107 results on '"enterobacterales"'
Search Results
2. Integral genomic description of blaNDM-5-harbouring plasmids recovered from Enterobacterales in Argentina.
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González-Espinosa, Francisco, Di Pilato, Vincenzo, Calabrese, Luca, Costa, Elisa, Costa, Agustina, Gutkind, Gabriel, Cejas, Daniela, and Radice, Marcela
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- 2024
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3. Evaluation of the activity of cefepime/enmetazobactam against Enterobacterales bacteria collected in Europe from 2019 to 2021, including third-generation cephalosporin-resistant isolates
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Ian Morrissey, Stephen Hawser, Nimmi Kothari, Nathalie Dunkel, Juan Quevedo, Adam Belley, Anne Santerre Henriksen, and Marie Attwood
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Enterobacterales ,Enmetazobactam ,ESBL ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: This study was performed to investigate the activity of the novel ß-lactam/ß-lactamase inhibitor combination cefepime/enmetazobactam, against recently circulating Enterobacterales isolates from Europe from 2019 to 2021. Methods: A total of 2627 isolates were collected, and antimicrobial susceptibility was determined according to the European Committee on Antimicrobial Susceptibility Testing guidelines. Isolates with phenotypic resistance to ceftriaxone and ceftazidime (but susceptible to meropenem) and isolates nonsusceptible to meropenem were screened for the presence of ß-lactamases. Results: Overall, susceptibility to third-generation cephalosporins was 77%, and 97.3% were susceptible to meropenem. Cefepime/enmetazobactam susceptibility was 97.9% (72% of these isolates were Klebsiella pneumoniae from Italy), compared with 80.0% susceptibility to piperacillin/tazobactam and 99.4% to ceftazidime/avibactam. A total of 320 isolates (12.2%) were resistant to third-generation cephalosporins but susceptible to meropenem, and virtually all (96.3%) carried an extended-spectrum ß-lactamase with or without an AmpC and these were all susceptible to cefepime/enmetazobactam. Most meropenem-nonsusceptible isolates carried a KPC (68%), which were not inhibited by cefepime/enmetazobactam but were inhibited by ceftazidime/avibactam. Additionally, most meropenem-nonsusceptible isolates carrying OXA-48 (9/12 isolates) were susceptible to cefepime/enmetazobactam. Conclusions: Cefepime/enmetazobactam was highly active against Enterobacterales isolates, especially those resistant to third-generation cephalosporins. These data suggest that cefepime/enmetazobactam could be used as a carbapenem-sparing agent to replace piperacillin/tazobactam. more...
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- 2024
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4. Global trends in carbapenem- and difficult-to-treat-resistance among World Health Organization priority bacterial pathogens: ATLAS surveillance program 2018–2022
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Mark G. Wise, James A. Karlowsky, Naglaa Mohamed, Elizabeth D. Hermsen, Shweta Kamat, Andy Townsend, Adrian Brink, Alex Soriano, David L. Paterson, Luke S.P. Moore, and Daniel F. Sahm
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Enterobacterales ,Pseudomonas aeruginosa ,Acinetobacter baumannii-calcoaceticus complex ,Carbapenem resistance ,Difficult-to-treat resistance ,Surveillance ,Microbiology ,QR1-502 - Abstract
Objectives: To report trends in carbapenem resistance and difficult-to-treat resistance (DTR) among clinical isolates of Gram-negative priority pathogens collected by the ATLAS global surveillance program from 2018 to 2022. Methods: Reference broth microdilution testing was performed in a central laboratory for 79,214 Enterobacterales, 30,504 Pseudomonas aeruginosa, and 13,500 Acinetobacter baumannii-calcoaceticus complex isolates collected by a constant set of 157 medical centres in 49 countries in Asia Pacific (APAC), Europe (EUR), Latin America (LATAM), Middle East-Africa (MEA), and North America (NA) regions. MICs were interpreted by 2023 CLSI M100 breakpoints. β-lactamase genes were identified for meropenem-nonsusceptible (MIC ≥2 mg/L) Enterobacterales isolates. Results: Carbapenem-resistant Enterobacterales (CRE) detection increased (P < 0.05) in APAC, EUR, LATAM, and MEA regions and decreased in NA, while annual DTR percentages increased in all five regions. Carbapenem-resistant P. aeruginosa (CRPA; decreased in MEA region) and carbapenem-resistant A. baumannii-calcoaceticus complex (CRAB; decreased in MEA region and increased in EUR) remained relatively stable over time in all regions, although notably, annual percentages of CRAB and DTR A. baumannii-calcoaceticus complex isolates were consistently >25 percentage points lower in NA than in other regions. For all regions except NA, the majority of changes in CRE percentages could be attributed to hospital-acquired infections. Among meropenem-nonsusceptible Enterobacterales, KPC was the most frequent carbapenemase in NA and EUR each year. NDM was the most prevalent carbapenemase detected in 2022 in other global regions. Conclusion: CRE, CRPA, CRAB, and DTR rates vary among global regions over time highlighting the need for continuing surveillance to inform treatment strategies and antimicrobial stewardship. more...
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- 2024
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5. Hybrid genome assembly of colistin-resistant mcr-1.5-producing Escherichia coli ST354 reveals phylogenomic pattern associated with urinary tract infections in Brazil
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Bruna Fuga, Fábio P. Sellera, Fernanda Esposito, Quézia Moura, Marcelo Pillonetto, and Nilton Lincopan
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Enterobacterales ,Plasmid-mediated colistin resistance ,Plasmidome ,Resistome ,Phylogenomics ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Background: The rapid and global spread of Escherichia coli carrying mcr-type genes at the human-animal-environmental interface has become a serious global public health problem. Objective: To perform a genomic investigation of a colistin-resistant E. coli strain (14005RM) causing urinary tract infection, using a hybrid de novo assembly of Illumina/Nanopore sequence data, presenting phylogenomic insights into the relationship with mcr-1-positive strains circulating at the human-animal-environmental interface, in Brazil. Methods: Genomic DNA was sequenced using both the Illumina NexSeq and Nanopore MinION platforms. De novo hybrid assembly was performed by Unicycler. Genomic data were assessed by in silico prediction and bioinformatic tools. Results: The genome assembly size was 5 333 039 bp. The mcr-1.5-positive E. coli strain 14005RM belongs to the sequence type ST354 and presented a broad resistome (antibiotics, heavy metals, disinfectants, and glyphosate) and virulome. The mcr-1.5 gene was carried by an IncI2 plasmid (p14005RM, sizing 65,458 kb). Full genome SNP-based phylogenetic analysis reveals that mcr-1.5-producing E. coli strain 14005RM is highly related (> 98% identity) to colistin-resistant mcr-1.1-positive ST354 lineages associated with urinary tract infections in Brazil since 2015. Conclusion: Mobile colistin resistance within the Brazilian One Health microbiosphere is mediated by mcr gene variants propagated by IncX4, IncHI2, and IncI2 plasmids, circulating among global clones of E. coli. more...
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- 2024
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6. Genomic scan of a healthcare-associated NDM-1-producing Citrobacter freundii ST18 isolated from a green sea turtle impacted by plastic pollution
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Valentina Aravena-Ramírez, Danny Fuentes-Castillo, Sibelle T. Vilaça, Daphne W. Goldberg, Fernanda Esposito, Taiana T. Silva-Pereira, Herrison Fontana, Fábio P. Sellera, and Nilton Lincopan
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WHO critical-priority bacteria ,Enterobacterales ,Carbapenemase ,Sea turtles ,One Health ,Genomic surveillance ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Background: Carbapenemase-producing Citrobacter freundii has been reported as a leading cause of healthcare-associated infections. Particularly, C. freundii belonging to the sequence type (ST) 18 is considered to be an emerging nosocomial clone. Objectives: To report the genomic background and phylogenomic analysis of a multidrug-resistant NDM-1-producing C. freundii ST18 (strain CF135931) isolated from an endangered green sea turtle affected by plastic pollution in Brazil. Methods: Genomic DNA was extracted and sequenced using the Illumina NextSeq platform. De novo assembly was performed by CLC Workbench, and in silico analysis accomplished by bioinformatics tools. For phylogenomic analysis, publicly available C. freundii (txid:546) genome assemblies were retrieved from the NCBI database. Results: The genome size was calculated at 5 290 351 bp, comprising 5263 total genes, 4 rRNAs, 77 tRNAs, 11ncRNAs, and 176 pseudogenes. The strain belonged to C. freundii ST18, whereas resistome analysis predicted genes encoding resistance to β-lactams (blaNDM-1, blaOXA-1, blaCMY-117, and blaTEM-1C), aminoglycosides (aph(3′')-Ib, aadA16, aph(3′)-VI, aac(6′)-Ib-cr, and aph(6)-Id), quinolones (aac(6′)-Ib-cr), macrolides (mph(A) and erm(B)), sulphonamides (sul1 and sul2), tetracyclines (tetA and tetD), and trimethoprim (dfrA27). The phylogenomic analysis revealed that CF135931 strain is closely related to international human-associated ST18 clones producing NDM-1. Conclusion: Genomic surveillance efforts are necessary for robust monitoring of the emergence of drug-resistant strains and WHO critical priority pathogens within a One Health framework. In this regard, this draft genome and associated data can improve understanding of dissemination dynamics of nosocomial clones of carbapenemase-producing C. freundii beyond hospital walls. In fact, the emergence of NDM-1-producing C. freundii of global ST18 in wildlife deserves considerable attention. more...
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- 2024
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7. In vitro activity of aztreonam-avibactam and comparators against Metallo-β-Lactamase-producing Enterobacterales from ATLAS Global Surveillance Program, 2016–2020
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Gian Maria Rossolini, Francis F. Arhin, and Michal Kantecki
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Antimicrobial activity ,Aztreonam-avibactam ,Enterobacterales ,ATLAS ,MBL-positive ,Microbiology ,QR1-502 - Abstract
Objectives: Metallo-β-lactamase (MBL)-producing Enterobacterales are a major challenge worldwide due to limited treatment options. Aztreonam-avibactam (ATM-AVI), which is under clinical development, has shown activity against MBL-positive isolates. This study evaluated the prevalence of MBL producers and the nature of enzymes among a global collection of clinical isolates of Enterobacterales from the Antimicrobial Testing Leadership and Surveillance program (ATLAS) surveillance program (2016–2020), and the antimicrobial activity of ATM-AVI and comparators against this collection. Methods: Non-duplicate clinical isolates of Enterobacterales (N = 106 686) collected across 63 countries were analysed. Antimicrobial susceptibility was performed using broth microdilution. Minimum inhibitory concentrations (MICs) were interpreted using Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing breakpoints. Provisional pharmacokinetic/pharmacodynamic breakpoint of ≤8 mg/L was considered for ATM-AVI. β-lactamase genes were characterized by polymerase chain reaction and sequencing. The Cochran Armitage Trend test was used to determine significant trends in percentage of isolates over time. Results: Overall, MBL-positive isolates were 1.6% of total Enterobacterales isolates globally, with a significant increasing trend observed over time, globally and across regions (P < 0.05). New Delhi MBL (NDM) was the most common MBL (83.3%). ATM-AVI demonstrated potent activity against MBL-positive isolates (MIC ≤8 mg/L: 99.4% isolates inhibited; MIC90, 1 mg/L). Consistent activity was also noted across different regions. Potent activity was demonstrated against different NDM variants and MBL-positive isolates co-carrying other carbapenemases (98.1% and 99.7% isolates inhibited at ≤8 mg/L, respectively). About 0.6% MBL-positive isolates (10/1707) had MICs >8 mg/L for ATM-AVI. Conclusion: ATM-AVI demonstrated potent activity against MBL-positive isolates, including NDM variants and MBL-positive isolates co-carrying other carbapenemases, and may represent a good option for treating infections caused by MBL-positive Enterobacterales. more...
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- 2024
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8. Genomic data of global clones of CTX-M-65-producing Escherichia coli ST10 from South American llamas inhabiting the Andean Highlands of Peru
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Adriana R. Cardenas-Arias, Elder Sano, Brenda Cardoso, Bruna Fuga, Fábio P. Sellera, Fernanda Esposito, Valentina Aravena-Ramírez, Dennis Carhuaricra Huaman, Carla Duran Gonzales, Luis Luna Espinoza, Lenin Maturrano Hernández, and Nilton Lincopan more...
