. The most common medical conditions where C/T was used were pneumonia (29.5%), sepsis (20.4%), complicated intra-abdominal infection (15.1%), and complicated urinary tract infection (14.4%). The most common pathogens were Pseudomonas aeruginosa (87.4%) and Escherichia coli (8.2%). Median C/T treatment duration was 11 days. Clinical success occurred in 67.3% of patients (including those with 'unknown' status in the denominator). In a separate analysis that excluded those with 'unknown' status, clinical success ranged from 94.1% in patients with bacteraemia to 58.9% with sepsis. Overall, 18.8% of patients had documented microbiologic response. All-cause in-hospital mortality was 21.2%; infection-related mortality was 7.6%. Median hospital length of stay was 42 days (30 days for those who received early C/T therapy [before pathogen identification] vs. 48 days for definitive therapy [after identification]).</p><p><strong>Conclusions: </strong>These data elucidate real-world utilisation and prescribing patterns of C/T in a diverse patient population with complex medical conditions and various profiles of pathogen resistance between 2016 and 2020.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047071","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}