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WHO critical-priority pathogens ,Enterobacterales ,ESBL ,Camelids ,One Health ,Genomic surveillance ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Background: The global spread of extended-spectrum β-lactamase (ESβL)-producing Escherichia coli has been considered a One Health issue that demands continuous genomic epidemiology surveillance in humans and non-human hosts. Objectives: To report the occurrence and genomic data of ESβL-producing E. coli strains isolated from South American llamas inhabiting a protected area with public access in the Andean Highlands of Peru. Methods: Two ESβL-producing E. coli strains (E. coli L1LB and L2BHI) were identified by MALDI-TOF. Genomic DNAs were extracted and sequenced using the Illumina NextSeq platform. De novo assembly was performed by CLC Genomic Workbench and in silico prediction was accomplished by curated bioinformatics tools. SNP-based phylogenomic analysis was performed using publicly available genomes of global E. coli ST10. Results: Escherichia coli L1LB generated a total of 4 000 11 and L2BHI a total of 4 002 54 paired-end reads of ca.164 × and ca. 157 ×, respectively. Both E. coli strains were assigned to serotype O8:H4, fimH41, and ST10. The blaCTX-M-65 ESβL gene, along with other medically important antimicrobial resistance genes, was predicted. Broad virulomes, including the presence of the astA gene, were confirmed. The phylogenomic analysis revealed that E. coli L1LB and L2BHI strains are closely related to isolates from companion animals and human hosts, as well as environmental strains, previously reported in North America, South America, Africa, and Asia. Conclusion: Presence of ESβL-producing E. coli ST10 in South American camelids with historical and cultural importance supports successful expansion of international clones of priority pathogens in natural areas with public access. more...
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- 2024
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9. In vitro activity of ceftazidime-avibactam against Gram-negative strains in Chile 2015–2021
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Luis C. Torres-Castillo, Cecil Fandiño, María-Paz Ramos, Jorge A. Ramos-Castaneda, María L. Rioseco, and Chrystal Juliet
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Ceftazidime/avibactam ,Enterobacterales ,Carbapenem-resistant Enterobacterales ,Gram-negative bacteria ,Pseudomonas aeruginosa ,Antimicrobial resistance ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: Ceftazidime-avibactam (CAZ-AVI) combines ceftazidime and a reversible β-lactamase inhibitor that has shown activity against multidrug-resistant (MDR) Enterobacterales and P. aeruginosa. Using data from the Antimicrobial Testing Leadership and Surveillance program (ATLAS), this study examined the in vitro antimicrobial activity of CAZ-AVI and other antibiotics against Gram-negative bacteria collected from Chilean hospitals between 2015 and 2021. Methods: Clinical isolates of Enterobacterales and P. aeruginosa were collected from three medical centres in Chile. Blood, abdominal fluid, urine, soft tissues, and respiratory tract samples were obtained from infected patients. Minimum inhibitory concentrations using the broth microdilution method were determined for susceptibility testing, and the Clinical and Laboratory Standards Institute (CLSI) breakpoints were used for interpreting the results. Extended-spectrum β-lactamases (ESBL) and carbapenemase genes were also detected through polymerase chain reaction. Results: A total of 2600 Enterobacterales and 836 P. aeruginosa were analysed. CAZ-AVI was the antibiotic with the highest in vitro activity against Enterobacterales (99.72%). The incidence of carbapenem-resistant Enterobacterales (CRE) was 1.5% (n = 39), and the antibiotics with the best in vitro activity were tigecycline (92.31%), CAZ-AVI (88.57%), and amikacin (79.49%). CAZ-AVI was the antibiotic with the best activity against ESBL-producing Enterobacterales (99.34%) and MDR Enterobacterales (99.31%). For KPC-producing Enterobacterales, susceptibility to amikacin was 100%, whereas susceptibility to CAZ-AVI was 91.67%. Regarding MDR and difficult-to-treat resistance P. aeruginosa, 44.83% and 38.99% were susceptible to CAZ-AVI, respectively. Conclusion: CAZ-AVI shows excellent in vitro activity against Enterobacterales in general, CRE, ESBL-producing Enterobacterales, and KPC-producing Enterobacterales. CAZ-AVI is also an option against MDR P. aeruginosa. more...
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- 2023
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10. In vitro activity of ceftazidime-avibactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa from sub-Saharan Africa: ATLAS Global Surveillance Program 2017–2021
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Mark G. Wise, James A. Karlowsky, Meredith A. Hackel, Mohamed Amine Harti, Bontle M.E. Ntshole, Eva Njeri Njagua, Rita Oladele, Catherine Samuel, Shameema Khan, Jeannette Wadula, Warren Lowman, Busisani W. Lembede, and Daniel F. Sahm more...
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Enterobacterales ,Pseudomonas aeruginosa ,Ceftazidime-avibactam ,Surveillance ,Antimicrobial susceptibility ,sub-Saharan Africa ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: To report the in vitro susceptibility of Enterobacterales (n = 3905) and Pseudomonas aeruginosa (n = 1,109) isolates, collected from patients in sub-Saharan Africa (four countries) in 2017–2021, to a panel of 10 antimicrobial agents with a focus on ceftazidime-avibactam activity against resistant phenotypes and β-lactamase carriers. Methods: MICs were determined by CLSI broth microdilution and interpreted using both 2022 CLSI and EUCAST breakpoints. β-lactamase genes were identified in select β-lactam-nonsusceptible isolate subsets using multiplex PCR assays. Results: Among Enterobacterales, 96.2% of all isolates were ceftazidime-avibactam-susceptible (MIC90, 0.5 µg/mL), including all serine carbapenemase-positive (n = 127), 99.6% of ESBL-positive, carbapenemase-negative (n = 730), 91.9% of multidrug resistant (MDR; n = 1817), and 42.7% of DTR (difficult-to-treat resistance; n = 171) isolates. Metallo-β-lactamase (MBL) genes were identified in most (n = 136; 91.2%) ceftazidime-avibactam-resistant isolates (3.5% of all Enterobacterales isolates). Ceftazidime-avibactam percent susceptible values ranged from 99.5% (Klebsiella species other than Klebsiella pneumoniae) to 92.5% (K. pneumoniae) for the various Enterobacterial taxa examined. Greater than 90% of Enterobacterales isolates from each country (Cameroon, Ivory Coast, Nigeria, South Africa) were ceftazidime-avibactam-susceptible. Among P. aeruginosa, 88.9% of all isolates were ceftazidime-avibactam-susceptible (MIC90, 16 µg/mL). Most (88.5%) MBL-negative, meropenem-resistant (n = 78), 68.1% of MDR (n = 385), and 19.2% of DTR isolates (n = 99) were ceftazidime-avibactam-susceptible. MBL genes were identified in 43.1% of ceftazidime-avibactam-resistant isolates (n = 53; 4.8% of all P. aeruginosa isolates). Country-specific ceftazidime-avibactam percent susceptible values for P. aeruginosa ranged from 94.1% (Cameroon) to 76.2% (Nigeria). Conclusion: Reference in vitro antimicrobial susceptibility testing demonstrated that most recent Enterobacterales (96%) and P. aeruginosa (89%) clinical isolates from four sub-Saharan African countries were ceftazidime-avibactam susceptible. more...
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- 2023
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11. Faecal carriage of multidrug-resistant and extended-spectrum β-lactamase-producing Enterobacterales in people living with HIV in Yaoundé, Cameroon
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Brice Davy Dimani, Raspail Carrel Founou, Jessica Ravalona Zemtsa, Aurélia Mbossi, Patrice Landry Koudoum, Luria Leslie Founou, Charles Kouanfack, and Lucien Honoré Etame Sone
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Antibiotic resistance ,Enterobacterales ,HIV ,ESBLs ,Gut microbiome ,Cameroon ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: Antibiotic resistance (AR) is a global health issue with multidimensional repercussions. There is a paucity of data regarding the molecular epidemiology of multidrug-resistant Enterobacterales (MDR-E) and extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) in Africa, especially among people living with HIV (PLHIV). This study aimed at determining the prevalence, risk factors, phenotypic and genotypic profiles of MDR-E and ESBL-PE isolated from PLHIV in Yaoundé, Cameroon. Methods: In total, samples were collected from 185 PLHIV during a three-month period (April–June 2021) at the Yaoundé Central Hospital. Stool samples and rectal swabs were collected and cultured on MacConkey agar. The API 20E kit was used for the phenotypic identification of the isolates, whereas antibiotic susceptibility testing was performed using the Kirby-Bauer disk diffusion method. The ß-lactamase genes and genotypic relatedness were studied by PCR and ERIC-PCR, respectively. Results: The prevalence of MDR-E among PLHIV was 81%, of which 39% were ESBL-PE. A high level of resistance to fosfomycin (89%), chloramphenicol (63%), and gentamicin (56%) was observed. Escherichia coli was the predominant MDR non-ESBL-PE (80.8%) and MDR ESBL-PE (73.77%). The principal ß-lactamases genes in MDR non-ESBL and MDR ESBL-PE were blaTEM (62.90%) and blaCTX-M (40.86%), respectively. Genetic fingerprinting revealed high genetic relatedness among E. coli isolates. Conclusion: This study shows a high prevalence of MDR-E and ESBL-PE in the gut of PLHIV in Yaoundé, with blaTEM and blaCTX-M being the most prevalent. It demonstrates the need to strengthen real-time surveillance of these resistant bacteria in order to improve management of infection among PLHIV. more...
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- 2023
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12. Genomic analysis of fluoroquinolone-resistant Leclercia adecarboxylata carrying the ISKpn19-orf-qnrS1-ΔIS3-blaLAP-2 module in a synanthropic pigeon, Brazil
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Elder Sano, Herrison Fontana, Fernanda Esposito, Brenda Cardoso, Bruna Fuga, Gladyston C.V. Costa, Tatiana C.M. Bosqueiro, Juliana A. Sinhorini, Lilian D. Orico, Eduardo de Masi, Caroline C. Aires, and Nilton Lincopan more...
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Enterobacterales ,Fluoroquinolone resistance ,Emerging pathogens ,Resistome ,Urban wildlife ,Genomic surveillance ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: The aim of this study was to perform a genomic investigation of a multiple fluoroquinolone-resistant Leclercia adecarboxylata strain isolated from a synanthropic pigeon in São Paulo, Brazil. Methods: Whole-genome sequencing was performed using an Illumina platform, and in silico deep analyses of the resistome were performed. Comparative phylogenomics was conducted using a global collection of publicly available genomes of L. adecarboxylata strains isolated from human and animal hosts. Results: L. adecarboxylata strain P62P1 displayed resistance to human (norfloxacin, ofloxacin, ciprofloxacin, and levofloxacin) and veterinary (enrofloxacin) fluoroquinolones. This multiple quinolone-resistant profile was associated with mutations in the gyrA (S83I) and parC (S80I) genes and the presence of the qnrS gene within an ISKpn19-orf-qnrS1-ΔIS3-blaLAP-2 module, previously identified in L. adecarboxylata strains isolated from pig feed and faeces in China. Genes associated with arsenic, silver, copper, and mercury resistance were also predicted. Phylogenomic analysis revealed clustering (378–496 single nucleotide polymorphism differences) with two L. adecarboxylata strains isolated from human and fish sources in China and Portugal, respectively. Conclusions: L. adecarboxylata is a Gram-negative bacterium of the Enterobacterales order and is considered an emergent opportunistic pathogen. Since L. adecarboxylata has adapted to human and animal hosts, genomic surveillance is highly recommended, in order to identify the emergence and spread of resistant lineages and high-risk clones. In this regard, this study provides genomic data that can help clarify the role of synanthropic animals in the dissemination of clinically relevant L. adecarboxylata within a One Health context. more...
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- 2023
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13. Emergence of blaSHV-12 and qnrS1 encoded on IncX3 plasmids: Changing epidemiology of extended-spectrum ß-lactamases among Enterobacterales isolated from broilers
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Magdalena Nüesch-Inderbinen, Lore Heyvaert, Nicole Cernela, Katrin Zurfluh, Michael Biggel, and Roger Stephan
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IncX3 ,SHV-12 ,QnrS1 ,Broilers ,Enterobacterales ,Extended-spectrum ß-lactamases ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: The occurrence of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales in broilers represents a risk to public health because of the possibility of transmission of ESBL producers and/or blaESBL genes via the food chain or within settings where human-animal interfaces exist. Methods: This study assessed the occurrence of ESBL producers among faecal samples of broilers at slaughter. Isolates were characterised by multilocus sequence typing, antimicrobial susceptibility testing, and whole-genome sequencing. Results: The flock prevalence, determined by sampling crates of 100 poultry flocks, was 21%. The predominant blaESBL gene was blaSHV-12, identified in 92% of the isolates. A variety of Escherichia coli and Klebsiella pneumoniae sequence types (STs) were identified, including extraintestinal pathogenic E. coli ST38, avian pathogenic E. coli ST10, ST93, ST117, and ST155, and nosocomial outbreak clone K. pneumoniae ST20. Whole-genome sequencing was used to characterise a subset of 15 isolates, including 6 E. coli, 4 K. pneumoniae, 1 Klebsiella grimontii, 1 Klebsiella michiganensis, 1 Klebsiella variicola, and 1 Atlantibacter subterranea. Fourteen isolates carried identical or closely related 46338–54929 bp IncX3 plasmids encoding blaSHV-12 and qnrS1. One E. coli isolate carried a 46338 bp IncX3 plasmid, which was integrated chromosomally into ydbD. Conclusions: The blaSHV-12 gene has replaced the previously predominant blaCTX-M-1 in ESBL-producing Enterobacterales from broilers in Switzerland. Broilers may play a role in the dissemination of blaSHV-12 and qnrS1 associated with epidemic IncX3 plasmids, representing a risk to human and animal health. more...
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- 2023
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14. Clinical efficacy of ertapenem vs. other carbapenems for the treatment of extended-spectrum-β-lactamase-producing Enterobacterales infection: A systematic review and meta-analysis
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Po-Yu Huang, Chi-Kuei Hsu, Ting-Hui Liu, Jheng-Yan Wu, Hung-Jen Tang, Ya-Wen Tsai, Chih-Cheng Lai, and Yi-Hsin Chang
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Enterobacterales ,Extended-spectrum-β-lactamase ,Doripenem ,Ertapenem ,Imipenem ,Meropenem ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objective: Both ertapenem and other carbapenems, including imipenem, meropenem, and doripenem, are recommended in the treatment of extended-spectrum-β-lactamase (ESBL)-producing Enterobacterales infection. However, whether ertapenem is as effective as other carbapenems for ESBL-producing Enterobacterales remains unclear. Therefore, this meta-analysis was conducted to compare the clinical efficacy of ertapenem versus other carbapenems in the treatment of ESBL-producing Enterobacterales infection. Methods: PubMed, Web of Science, and Cochrane Library were searched from their inception to 29 November 2022. Only studies comparing ertapenem and other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections were included. Results: A total of six studies meeting selection criteria were identified. Overall, ertapenem was associated with a significantly lower 30-d mortality when compared with other carbapenems (10.7% [46/431] vs. 17.7% [104/586]; risk ratio [RR], 0.61; 95% CI: 0.40–0.91). The ertapenem group exhibited a significantly shorter length of hospital stay than the other carbapenem groups (mean differences, -6.02 d; 95% CI, -9.39 to -2.64). No significant differences were noted between ertapenem and other carbapenem groups in terms of rates of clinical cure or improvement (RR, 1.11; 95% CI: 0.97–1.25) and microbiological eradication (RR, 1.01; 95% CI: 0.97–1.06). Conclusions: Ertapenem could be as effective as other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections. more...
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- 2023
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15. Evaluation of ceftolozane-tazobactam susceptibility on a French nationwide collection of Enterobacterales
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Agnès B. Jousset, Sandrine Bernabeu, Cécile Emeraud, Rémy A. Bonnin, Alexandra Lomont, Jean Ralph Zahar, Audrey Merens, Christophe Isnard, Nathalie Soismier, Eric Farfour, Vincent Fihman, Nicolas Yin, Olivier Barraud, Hervé Jacquier, Anne-Gaëlle Ranc, Frédéric Laurent, Stéphane Corvec, Louise Ruffier d'Epenoux, Emmanuelle Bille, Nicolas Degand, Chloé Plouzeau, Thomas Guillard, Vincent Cattoir, Asaf Mizrahi, Antoine Grillon, Frédéric Janvier, Cécile Le Brun, Marlène Amara, Mathilda Bastide, Alban Lemonnier, and Laurent Dortet more...
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Ceftolozane-tazobactam ,ESBL ,Carbapenemase ,Enterobacterales ,Epidemiology ,France ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: Ceftolozane-tazobactam (C/T) proved its efficacy for the treatment of infections caused by non-carbapenemase producing Pseudomonas aeruginosa and Enterobacterales. Here, we aimed to provide susceptibility data on a large series of Enterobacterales since the revision of EUCAST categorization breakpoints in 2020. Methods: First, C/T susceptibility was determined on characterized Enterobacterales resistant to third generation cephalosporins (3GCs) (extended spectrum β-lactamase [ESBL] production or different levels of AmpC overexpression) (n = 213) and carbapenem-resistant Enterobacterales (CRE) (n = 259), including 170 carbapenemase producers (CPE). Then, 1632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by E-test® (biomérieux) and broth microdilution (BMD) (Sensititre™, Thermo Scientific) to perform method comparison. Results: Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with important variation depending on the resistance mechanism: 93% vs. 13% susceptibility for CTX-M and SHV-ESBL producers, respectively. Only 20% of the CRE were susceptible to C/T. Among CPE, 80% of OXA-48-like producers were susceptible to C/T, whereas all metallo-β-lactamase producers were resistant. The prospective study revealed that 95.6% of clinical isolates were susceptible to C/T. Method comparison performed on these 1632 clinical isolates demonstrated 99% of categorization agreement between MIC to C/T determined by E-test® in comparison with the BMD (reference) and only 74% of essential agreement. Conclusion: Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers, and ESBL-producing Escherichia coli but is less active against ESBL-producing Klebsiella pneumoniae, and CRE. E-test® led to an underestimation of the MICs in comparison to the BMD reference. more...
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- 2023
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16. Complete genome sequence and antimicrobial resistance analysis of ESBL-producing Shigella sonnei carrying small cryptic plasmids isolated in northern Italy
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Stefano Amadesi, Simone Ambretti, Tiziana Lazzarotto, and Paolo Gaibani
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Multidrug resistance ,Enterobacterales ,cryptic plasmids ,hybrid approach ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: Herein, we sequenced and assembled the genome of a Shigella sonnei isolate carrying several small plasmids using a hybrid approach that combined Oxford Nanopore Technologies and Illumina platforms. Methods: Whole-genome sequencing was conducted using the Illumina iSeq 100 and Oxford Nanopore MinION systems, and the resulting reads were used for hybrid genome assembly via Unicycler. Coding sequences were annotated using RASTtk, while genes involved in antimicrobial resistance and virulence were identified using AMRFinderPlus. Plasmid nucleotide sequences were aligned to the NCBI non-redundant database using BLAST, and replicons were identified using PlasmidFinder. Results: The genome consisted of 1 chromosome (4 801 657 bp), 3 major plasmids (212 849 bp, 86 884 bp, and 83 425 bp, respectively) and 12 small cryptic plasmids (ranging from 8390 bp to 1822 bp). BLAST analysis revealed that all plasmids were highly similar to previously deposited sequences. Genome annotation predicted 5522 coding regions, including 19 antimicrobial resistance genes and 17 virulence genes. Four of the antimicrobial resistance genes were located in small plasmids, and four of the virulence genes were located in a large virulence plasmid. Conclusion: The presence of antimicrobial resistance genes in small cryptic plasmids may represent an overlooked mechanism for the propagation of these genes among bacterial populations. Our work provides new data on these elements that may inform the development of new strategies to control the spread of extended spectrum β-lactamase–producing bacterial strains. more...
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- 2023
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17. Activity of Ceftolozane-Tazobactam Against Gram-Negative Isolates from Australia and New Zealand as part of the PACTS Surveillance 2016-2018
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Dee Shortridge, Jennifer Streit, Michael Pfaller, Merrin Tulloch, Wei-Ting Chen, and Mariana Castanheira
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Ceftolozane-tazobactam ,Enterobacterales ,Pseudomonas aeruginosa ,Australia, New Zealand ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: Ceftolozane-tazobactam (C-T) is an anti-pseudomonal cephalosporin combined with a well-described β-lactamase inhibitor. Ceftolozane-tazobactam has enhanced activity against Pseudomonas aeruginosa, and activity against Enterobacterales isolates that produce extended-spectrum β-lactamases (ESBLs) or AmpC cephalosporinases. In this study, we analysed the susceptibility of Gram-negative isolates to C-T and comparators collected in Australia and New Zealand from 2016 to 2018 as part of the Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) surveillance. Methods: A total of 1693 nonduplicate Enterobacterales and 435 P. aeruginosa isolates were collected prospectively from hospitalized patients in six medical centres in Australia and two in New Zealand. Susceptibilities (S) to C-T and comparators were determined using broth microdilution. EUCAST breakpoints were used. Isolates with multi-drug resistant (MDR), extensively drug resistant (XDR), extended-spectrum β-lactamase non-carbapenem resistant (ESBL, non-CRE) phenotype, and CRE were analysed. Results: For P. aeruginosa, 97.5% were S to C-T while 89.9% were S to meropenem. According to EUCAST criteria, 86.4% were susceptible-increased exposure to piperacillin-tazobactam. MDR and XDR P. aeruginosa isolates had 76.7% and 65.4% S to C-T, respectively; 34.9% and 19.2% S to meropenem, respectively; and 23.3% and 15.4% were susceptible-increased exposure to piperacillin-tazobactam, respectively. Meropenem (99.8% S), amikacin (99.1% S), and C-T (96.5% S) were the most active against Enterobacterales. Susceptibilities to C-T were 94.3% for ESBL, non-CRE phenotype, and 78.4% for MDR isolates. Only three CRE and five XDR isolates were identified. Conclusions: These in vitro data indicate that C-T is a potent antimicrobial with activity against MDR and XDR P. aeruginosa, as well as ESBL, non-CRE phenotype isolates and MDR Enterobacterales. more...
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- 2022
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18. Emergence of OXA-484, an OXA-48–type beta-lactamase, in Switzerland
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Jacqueline Findlay, Juan Bosch Duran, Laurent Poirel, and Patrice Nordmann
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Carbapenemase ,Enterobacterales ,OXA-48-type ,Plasmid ,Microbiology ,QR1-502 - Published
- 2023
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19. Antimicrobial susceptibility testing of clinical isolates of Gram-negative bacilli collected in Morocco by the ATLAS Global Surveillance Program from 2018 to 2020
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James A. Karlowsky, Samuel K. Bouchillon, Amina Benaouda, Nabila Soraa, Khalid Zerouali, Naglaa Mohamed, Taha Alami, and Daniel F. Sahm
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Morocco ,Enterobacterales ,Pseudomonas aeruginosa ,Acinetobacter baumannii ,Ceftazidime-avibactam ,ATLAS ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: To report reference method antimicrobial susceptibility testing results for recent clinical isolates of Gram-negative bacilli from Morocco. Methods: CLSI (Clinical and Laboratory Standards Institute) broth microdilution antimicrobial susceptibility testing was performed by a central laboratory for isolates of Enterobacterales (n = 810), Pseudomonas aeruginosa (n = 321), and Acinetobacter baumannii (n = 191) collected in 2018–2020 by three hospital laboratories in Morocco. MICs were interpreted using both CLSI (2021) and EUCAST (European Committee on Antimicrobial Susceptibility Testing) (2021) breakpoints. Molecular testing for β-lactamase genes was performed on isolates meeting defined screening criteria. Results: Most isolates of Enterobacterales were susceptible (CLSI/EUCAST breakpoints) to amikacin (98.0%/96.2%), ceftazidime-avibactam (94.8%/94.8%), and meropenem (92.5%/94.2%). Of Enterobacterales isolates eligible for β-lactamase gene screening (n = 210), 174 were ESBL-positive, 40 were metallo-β-lactamase-positive (all NDM), 39 were serine carbapenemase-positive (all OXA); and 7 isolates carried both OXA-48 and NDM-1. Amikacin (89.1%/89.1%) and ceftazidime-avibactam (88.2%/88.2%) were the most active agents tested against P. aeruginosa. Applying CLSI and EUCAST breakpoints, MDR rates were 21.9% and 29.3% for Enterobacterales and 18.4% and 21.8% for P. aeruginosa. Susceptible rates for amikacin, ceftazidime-avibactam, and meropenem were 93.2%/89.5%, 77.4%/82.3%, and 67.8%/80.2% for MDR Enterobacterales and 50.8%/57.1%, 40.7%/45.7%, and 27.1/32.9% for MDR P. aeruginosa. ≥70% of A. baumannii isolates were resistant to all agents tested (except colistin, EUCAST breakpoints only) including amikacin and meropenem. Conclusion: Newer β-lactam/β-lactamase inhibitor combinations such as ceftazidime-avibactam warrant testing and reporting for Enterobacterales and P. aeruginosa in Morocco given the presence of significant resistance to first-line β-lactams and fluoroquinolones, pervasive ESBLs and carbapenemases, and toxicity concerns associated with some second-line agents. more...
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- 2022
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20. Molecular characterization of extended-spectrum ß-lactamase producers, carbapenemase producers, polymyxin-resistant, and fosfomycin-resistant Enterobacterales among pigs from Egypt
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Mustafa Sadek, José Manuel Ortiz de la Rosa, Mustafa Ramadan, Patrice Nordmann, and Laurent Poirel
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Pigs ,ESBL ,Enterobacterales ,mcr ,Carbapenemases ,Fosfomycin ,Microbiology ,QR1-502 - Abstract
Objectives: To perform the first prospective surveillance evaluating the occurrence of genes encoding colistin resistance, fosfomycin resistance, carbapenemase, or extended-spectrum ß-lactamases (ESBLs) among Enterobacterial isolates recovered from the gut flora of pigs from Egypt. Methods: Between February and April 2020, 81 rectal swabs were collected from pigs in a slaughterhouse, Cairo, Egypt. Samples were screened for different resistance mechanisms using SuperPolymyxin, ChromID ESBL, SuperFOS, and SuperCarba selective agar plates. Antimicrobial susceptibility testing was performed for all isolates using disk diffusion and broth microdilution techniques. PCR screening was performed for ESBLs, carbapenemases, mcr, and fosA genes. Mating-out assays, multilocus sequence typing analysis, and plasmid typing were also performed. Results: A high prevalence of ESBLs, carbapenemases, fosfomycin, and colistin resistance genes was evidenced among those isolates. The predominant ESBL identified was blaCTX-M-15, followed by blaCTX-M-9. We also identified blaNDM-5 and blaOXA-244. fosA3, fosA4, and fosA6 were identified in E. coli isolates. In addition, 11 MCR-1 producers were recovered. Notably, co-occurrence of ESBL genes and mcr or fosA genes was observed. MLST analysis revealed a high clonal diversity, ruling out the dissemination of one major clone. IncFIB-type was predominantly present among ESBL and FosA producers. The blaNDM-5 gene was carried on an IncX4-type, although the blaOXA-244 gene was chromosomally located. The mcr-1 gene was carried on a diversity of plasmids (IncI2, IncX4, and IncHI2). Conclusion: These results raise serious public health concerns as Egyptian pig meat could serve as a reservoir for antimicrobial resistance genes (ARGs), leading to worldwide dissemination. more...
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- 2022
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21. Attributable mortality and excess length of stay associated with third-generation cephalosporin-resistant Enterobacterales bloodstream infections: a prospective cohort study in Suva, Fiji
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Michael J. Loftus, Tracey E.M.W. Young-Sharma, Sue J. Lee, Shitanjni Wati, Gnei Z. Badoordeen, Luke V. Blakeway, Sally M.H. Byers, Allen C. Cheng, Ben S. Cooper, Hugh Cottingham, Adam W.J. Jenney, Jane Hawkey, Nenad Macesic, Ravi Naidu, Amitesh Prasad, Vinita Prasad, Litia Tudravu, Timoci Vakatawa, Elke van Gorp, Jessica A. Wisniewski, Eric Rafai, Anton Y. Peleg, and Andrew J. Stewardson more...
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Bloodstream infection ,Enterobacterales ,Mortality ,Antimicrobial resistance ,Fiji ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: There are scant primary clinical data on antimicrobial resistance (AMR) burden from low- and middle-income countries (LMICs). We adapted recent World Health Organization methodology to measure the effect of third-generation cephalosporin resistance (3GC-R) on mortality and excess length of hospital stay in Fiji. Methods: We conducted a prospective cohort study of inpatients with Enterobacterales bloodstream infections (BSIs) at Colonial War Memorial Hospital, Suva. We used cause-specific Cox proportional hazards models to estimate the effect of 3GC-R on the daily risk (hazard) of in-hospital mortality and being discharged alive (competing risks), and we used multistate modelling to estimate the excess length of hospital stay. Results: From July 2020 to February 2021 we identified 162 consecutive Enterobacterales BSIs; 3GC-R was present in 66 (40.7%). Crude mortality for patients with 3GC-susceptible and 3GC-R BSIs was 16.7% (16/96) and 30.3% (20/66), respectively. 3GC-R was not associated with the in-hospital mortality hazard rate (adjusted hazard ratio [aHR] 1.13, 95% confidence interval [CI] 0.51–2.53) or being discharged alive (aHR 0.99, 95% CI 0.65–1.50), whereas Charlson comorbidity index score (aHR 1.62, 95% CI 1.36–1.93) and Pitt bacteraemia score (aHR 3.57, 95% CI 1.31–9.71) were both associated with an increased hazard rate of in-hospital mortality. 3GC-R was associated with an increased length of stay of 2.6 days (95% CI 2.5–2.8). 3GC-R was more common among hospital-associated infections, but genomics did not identify clonal transmission. Conclusion: Patients with Enterobacterales BSIs in Fiji had high mortality. There were high rates of 3GC-R, which was associated with increased hospital length of stay but not with in-hospital mortality. more...
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- 2022
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22. Clinical epidemiology of carbapenem-resistant Enterobacterales in the Greater Houston region of Texas: a 6-year trend and surveillance analysis
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Bekana K. Tadese, Charles Darkoh, Stacia M. DeSantis, Osaro Mgbere, and Kayo Fujimoto
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CRE ,Surveillance ,Carbapenemase ,KPC ,Enterobacterales ,Healthcare-associated infections ,Microbiology ,QR1-502 - Abstract
Objectives: Carbapenem-resistant Enterobacterales (CRE) remain an urgent public health priority in the United States. CRE poses a major threat to patients in healthcare and a potential risk to the community. This study examined the epidemiological trends, clinical, and microbiological data of CRE in the Greater Houston region of Texas. Methods: A multi-institutional retrospective observational study was conducted using surveillance data collected from 2015 to 2020. Predictors of incidence rates of CRE were determined by a negative binomial regression fit using a generalized estimation equation. Results: Over a 6-year period, 4236 CRE cases were reported, of which Klebsiella pneumoniae accounted for 84.8%. The results show a steady increase in CRE cases, with a sharp rise since 2018. The majority of carbapenemase-producing Enterobacterales were Klebsiella pneumoniae carbapenemase (KPC)-producing (77.2%), followed by other rare carbapenemases, which includes OXA-48, NDM, IMP, VIM, coproduction of KPC with OXA-48, KPC with NDM, and NDM with OXA-48. Acute care hospitals (ACH) accounted for 68.5% of the source of CRE cases. The incidence rate of CRE cases reported from ACH and long-term acute care (LTAC) facilities was 1.16 times that of long-term care facilities (adjusted rate ratio [ARR] = 1.16, 95% confidence interval [CI]:1.04–1.30). The incidence rate of CRE among patients with indwelling devices was 15% (ARR = 0.85, 95% CI: 0.79–0.92) lower than that of patients without indwelling devices. Conclusion: The rise in the rate of CRE cases despite aggressive infection prevention and control strategies in the region is alarming. Evaluating and improving the current infection control strategies may be warranted. more...
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- 2022
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23. In vitro activity of aztreonam/avibactam against isolates of Enterobacterales collected globally from ATLAS in 2019
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Gian Maria Rossolini, Gregory Stone, Michal Kantecki, and Francis F. Arhin
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Enterobacterales ,ATM-AVI ,Metallo-β-lactamase ,ATLAS ,Microbiology ,QR1-502 - Abstract
Objectives: : Infections caused by drug-resistant Enterobacterales including those producing metallo-β-lactamases (MBLs) are particularly challenging due to limited therapeutic options. The drug combination aztreonam/avibactam (ATM-AVI) is under clinical development for treating serious infections caused by these strains. This study assessed the in vitro activity of ATM-AVI against Enterobacterales isolates collected globally in the ATLAS surveillance programme in 2019. Methods: : Clinical isolates of Enterobacterales (N = 18 713) including Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Serratia marcescens collected from 232 sites in 2019 were analysed. Antimicrobial susceptibility testing was performed by reference broth microdilution. A pharmacokinetic/pharmacodynamic based breakpoint of 8 mg/L was considered for ATM-AVI activity. Results: : ATM-AVI demonstrated potent antimicrobial activity against all Enterobacterales, with 99.9% isolates inhibited at MIC ≤8 mg/L (MIC90, 0.25 mg/L). MICs ≤8 mg/L (>99.0%) were noted for ATM-AVI across regions worldwide. Among other antimicrobials, amikacin, colistin, imipenem, meropenem, and tigecycline were also active (susceptibility >85.0%) against Enterobacterales. Activity of ATM-AVI was sustained against multidrug-resistant, extended-spectrum β-lactamase producing, and carbapenem-resistant isolates (susceptibility >99%; MIC90, 0.25–0.5 mg/L). Importantly, potent activity for ATM-AVI (>99.0%; MIC90, 0.5 mg/L) was noted among MBL-positive isolates and those producing other carbapenemases, such as KPC and OXA-48. Conclusion: : Our results demonstrated that ATM-AVI was highly active against a recent collection of Enterobacterales isolates, including those producing MBLs either alone or in combination with other carbapenemases. Thus, ATM-AVI represents a potential option for treating infections caused by antibiotic-resistant Enterobacterales including MBL-producing strains. more...
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- 2022
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24. Epidemiology and genotypic characteristics of carbapenem resistant Enterobacterales in Henan, China: a multicentre study
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Nan Jing, Wenjuan Yan, Qi Zhang, Youhua Yuan, Xidian Wei, Wenmin Zhao, Shengqiang Guo, Limin Guo, Yuan Gao, Liang Zhao, Caiqin Shi, and Yi Li
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Enterobacterales ,Carbapenemase ,KPC-2 ,ST11 ,Colistin resistance ,mcr-1 ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: : To identify the carbapenemase and colistin resistance genes and epidemiological status of carbapenem-resistant Enterobacterales (CRE) among 7 secondary and 11 tertiary hospitals in Henan province, China. Methods: : CRE isolates and clinical data of infected patients were collected from 7 secondary and 11 tertiary hospitals in Henan from July to September 2019 and analysed retrospectively. Polymerase chain reaction (PCR) and gene sequencing were performed to detect carbapenemase and colistin resistance genes; multilocus sequence typing was also performed. Results: : In total, 238 nonduplicate CRE isolates were collected mainly from the respiratory tract (54.20%) and blood (18.91%) of CRE-infected patients, half of them aged >65 years (45.80%). Carbapenem-resistant Klebsiella pneumoniae (CRKP) was the most common CRE (184 isolates, 77.31%) with constituent ratios of 84.38% and 72.54% in secondary and tertiary hospitals, respectively. In 184 CRKP isolates, blaKPC-2 (89.13%) was the dominant carbapenemase gene, and ST11 (71.74%) was the most prevalent sequence type (ST), with constituent ratios of 83.95% and 62.14% in secondary and tertiary hospitals, respectively. In 29 carbapenem-resistant Escherichia coli (CREC) isolates, blaNDM-5 (58.62%) and ST2 (31.03%) were prevalent. Four CRKP isolates and one CREC isolate were colistin-resistant and carried the plasmid-mediated mcr-1 gene. Conclusion: : Our results showed a wide spread of CRKP-ST11 with KPC-2 carbapenemase in the analysed 18 hospitals. The CRKP constituent ratio, CRKP-STs, and CREC carbapenemase genes between secondary and tertiary hospitals showed significant differences. The emergence of a colistin-resistant CRKP with plasmid-mediated resistance gene mcr-1 is of serious concern due to the limited treatment options. more...
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- 2022
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25. In vitro activity of ceftazidime/avibactam against Gram-negative strains in Colombia 2014–2018
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Elkin V. Lemos-Luengas, MD, PhD, Sixta Rentería-Valoyes, MD, Paola Cárdenas-Isaza, MD, MSc, and Jorge A. Ramos-Castaneda, PhD
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Ceftazidime/avibactam ,Enterobacterales ,Carbapenem-resistant Enterobacterales ,Gram-negative bacteria ,Pseudomonas aeruginosa ,Antimicrobial resistance ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: Ceftazidime/avibactam (CAZ/AVI) has shown in vitro activity against multidrug-resistant (MDR) Gram-negative bacteria, especially Enterobacterales and carbapenem-resistant Pseudomonas aeruginosa. However, in vitro activity of CAZ/AVI against Gram-negative bacteria in Colombian hospitals is still unknown. The study aimed to analyse the in vitro antimicrobial activity of CAZ/AVI against Gram-negative bacteria collected from hospitals in Colombia using the Antimicrobial Testing Leadership and Surveillance (ATLAS) database. Methods: Enterobacterales and P. aeruginosa samples were obtained from four hospitals in Colombia between 2014 and 2018. Samples of blood, abdominal fluid, urine, soft tissues, and respiratory tract were collected from adult and paediatric patients. The 2020 Clinical and Laboratory Standards Institute (CLSI) breakpoints were used for the interpretation of susceptibility. Meropenem-non-susceptible Enterobacterales and P. aeruginosa isolates were screened for extended-spectrum β-lactamase (ESBL) production. Isolates that were positive for ESBL activity were examined by PCR for detecting genotypic resistance. Results: A total of 2005 Enterobacterales were isolated; 29.28% were not susceptible to levofloxacin, 29.14% to aztreonam, and 25.19% to cefepime. The CAZ/AVI was the antibiotic with the best susceptibility against carbapenem-resistant Enterobacterales (CRE) (94.64%), non-metallo-β-lactamase(MBL)-producing Enterobacterales (98.06%), and MDR Enterobacterales (98.36%). For carbapenem-resistant P. aeruginosa, in vitro activity of CAZ/AVI was 59.26%, and 50% for non-MBL-producing P. aeruginosa. Conclusion: CAZ/AVI shows excellent in vitro activity against MDR Enterobacterales and CRE. For MDR P. aeruginosa and carbapenem-resistant P. aeruginosa, in vitro activity of CAZ/AVI was lower compared to the activity against Enterobacterales, but CAZ/AVI was the antibiotic with the best activity. more...
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- 2022
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26. Emergent Escherichia coli of the highly virulent B2-ST1193 clone producing KPC-2 carbapenemase in ready-to-eat vegetable.
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Dantas K, Melocco G, Esposito F, Fontana H, Cardoso B, and Lincopan N
- Abstract
Objectives: Critical priority carbapenem-resistant pathogens constitute a worldwide public health problem. Escherichia coli ST1193 is an emerging high-risk clone that demonstrates prolonged gut persistence, and association with community-onset urinary and bloodstream infections. The purpose of this study is to report microbiological and genomic data on the emergence of KPC-2-producing E. coli ST1193 in ready-to-eat (RTE) vegetable., Methods: RTE vegetables were purchased from markets in southeastern Brazil. Epiphytic and endophytic Gram-negative bacteria displaying resistance to broad-spectrum beta-lactams were identified by MALDI-TOF. WGS was conducted using the Illumina NextSeq platform. Antimicrobial susceptibility, conjugation, and acid tolerance assays were performed. Virulence behavior was evaluated using the Galleria mellonella infection model., Results: Epiphytic KPC-2-producing E. coli belonging to pandemic ST1193 was identified in RTE arugula. Genomic analysis predicted clinically relevant genes conferring resistance to β-lactams, fluoroquinolones, hazardous heavy metals, pesticides, disinfectants, and chlorine sanitizer. The bla
KPC-2 gene was carried by a conjugative IncF plasmid. Resistance of E. coli KPC-2/ST1193 at pH 2.0 was confirmed, being associated with gadWX and ibaG pH tolerance genes, supporting survival to stomach acid prior to reaching small intestine, and potential for a dietary mode of host colonization. Virulent behavior was supported by wide virulome of the highly virulent phylogroup B2, whereas cgSNP-based phylogenomics revealed clonal relationship with healthcare-associated lineages circulating in the United States, China, Mexico, France and Brazil., Conclusions: We report the occurrence of KPC-2-producing E. coli of the highly virulent B2-ST1193 clone in RTE vegetable, highlighting a possible route of dissemination of WHO priority pathogens to humans., Competing Interests: Declaration of Interest Statement The authors Karine Dantas, Gregory Melocco, Fernanda Esposito, Herisson Fontana, Brenda Cardoso, and Nilton Lincopan, declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper entitled “Emergent Escherichia coli of the highly virulent B2-ST1193 clone producing KPC-2 carbapenemase may be transmissible through ready-to-eat vegetable”, (Copyright © 2024. Published by Elsevier Ltd.) more...- Published
- 2024
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27. In vitro activity of ceftazidime/avibactam and comparators against carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa isolates collected globally between 2016 and 2018
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Pattarachai Kiratisin, Krystyna Kazmierczak, and Gregory G. Stone
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Ceftazidime/avibactam ,Enterobacterales ,Pseudomonas aeruginosa ,Antimicrobial susceptibility ,Carbapenemase ,Metallo-β-lactamase ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: This study reports the antimicrobial activity of ceftazidime/avibactam (CZA) and comparators against carbapenemase-producing Enterobacterales (N = 1992) and carbapenemase-producing Pseudomonas aeruginosa (N = 784) collected in Africa/Middle East, Asia/South Pacific, Europe and Latin America (2016–2018).Methods: Minimum inhibitory concentrations (MICs) and susceptibility were determined using broth microdilution methodology and EUCAST breakpoints. Carbapenemase-encoding genes were detected using multiplex PCR.Results: No isolates of carbapenemase-producing, metallo-β-lactamase (MBL)-negative Enterobacterales from Africa/Middle East or Latin America were resistant to CZA; resistance rates in Europe and Asia/South Pacific were ≤4.5%. Colistin had the lowest resistance rate among MBL-positive isolates (6.0–11.4%). Enterobacterales isolates collected in Latin America predominantly carried a KPC carbapenemase (77.6%), whereas in Africa/Middle East OXA-48-like carbapenemases were most frequently detected (55.9%), and in Asia/South Pacific most isolates carried NDM carbapenemases (56.2%). Among all Enterobacterales carrying KPC carbapenemases, the lowest rate of resistance was to CZA (1.5%), and among isolates carrying NDM carbapenemases it was to colistin (10.8%). Among carbapenemase-producing, MBL-negative P. aeruginosa, resistance rates to CZA were 8.6% for isolates collected in Europe and 53.2% in Latin America. Isolates in each region most frequently carried VIM carbapenemases, ranging from 41.7% of isolates in Asia/South Pacific to 86.2% in Africa/Middle East. No P. aeruginosa carrying KPC or NDM carbapenemases and 1.0% of isolates carrying GES carbapenemases were resistant to colistin.Conclusion: Given the limited therapeutic options to treat infections caused by carbapenemase-positive Enterobacterales and P. aeruginosa, continued surveillance of CZA activity as well as agents such as colistin is crucial. more...
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- 2021
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28. Expansion of KPC-producing Enterobacterales in four large hospitals in Hanoi, Vietnam
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Tran Dieu Linh, Nguyen Hoai Thu, Keigo Shibayama, Masato Suzuki, LayMint Yoshida, Pham Duy Thai, Dang Duc Anh, Tran Nhu Duong, Hong Son Trinh, Vu Phuong Thom, Luu Thi Vu Nga, Nguyen Thi Kim Phuong, Bui Thanh Thuyet, Timothy R. Walsh, Le Viet Thanh, Anne-Laure Bañuls, H. Rogier van Doorn, Tran Van Anh, and Tran Huy Hoang more...
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Carbapenem resistance ,KPC ,Enterobacterales ,Vietnam ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: : The incidence of carbapenem resistance among nosocomial Gram-negative bacteria in Vietnam is high and increasing, including among Enterobacterales. In this study, we assessed the presence of one of the main carbapenemase genes, blaKPC, among carbapenem-resistant Enterobacterales (CRE) from four large hospitals in Hanoi, Vietnam, between 2010 and 2015, and described their key molecular characteristics. Methods: : KPC-producing Enterobacterales were detected using conventional PCR and were further analysed using S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blotting and whole-genome sequencing (WGS) for sequence typing and genetic characterisation. Results: : blaKPC genes were detected in 122 (20.4%) of 599 CRE isolates. blaKPC-carrying plasmids were diverse in size. Klebsiella pneumoniae harbouring blaKPC genes belonged to ST15 and ST11, whereas KPC-producing Escherichia coli showed more diverse sequence types including ST3580, ST448, ST709 and ST405. Genotypic relationships supported the hypothesis of circulation of a population of ‘resident’ resistant bacteria in one hospital through the years and of transmission among these hospitals via patient transfer. WGS results revealed co-carriage of several other antimicrobial resistance genes and three different genetic contexts of blaKPC-2. Among these, the combination of ISEcp1–blaCTX-M and ISKpn27–blaKPC–ΔISKpn6 on the same plasmid is reported for the first time. Conclusion: : We describe the dissemination of blaKPC-expressing Enterobacterales in four large hospitals in Hanoi, Vietnam, since 2010, which may have started earlier, along with their resistance patterns, sequence types, genotypic relationship, plasmid sizes and genetic context, thereby contributing to the overall picture of the antimicrobial resistance situation in Enterobacterales in Vietnam. more...
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- 2021
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29. Phylogenomic analysis of CTX-M-15–producing Enterobacter hormaechei belonging to the high-risk ST78 from animal infection: another successful One Health clone?
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Brenda Cardoso, Fábio P. Sellera, Elder Sano, Fernanda Esposito, Lourdes A.V. Seabra, Milton R. Azedo, Fabio C. Pogliani, and Nilton Lincopan
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Enterobacterales ,ESBL ,Dairy cattle ,Antimicrobial resistance ,Genomic surveillance ,Brazil ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: Extended-spectrum β-lactamase (ESBL)–producing Enterobacter cloacae complex (ECC) members have been a leading cause of severe infections in hospital setting and have lately been recognized as important pathogens for animals. In this article, we report phylogenomic data of a multidrug-resistant and CTX-M-15–positive E. hormaechei belonging to ST78 isolated from a calf with omphalitis. Methods: Genomic DNA was extracted and sequenced using the Illumina NextSeq platform. De novo assembly was performed by Unicycler and in silico prediction accomplished by curated bioinformatics tools. Single nucleotide polymorphism (SNP)-based comparative phylogenomic analysis was conducted by using publicly available ECC genomes belonging to ST78. Results: The genome size was calculated at 3 8465 40 bp, comprising 4717 total genes, 3 rRNAs, 43 tRNAs, 7 ncRNAs, and 74 pseudogenes. The animal-associated E. hormaechei (ECBEZ strain) ST78 harboured the blaCTX-M-15 ESBL gene in addition to other critically important resistance genes conferring resistance to β-lactams, aminoglycosides, fosfomycin, phenicol, quinolones, sulphonamides, tetracyclines, and trimethoprim. Phylogenetic analysis revealed that ECBEZ is closely related to human-isolated strains from Asian and African countries. Conclusion: Phylogenomic analysis of CTX-M-15-producing E. hormaechei from animal infection reveals that ST78 is a successful One Health clone among ECC members. Furthermore, data presented in this study reinforce the urgent need to monitor ESBL-producing ECC members in veterinary settings. more...
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- 2022
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30. Isolation and characterisation of colistin-resistant Enterobacterales from chickens in Southeast Nigeria
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M.U. Anyanwu, R. Marrollo, M. Paolucci, F. Brovarone, P. Nardini, K.F. Chah, S.V.O. Shoyinka, and E. Carretto
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Antimicrobial resistance ,Enterobacterales ,Nigeria ,mcr-1 ,Mobile colistin resistance ,mcr-1.22 ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: Resistance to colistin (CST) mediated by mobile genetic elements has had a broad impact worldwide. There is an intensified call for epidemiological surveillance of mcr in different reservoirs to preserve CST for future generations. In Nigeria, the poultry industry is a key livestock sector. This study was undertaken to screen putative colistin-resistant Enterobacterales (CST-r-E) from poultry birds in Southeast Nigeria and to determine the genetic relatedness of mcr-harbouring isolates. Methods: Faecal and cloacal swab samples (n = 785) were collected from chickens in 17 farms located in three contiguous states in Southeast Nigeria between March–November 2018. Following selective culture, CST-r-E were isolated. Confirmation of CST resistance, antimicrobial susceptibility testing, molecular detection of genes mcr-1 to mcr-10, multilocus sequence typing (MLST) and randomly amplified polymorphic DNA (RAPD) analysis were performed on the isolates. A questionnaire was distributed to investigate the knowledge about CST and its use of chicken farm caretakers. Results: Of the 785 samples evaluated, 45 (5.7%) were positive for 48 CST-r-E, among which 23 harboured the mcr-1 gene (22 Escherichia coli and 1 Klebsiella pneumoniae). In two E.coli isolates, a new allelic variant (mcr-1.22) was detected. RAPD analysis allowed the identification of 11 different fingerprints. MLST also revealed 11 STs, with 3 of them being novel. Conclusion: mcr has significantly spread in poultry birds of Southeast Nigeria, which poses a worrisome risk to veterinary and human health. Strategies to prevent indiscriminate use of CST in farms should be quickly adopted before CST resistance becomes a huge global health issue. more...
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- 2021
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31. Clinical and epidemiological features of patients colonised by different types of carbapenemase-producing Enterobacterales
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Roy Assis, Michal Lasnoy, and Amos Adler
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Carbapenemase ,Enterobacterales ,CPE ,Colonisation ,Hospital-acquired infection ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: The aim of this study was to compare the epidemiological and clinical characteristics of hospitalised patients colonised or infected by different types of carbapenemase-producing Enterobacterales (CPE) and to analyse the differences in their outcome. Methods: This was a retrospective comparative study of all patients colonised or infected by KPC-, NDM- or OXA-48-producing CPE who were hospitalised between 1 January 2018 and 30 June 2019. Microbiological, demographic and clinical data were collected from the patients’ computerised files. Results: One type of CPE was isolated in 285 patients, including 138 with KPC-CPE, 94 with NDM-CPE and 53 with OXA-48-CPE. The most common CPE types were KPC-Klebsiella pneumoniae (n = 47), OXA-48-Escherichia coli (n = 38), NDM-Enterobacter cloacae complex (n = 35) and KPC-Citrobacter freundii (n = 37). All three groups of patients were similar with respect to their risk factors, with the exception of previous exposure to antimicrobials that was more common in patients with KPC-CPE compared with OXA-48-CPE. Also, these patients were more likely to be co-infected by other multidrug-resistant bacteria. Clinical infections were more common in KPC-CPE than in OXA-48-CPE carriers (9.9% vs. 1.9%; P = 0.033). No other demographic or clinical variables were found to be correlated with clinical infections. Conclusion: Our study suggests that colonisation by OXA-48-CPE might be less risky compared with KPC-CPE. more...
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- 2021
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32. Genetic characteristics of OXA-48-producing Enterobacterales from China
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Lifeng Wang, Ling Guo, Kun Ye, and Jiyong Yang
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Genomics ,Enterobacterales ,Klebsiella pneumoniae ,Carbapenemase ,OXA-48 ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: In China, OXA-48-producing Enterobacterales have been identified sporadically, causing small-scale regional outbreaks. This study investigated the molecular epidemiology, transmission and evolution of OXA-48-producing Enterobacterales and pOXA48 from mainland China. Methods: We conducted a multicentre resistance monitoring project from 2013–2018. Genome sequencing of OXA-48-produicng isolates was performed. SNPs were analysed. Eleven isolates were selected for subsequent SMRT sequencing. Genome sequences were annotated, and alignment of the complete sequences of blaOXA-48-carrying plasmids from a subset of isolates that underwent long-read sequencing was performed. Results: In total, 41 OXA-48-producing Enterobacterales were included in this study (34 Klebsiella pneumoniae, 3 Escherichia coli, 3 Enterobacter cloacae complex and 1 Klebsiella oxytoca). OXA-48-produicng K. pneumoniae (OXAKp) ST383, ST147 and ST11 caused outbreaks of different scales in our hospital. OXA-48-producing E. coli ST156 and ST648, E. cloacae complex ST414 and ST418, and K. oxytoca ST34 were also identified. blaOXA-48 was embedded in a Tn1999.2 structure located in IncL plasmids with different sizes (63.58–109.14 kb). Importantly, K. pneumoniae ST11 co-producing KPC-2 and OXA-48 was identified in our hospital and it is possible that KPC-2-producing K. pneumoniae ST11 obtained the blaOXA-48-carrying plasmid during its spread. A novel 109-kb blaOXA-48-carrying IncL plasmid was identified from OXAKp ST11. Possibly, two plasmids in OXAKp ST383 were integrated to form this larger plasmid. Conclusion: OXA-48-produicng Enterobacterales were sporadic in China. Importantly, K. pneumoniae ST11 co-producing KPC-2 and OXA-48 has emerged causing an outbreak in China. This high-risk multidrug-resistant clone exhibited high compatibility and strong integration ability with foreign resistance plasmids. more...
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- 2021
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33. Genomic data reveals the emergence of an IncQ1 small plasmid carrying blaKPC-2 in Escherichia coli of the pandemic sequence type 648
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Bruna Fuga, Louise Cerdeira, Quézia Moura, Herrison Fontana, Danny Fuentes-Castillo, Albalúcia C. Carvalho, and Nilton Lincopan
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Enterobacterales ,Carbapenemase ,KPC-2 ,Plasmidome ,Resistome ,Phylogenomics ,Microbiology ,QR1-502 - Abstract
Objectives: The global success of carbapenem-resistant pathogens has been attributed to large plasmids carrying blaKPC genes circulating among high-risk clones. In this study, we sequenced the genome of a carbapenem-resistant Escherichia coli strain (Ec351) isolated from a human infection. Phylogenomic analysis based on single nucleotide polymorphisms (SNPs) as well as the comparative resistome and plasmidome of globally disseminated blaKPC-2-positive E. coli strains with identical sequence type (ST) were further investigated. Methods: Total DNA was sequenced using an Illumina NextSeq 500 platform and was assembled using Unicycler. Genomic data were evaluated through bioinformatics tools available from the Center of Genomic Epidemiology and by in silico analysis. Results: Genomic analysis revealed the convergence of a wide resistome and virulome in E. coli ST648, showing a high-level phylogenetic relationship with a KPC-2-positive ST648 cluster identified in the USA and association with international clade 2. Additionally, the emergence of an IncQ1 small plasmid (pEc351) carrying blaKPC-2 (on an NTEKPC-IId element), aph(3')-VIa, and plasmid regulatory and replication genes in the pandemic clone ST648 is reported. Conclusion: Identification of a blaKPC-2-positive IncQ1 plasmid in a high-risk E. coli clone represents rapid adaptation and expansion of these small plasmids encoding carbapenemases to novel bacterial hosts with global distribution, which deserves continued monitoring. more...
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- 2021
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34. Third-generation cephalosporin resistance in clinical isolates of Enterobacterales collected between 2016–2018 from USA and Europe: genotypic analysis of β-lactamases and comparative in vitro activity of cefepime/enmetazobactam
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Adam Belley, Ian Morrissey, Stephen Hawser, Nimmi Kothari, and Philipp Knechtle
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Enmetazobactam ,Tazobactam ,Enterobacterales ,Cephalosporin ,ESBL ,β-Lactam ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: This study aimed to investigate third-generation cephalosporin (3GC) resistance determinants [extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases and OXA-type β-lactamases] in contemporary clinical Enterobacterales isolates and to determine the in vitro activity of β-lactams and β-lactam/β-lactamase inhibitor combinations, including the investigational combination of cefepime and the novel β-lactamase inhibitor enmetazobactam. Methods: Antibacterial susceptibility of 7168 clinical Enterobacterales isolates obtained between 2016–2018 from North America and Europe was determined according to CLSI guidelines. Phenotypic resistance to the 3GC ceftazidime (MIC ≥ 16 µg/mL) and/or ceftriaxone (MIC ≥ 4 µg/mL) but retaining susceptibility to meropenem (MIC ≤ 1 µg/mL) was determined. β-Lactamase genotyping was performed on clinical isolates with ceftazidime, ceftriaxone, cefepime or meropenem MIC ≥ 1 µg/mL. Results: Phenotypic resistance to 3GCs occurred in 17.5% of tested isolates, whereas 2.1% of isolates were resistant to the carbapenem meropenem. Within the 3GC-resistant subgroup, 60.1% (n = 752) of isolates encoded an ESBL, 25.6% (n = 321) encoded an AmpC-type β-lactamase and 0.9% (n = 11) encoded an OXA-type β-lactamase. Susceptibility of the subgroup to piperacillin/tazobactam (57.5%) and ceftolozane/tazobactam (71.3%) was more...
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- 2021
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35. Resistance to ceftazidime/avibactam in infections and colonisations by KPC-producing Enterobacterales: a systematic review of observational clinical studies
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Stefano Di Bella, Daniele Roberto Giacobbe, Alberto Enrico Maraolo, Valentina Viaggi, Roberto Luzzati, Matteo Bassetti, Francesco Luzzaro, and Luigi Principe
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Ceftazidime/avibactam ,KPC ,Enterobacterales ,Antimicrobial resistance ,Last-resort antibiotics ,Antimicrobial stewardship ,Microbiology ,QR1-502 - Abstract
ABSTRACT: Objectives: Ceftazidime/avibactam (CAZ-AVI), approved in 2015, is an important first-line option for Klebsiella pneumoniae carbapenemase-producing Enterobacterales (KPC-E). Although still uncommon, resistance to CAZ-AVI has emerged and may represent a serious cause of concern. Methods: We performed a systematic literature review of clinical and microbiological features of infections and colonisations by CAZ-AVI-resistant KPC-E, focused on the in vivo emergence of CAZ-AVI resistance in different clinical scenarios. Results: Twenty-three papers were retrieved accounting for 42 patients and 57 isolates, mostly belonging to K. pneumoniae ST258 harbouring D179Y substitution in the KPC enzyme. The USA, Greece and Italy accounted for 80% of cases. In one-third of isolates resistance was not associated with previous CAZ-AVI exposure. Moreover, 20% of the strains were colistin-resistant and 80% were extended-spectrum β-lactamase (ESBL)-producers. The majority of infected patients had severe underlying diseases (39% cancer, 22% solid-organ transplantation) and 37% died. The abdomen, lung and blood were the most involved infection sites. Infections by CAZ-AVI-resistant strains were mainly treated with combination therapy (85% of cases), with meropenem being the most common (65%) followed by tigecycline (30%), gentamicin (25%), colistin (25%) and fosfomycin (10%). Despite the emergence of resistance, 35% of patients received CAZ-AVI. Conclusion: Taken together, these data highlight the need for prompt susceptibility testing including CAZ-AVI for Enterobacterales, at least in critical areas. Resistance to CAZ-AVI is an urgent issue to monitor in order to improve both empirical and targeted CAZ-AVI use as well as the management of patients with infections caused by CAZ-AVI-resistant strains. more...
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- 2021
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36. Molecular characterization of clinical isolates of Enterobacterales with elevated MIC values for aztreonam-avibactam from the INFORM global surveillance study, 2012–2017
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Mark Estabrook, Krystyna M. Kazmierczak, Mark Wise, Francis F. Arhin, Gregory G. Stone, and Daniel F. Sahm
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Aztreonam-avibactam ,Surveillance ,Enterobacterales ,Resistance ,PBP3 ,Microbiology ,QR1-502 - Abstract
Objectives: While aztreonam-avibactam is a potent β-lactam-β-lactamase-inhibitor combination, reduced in vitro activity against some Enterobacterales isolates has been reported. In this study, globally collected clinical isolates of Enterobacterales with elevated minimum inhibitory concentrations (MICs) for aztreonam-avibactam were examined for potential resistance mechanisms. Methods: Isolates with aztreonam-avibactam MICs ≥8 μg/mL (n = 55: Escherichia coli, n = 38; Enterobacter cloacae, n = 10; Klebsiella pneumoniae, n = 3; others, n = 4) and more...
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- 2021
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37. Gold standard susceptibility testing of fosfomycin in Staphylococcus aureus and Enterobacterales using a new agar dilution panel®
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Floriana Campanile, Mandy Wootton, Leanne Davies, Ausilia Aprile, Alessia Mirabile, Stefano Pomponio, Federica Demetrio, Dafne Bongiorno, Timothy R. Walsh, Stefania Stefani, and Maria Lina Mezzatesta
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Staphylococcus aureus ,Enterobacterales ,Fosfomycin ,Agar dilution ,Commercial AD panel ,Microbiology ,QR1-502 - Abstract
Objectives: Many clinical laboratories have difficulty in routinely performing in vitro fosfomycin susceptibility testing using the agar dilution (AD) method, considered to be the gold standard method. The objective of our work was to evaluate a rapid commercial fosfomycin agar dilution panel against clinical Staphylococcus aureus and Enterobacterales strains, in two different centres located in Italy and in the UK. Methods: A total of 99 Enterobacterales (mostly Escherichia coli and Klebsiella pneumoniae) and 80 S. aureus clinical isolates was used to evaluate the commercial device, a 12-well panel containing fosfomycin incorporated into CA-MH agar supplemented with 25 mg/L of glucose-6-phosphate (Liofilchem S.r.l., Roseto degli Abruzzi, Italy). Testing was performed in two centres (Italy and UK) and kit results were compared against the gold standard in-house AD MIC method. Results: According to the EUCAST breakpoints, fosfomycin inhibited 61% of the S. aureus strains, and 76% of the Enterobacterales isolates tested by the AD reference method. There was a Categorical Agreement (CA) of 100% and an Essential Agreement (EA) of 91.25% for S. aureus; while the Enterobacterales strains showed a CA of 94% and an EA of 97%. No evaluation errors were observed among S. aureus, while 5% Major Error and 1% Very Major Error were observed for the Enterobacterales. Conclusions: Our results confirmed the feasibility of determining fosfomycin susceptibility using a commercial AD panel as a routine substitution for the AD test. The few differences observed were only in strains with MICs around the breakpoint used. more...
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- 2020
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38. Association of blaNDM-1 with blaKPC-2 and aminoglycoside-modifying enzyme genes among Klebsiella pneumoniae, Proteus mirabilis and Serratia marcescens clinical isolates in Brazil
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Elza Ferreira Firmo, Elizabeth Maria Bispo Beltrão, Felipe Rogério Ferreira da Silva, Luis Carlos Alves, Fábio André Brayner, Dyana Leal Veras, and Ana Catarina Souza Lopes
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Enterobacterales ,NDM ,KPC ,Aminoglycoside-modifying enzyme ,Microbiology ,QR1-502 - Abstract
Objectives: Carbapenemase-producing Enterobacterales are frequently involved in healthcare-associated infections worldwide. The objectives of this study were to investigate (i) the frequency of the main genes encoding carbapenemases, 16S rRNA methylases and aminoglycoside-modifying enzymes (AMEs) as well as the mcr gene and (ii) the clonal relationship of enterobacteria isolates resistant to carbapenems and aminoglycosides from colonisation and infection in patients from hospitals in northeastern Brazil. Methods: Antimicrobial susceptibility was determined using an automated VITEK®2 system. Presence of carbapenemase, AME and 16S rRNA methylase genes as well as the mcr gene was determined by PCR and amplicon sequencing. Genetic variability was determined by ERIC-PCR. Results: A total of 35 isolates resistant to carbapenems and aminoglycosides were selected for this study. Klebsiella pneumoniae was most common (45.7%), followed by Proteus mirabilis (28.6%) and Serratia marcescens (25.7%). AME genes were found in 97.1% of isolates, most commonly aph(3ʹ)-VI and aac(6')-Ib. The blaNDM-1 and blaKPC-2 genes were detected in 25.7% and 88.6% of isolates, respectively; five isolates harboured these genes concomitantly. According to the literature, this is the first report of the association of blaNDM-1 and blaKPC-2 in P. mirabilis and S. marcescens in Brazil. The isolates showed a multiclonal profile by ERIC-PCR. Conclusion: The emergence of blaNDM-1 associated with blaKPC-2 and AME genes in K. pneumoniae, P. mirabilis and S. marcescens isolates with a multiclonal profile is of concern as this limits therapeutic options. These results should alert medical authorities to establish rigorous detection methods to reduce the spread of these antimicrobial resistance genes. more...
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- 2020
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39. Performance of disk diffusion and broth microdilution for fosfomycin susceptibility testing of multidrug-resistant clinical isolates of Enterobacterales and Pseudomonas aeruginosa
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María Fernanda Mojica, Elsa De La Cadena, Cristhian Hernández-Gómez, Adriana Correa, Tobias Manuel Appel, Christian José Pallares, and María Virginia Villegas
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Fosfomycin ,Antimicrobial activity ,Enterobacterales ,Pseudomonas aeruginosa ,Susceptibility tests ,Microbiology ,QR1-502 - Abstract
Objectives: This study aimed to evaluate the susceptibility of clinical isolates of Enterobacterales and Pseudomonas aeruginosa to fosfomycin and to determine the concordance of disk diffusion (DD) and broth microdilution (BMD) with agar dilution (AD) for fosfomycin susceptibility testing. Methods: The activity of fosfomycin against 225 clinical isolates of Escherichia coli (n = 64), Klebsiella pneumoniae (n = 68), Enterobacter spp. (n = 28) and P. aeruginosa (n = 65) was tested by AD, DD and BMD. For DD, results were recorded considering and not considering colonies growing within the inhibition halo as recommended by the CLSI and EUCAST, respectively. Escherichia coli breakpoints were used for all Enterobacterales. Results were reported as categorical agreement (CA), major error (ME; false-resistant), very major error (VME; false-susceptible) and minor error (any other discrepancies). Results: Fosfomycin susceptibility of all tested species was >90% by AD. Following CLSI guidelines, DD was the only method reaching ≥90% CA with AD for E. coli and K. pneumoniae, albeit yielding 6% ME. Neither DD nor BMD achieved acceptable CA percentages for Enterobacter spp. Following EUCAST guidelines, none of the methods had CA ≥ 90%. For Enterobacterales, the best performance of DD is achieved when read as indicated by EUCAST but interpreted according the CLSI breakpoints (>97% CA; 0% VME; ≤2% ME). For P. aeruginosa, BMD yielded the best results (89% CA; 0% VME; 11% ME). Conclusion: Neither DD or BMD provide accurate results owing to unacceptable ME and VME percentages even when performed as intended by the guidelines. more...
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- 2020
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40. Evaluation of the activity of cefepime/enmetazobactam against Enterobacterales bacteria collected in Europe from 2019 to 2021, including third-generation cephalosporin-resistant isolates.
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Morrissey I, Hawser S, Kothari N, Dunkel N, Quevedo J, Belley A, Henriksen AS, and Attwood M
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- Humans, Europe, beta-Lactamases metabolism, Azabicyclo Compounds pharmacology, beta-Lactamase Inhibitors pharmacology, Ceftazidime pharmacology, Piperacillin, Tazobactam Drug Combination pharmacology, Cephalosporins pharmacology, Meropenem pharmacology, Drug Combinations, Triazoles, Cefepime pharmacology, Anti-Bacterial Agents pharmacology, Microbial Sensitivity Tests, Enterobacteriaceae drug effects, Enterobacteriaceae isolation & purification, Enterobacteriaceae Infections microbiology
- Abstract
Objectives: This study was performed to investigate the activity of the novel ß-lactam/ß-lactamase inhibitor combination cefepime/enmetazobactam, against recently circulating Enterobacterales isolates from Europe from 2019 to 2021., Methods: A total of 2627 isolates were collected, and antimicrobial susceptibility was determined according to the European Committee on Antimicrobial Susceptibility Testing guidelines. Isolates with phenotypic resistance to ceftriaxone and ceftazidime (but susceptible to meropenem) and isolates nonsusceptible to meropenem were screened for the presence of ß-lactamases., Results: Overall, susceptibility to third-generation cephalosporins was 77%, and 97.3% were susceptible to meropenem. Cefepime/enmetazobactam susceptibility was 97.9% (72% of these isolates were Klebsiella pneumoniae from Italy), compared with 80.0% susceptibility to piperacillin/tazobactam and 99.4% to ceftazidime/avibactam. A total of 320 isolates (12.2%) were resistant to third-generation cephalosporins but susceptible to meropenem, and virtually all (96.3%) carried an extended-spectrum ß-lactamase with or without an AmpC and these were all susceptible to cefepime/enmetazobactam. Most meropenem-nonsusceptible isolates carried a KPC (68%), which were not inhibited by cefepime/enmetazobactam but were inhibited by ceftazidime/avibactam. Additionally, most meropenem-nonsusceptible isolates carrying OXA-48 (9/12 isolates) were susceptible to cefepime/enmetazobactam., Conclusions: Cefepime/enmetazobactam was highly active against Enterobacterales isolates, especially those resistant to third-generation cephalosporins. These data suggest that cefepime/enmetazobactam could be used as a carbapenem-sparing agent to replace piperacillin/tazobactam., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...
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- 2024
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41. Genomic analysis of multidrug-resistant CTX-M-15-positive Klebsiella pneumoniae belonging to the highly successful ST15 clone isolated from a dog with chronic otitis
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Fábio P. Sellera, Ralf Lopes, Daniel F.M. Monte, Brenda Cardoso, Fernanda Esposito, Carolina dos Anjos, Luciano C.B.A. da Silva, and Nilton Lincopan
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Enterobacterales ,ESBL ,K24 ,KL24 ,Companion animal ,One health ,Microbiology ,QR1-502 - Abstract
Background: Extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae have been increasingly reported worldwide as a frequent cause of human and animal infections. K. pneumoniae belonging to the K24 capsular serotype and sequence type (ST) ST15 has been considered a global successful clone responsible for the spread of the blaCTX-M-15 gene. Objective: To report the draft genome sequence of a multidrug-resistant CTX-M-15-positive K. pneumoniae K24-ST15 strain (L3KP1), which was isolated from a dog with chronic otitis. Methods: Genomic DNA was extracted and sequenced using Illumina NextSeq platform. De novo assembly was performed by SPAdes and in silico prediction accomplished by curated bioinformatics tools. Results: The genome size was calculated at 5 642 348 bp, with a GC content of 57.11%, and comprising 5601 total genes, 52 tRNAs, 8 rRNAs, 9 ncRNAs and 105 pseudogenes. The K. pneumoniae L3KP1 strain belonged to ST15 and carried the yersiniabactin biosynthetic gene cluster [ybt 10 (YbST28) in the integrative conjugative element ICEKp4], and the KL24 locus encoding capsular serotype K24. Besides the blaCTX-M-15 ESBL gene, other clinically important resistance genes to β-lactams, aminoglycosides, fosfomycin, macrolides, phenicol, quinolones, sulfonamides, tetracyclines and trimethoprim were detected. Additionally, heavy metals and disinfectant resistance genes were also identified. Conclusion: This draft genome might be useful for comparative genomic analyses of the international clone of K. pneumoniae K24-ST15-CTX-M-15. In addition, information presented in this study also shed light on the urgent need to monitor ESBL-producing K. pneumoniae in veterinary hospitals. more...
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- 2020
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42. Global trends in carbapenem- and difficult-to-treat-resistance among World Health Organization priority bacterial pathogens: ATLAS surveillance program 2018-2022.
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Wise MG, Karlowsky JA, Mohamed N, Hermsen ED, Kamat S, Townsend A, Brink A, Soriano A, Paterson DL, Moore LSP, and Sahm DF
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- Humans, World Health Organization, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa genetics, Pseudomonas aeruginosa isolation & purification, Acinetobacter baumannii drug effects, Acinetobacter baumannii genetics, Acinetobacter baumannii isolation & purification, beta-Lactamases genetics, Global Health, Epidemiological Monitoring, Gram-Negative Bacterial Infections microbiology, Gram-Negative Bacterial Infections epidemiology, Drug Resistance, Multiple, Bacterial, Gram-Negative Bacteria drug effects, Gram-Negative Bacteria isolation & purification, Gram-Negative Bacteria genetics, Gram-Negative Bacteria classification, Enterobacteriaceae drug effects, Enterobacteriaceae genetics, Enterobacteriaceae isolation & purification, Carbapenems pharmacology, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology
- Abstract
Objectives: To report trends in carbapenem resistance and difficult-to-treat resistance (DTR) among clinical isolates of Gram-negative priority pathogens collected by the ATLAS global surveillance program from 2018 to 2022., Methods: Reference broth microdilution testing was performed in a central laboratory for 79,214 Enterobacterales, 30,504 Pseudomonas aeruginosa, and 13,500 Acinetobacter baumannii-calcoaceticus complex isolates collected by a constant set of 157 medical centres in 49 countries in Asia Pacific (APAC), Europe (EUR), Latin America (LATAM), Middle East-Africa (MEA), and North America (NA) regions. MICs were interpreted by 2023 CLSI M100 breakpoints. β-lactamase genes were identified for meropenem-nonsusceptible (MIC ≥2 mg/L) Enterobacterales isolates., Results: Carbapenem-resistant Enterobacterales (CRE) detection increased (P < 0.05) in APAC, EUR, LATAM, and MEA regions and decreased in NA, while annual DTR percentages increased in all five regions. Carbapenem-resistant P. aeruginosa (CRPA; decreased in MEA region) and carbapenem-resistant A. baumannii-calcoaceticus complex (CRAB; decreased in MEA region and increased in EUR) remained relatively stable over time in all regions, although notably, annual percentages of CRAB and DTR A. baumannii-calcoaceticus complex isolates were consistently >25 percentage points lower in NA than in other regions. For all regions except NA, the majority of changes in CRE percentages could be attributed to hospital-acquired infections. Among meropenem-nonsusceptible Enterobacterales, KPC was the most frequent carbapenemase in NA and EUR each year. NDM was the most prevalent carbapenemase detected in 2022 in other global regions., Conclusion: CRE, CRPA, CRAB, and DTR rates vary among global regions over time highlighting the need for continuing surveillance to inform treatment strategies and antimicrobial stewardship., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...
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- 2024
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43. Hybrid genome assembly of colistin-resistant mcr-1.5-producing Escherichia coli ST354 reveals phylogenomic pattern associated with urinary tract infections in Brazil.
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Fuga B, Sellera FP, Esposito F, Moura Q, Pillonetto M, and Lincopan N
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- Brazil, Humans, Microbial Sensitivity Tests, Plasmids genetics, Genomics, Whole Genome Sequencing, Urinary Tract Infections microbiology, Colistin pharmacology, Phylogeny, Escherichia coli genetics, Escherichia coli drug effects, Escherichia coli Proteins genetics, Escherichia coli Infections microbiology, Genome, Bacterial, Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial genetics
- Abstract
Background: The rapid and global spread of Escherichia coli carrying mcr-type genes at the human-animal-environmental interface has become a serious global public health problem., Objective: To perform a genomic investigation of a colistin-resistant E. coli strain (14005RM) causing urinary tract infection, using a hybrid de novo assembly of Illumina/Nanopore sequence data, presenting phylogenomic insights into the relationship with mcr-1-positive strains circulating at the human-animal-environmental interface, in Brazil., Methods: Genomic DNA was sequenced using both the Illumina NexSeq and Nanopore MinION platforms. De novo hybrid assembly was performed by Unicycler. Genomic data were assessed by in silico prediction and bioinformatic tools., Results: The genome assembly size was 5 333 039 bp. The mcr-1.5-positive E. coli strain 14005RM belongs to the sequence type ST354 and presented a broad resistome (antibiotics, heavy metals, disinfectants, and glyphosate) and virulome. The mcr-1.5 gene was carried by an IncI2 plasmid (p14005RM, sizing 65,458 kb). Full genome SNP-based phylogenetic analysis reveals that mcr-1.5-producing E. coli strain 14005RM is highly related (> 98% identity) to colistin-resistant mcr-1.1-positive ST354 lineages associated with urinary tract infections in Brazil since 2015., Conclusion: Mobile colistin resistance within the Brazilian One Health microbiosphere is mediated by mcr gene variants propagated by IncX4, IncHI2, and IncI2 plasmids, circulating among global clones of E. coli., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...
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- 2024
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44. Genomic scan of a healthcare-associated NDM-1-producing Citrobacter freundii ST18 isolated from a green sea turtle impacted by plastic pollution.
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Aravena-Ramírez V, Fuentes-Castillo D, Vilaça ST, Goldberg DW, Esposito F, Silva-Pereira TT, Fontana H, Sellera FP, and Lincopan N
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- Animals, Humans, Citrobacter freundii genetics, Anti-Bacterial Agents pharmacology, Genomics, Repressor Proteins, Turtles, Cross Infection
- Abstract
Background: Carbapenemase-producing Citrobacter freundii has been reported as a leading cause of healthcare-associated infections. Particularly, C. freundii belonging to the sequence type (ST) 18 is considered to be an emerging nosocomial clone., Objectives: To report the genomic background and phylogenomic analysis of a multidrug-resistant NDM-1-producing C. freundii ST18 (strain CF135931) isolated from an endangered green sea turtle affected by plastic pollution in Brazil., Methods: Genomic DNA was extracted and sequenced using the Illumina NextSeq platform. De novo assembly was performed by CLC Workbench, and in silico analysis accomplished by bioinformatics tools. For phylogenomic analysis, publicly available C. freundii (txid:546) genome assemblies were retrieved from the NCBI database., Results: The genome size was calculated at 5 290 351 bp, comprising 5263 total genes, 4 rRNAs, 77 tRNAs, 11ncRNAs, and 176 pseudogenes. The strain belonged to C. freundii ST18, whereas resistome analysis predicted genes encoding resistance to β-lactams (bla
NDM-1 , blaOXA-1 , blaCMY-117 , and blaTEM-1C ), aminoglycosides (aph(3'')-Ib, aadA16, aph(3')-VI, aac(6')-Ib-cr, and aph(6)-Id), quinolones (aac(6')-Ib-cr), macrolides (mph(A) and erm(B)), sulphonamides (sul1 and sul2), tetracyclines (tetA and tetD), and trimethoprim (dfrA27). The phylogenomic analysis revealed that CF135931 strain is closely related to international human-associated ST18 clones producing NDM-1., Conclusion: Genomic surveillance efforts are necessary for robust monitoring of the emergence of drug-resistant strains and WHO critical priority pathogens within a One Health framework. In this regard, this draft genome and associated data can improve understanding of dissemination dynamics of nosocomial clones of carbapenemase-producing C. freundii beyond hospital walls. In fact, the emergence of NDM-1-producing C. freundii of global ST18 in wildlife deserves considerable attention., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...- Published
- 2024
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45. In vitro activity of aztreonam-avibactam and comparators against Metallo-β-Lactamase-producing Enterobacterales from ATLAS Global Surveillance Program, 2016-2020.
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Rossolini GM, Arhin FF, and Kantecki M
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- Aztreonam pharmacology, beta-Lactamases genetics, Azabicyclo Compounds pharmacology, Ascomycota, Gammaproteobacteria, Anti-Infective Agents
- Abstract
Objectives: Metallo-β-lactamase (MBL)-producing Enterobacterales are a major challenge worldwide due to limited treatment options. Aztreonam-avibactam (ATM-AVI), which is under clinical development, has shown activity against MBL-positive isolates. This study evaluated the prevalence of MBL producers and the nature of enzymes among a global collection of clinical isolates of Enterobacterales from the Antimicrobial Testing Leadership and Surveillance program (ATLAS) surveillance program (2016-2020), and the antimicrobial activity of ATM-AVI and comparators against this collection., Methods: Non-duplicate clinical isolates of Enterobacterales (N = 106 686) collected across 63 countries were analysed. Antimicrobial susceptibility was performed using broth microdilution. Minimum inhibitory concentrations (MICs) were interpreted using Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing breakpoints. Provisional pharmacokinetic/pharmacodynamic breakpoint of ≤8 mg/L was considered for ATM-AVI. β-lactamase genes were characterized by polymerase chain reaction and sequencing. The Cochran Armitage Trend test was used to determine significant trends in percentage of isolates over time., Results: Overall, MBL-positive isolates were 1.6% of total Enterobacterales isolates globally, with a significant increasing trend observed over time, globally and across regions (P < 0.05). New Delhi MBL (NDM) was the most common MBL (83.3%). ATM-AVI demonstrated potent activity against MBL-positive isolates (MIC ≤8 mg/L: 99.4% isolates inhibited; MIC
90 , 1 mg/L). Consistent activity was also noted across different regions. Potent activity was demonstrated against different NDM variants and MBL-positive isolates co-carrying other carbapenemases (98.1% and 99.7% isolates inhibited at ≤8 mg/L, respectively). About 0.6% MBL-positive isolates (10/1707) had MICs >8 mg/L for ATM-AVI., Conclusion: ATM-AVI demonstrated potent activity against MBL-positive isolates, including NDM variants and MBL-positive isolates co-carrying other carbapenemases, and may represent a good option for treating infections caused by MBL-positive Enterobacterales., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...- Published
- 2024
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46. Genomic data of global clones of CTX-M-65-producing Escherichia coli ST10 from South American llamas inhabiting the Andean Highlands of Peru.
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Cardenas-Arias AR, Sano E, Cardoso B, Fuga B, Sellera FP, Esposito F, Aravena-Ramírez V, Huaman DC, Gonzales CD, Espinoza LL, Hernández LM, and Lincopan N
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- Animals, Humans, Escherichia coli genetics, Peru, Anti-Bacterial Agents pharmacology, beta-Lactamases genetics, Genomics, Camelids, New World, Escherichia coli Infections epidemiology, Escherichia coli Infections veterinary
- Abstract
Background: The global spread of extended-spectrum β-lactamase (ESβL)-producing Escherichia coli has been considered a One Health issue that demands continuous genomic epidemiology surveillance in humans and non-human hosts., Objectives: To report the occurrence and genomic data of ESβL-producing E. coli strains isolated from South American llamas inhabiting a protected area with public access in the Andean Highlands of Peru., Methods: Two ESβL-producing E. coli strains (E. coli L1LB and L2BHI) were identified by MALDI-TOF. Genomic DNAs were extracted and sequenced using the Illumina NextSeq platform. De novo assembly was performed by CLC Genomic Workbench and in silico prediction was accomplished by curated bioinformatics tools. SNP-based phylogenomic analysis was performed using publicly available genomes of global E. coli ST10., Results: Escherichia coli L1LB generated a total of 4 000 11 and L2BHI a total of 4 002 54 paired-end reads of ca.164 × and ca. 157 ×, respectively. Both E. coli strains were assigned to serotype O8:H4, fimH41, and ST10. The bla
CTX-M-65 ESβL gene, along with other medically important antimicrobial resistance genes, was predicted. Broad virulomes, including the presence of the astA gene, were confirmed. The phylogenomic analysis revealed that E. coli L1LB and L2BHI strains are closely related to isolates from companion animals and human hosts, as well as environmental strains, previously reported in North America, South America, Africa, and Asia., Conclusion: Presence of ESβL-producing E. coli ST10 in South American camelids with historical and cultural importance supports successful expansion of international clones of priority pathogens in natural areas with public access., (Copyright © 2023. Published by Elsevier Ltd.) more...- Published
- 2024
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47. In vitro activity of ceftazidime-avibactam against Gram-negative strains in Chile 2015-2021.
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Torres-Castillo LC, Fandiño C, Ramos MP, Ramos-Castaneda JA, Rioseco ML, and Juliet C
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- Humans, Chile, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Carbapenems, Pseudomonas aeruginosa, Ceftazidime pharmacology, Ceftazidime therapeutic use, Amikacin pharmacology
- Abstract
Objectives: Ceftazidime-avibactam (CAZ-AVI) combines ceftazidime and a reversible β-lactamase inhibitor that has shown activity against multidrug-resistant (MDR) Enterobacterales and P. aeruginosa. Using data from the Antimicrobial Testing Leadership and Surveillance program (ATLAS), this study examined the in vitro antimicrobial activity of CAZ-AVI and other antibiotics against Gram-negative bacteria collected from Chilean hospitals between 2015 and 2021., Methods: Clinical isolates of Enterobacterales and P. aeruginosa were collected from three medical centres in Chile. Blood, abdominal fluid, urine, soft tissues, and respiratory tract samples were obtained from infected patients. Minimum inhibitory concentrations using the broth microdilution method were determined for susceptibility testing, and the Clinical and Laboratory Standards Institute (CLSI) breakpoints were used for interpreting the results. Extended-spectrum β-lactamases (ESBL) and carbapenemase genes were also detected through polymerase chain reaction., Results: A total of 2600 Enterobacterales and 836 P. aeruginosa were analysed. CAZ-AVI was the antibiotic with the highest in vitro activity against Enterobacterales (99.72%). The incidence of carbapenem-resistant Enterobacterales (CRE) was 1.5% (n = 39), and the antibiotics with the best in vitro activity were tigecycline (92.31%), CAZ-AVI (88.57%), and amikacin (79.49%). CAZ-AVI was the antibiotic with the best activity against ESBL-producing Enterobacterales (99.34%) and MDR Enterobacterales (99.31%). For KPC-producing Enterobacterales, susceptibility to amikacin was 100%, whereas susceptibility to CAZ-AVI was 91.67%. Regarding MDR and difficult-to-treat resistance P. aeruginosa, 44.83% and 38.99% were susceptible to CAZ-AVI, respectively., Conclusion: CAZ-AVI shows excellent in vitro activity against Enterobacterales in general, CRE, ESBL-producing Enterobacterales, and KPC-producing Enterobacterales. CAZ-AVI is also an option against MDR P. aeruginosa., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...
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- 2023
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48. In vitro activity of ceftazidime-avibactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa from sub-Saharan Africa: ATLAS Global Surveillance Program 2017-2021.
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Wise MG, Karlowsky JA, Hackel MA, Harti MA, Ntshole BME, Njagua EN, Oladele R, Samuel C, Khan S, Wadula J, Lowman W, Lembede BW, and Sahm DF
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- Humans, Ceftazidime pharmacology, Ceftazidime therapeutic use, beta-Lactamases genetics, Klebsiella, South Africa, Pseudomonas aeruginosa genetics, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use
- Abstract
Objectives: To report the in vitro susceptibility of Enterobacterales (n = 3905) and Pseudomonas aeruginosa (n = 1,109) isolates, collected from patients in sub-Saharan Africa (four countries) in 2017-2021, to a panel of 10 antimicrobial agents with a focus on ceftazidime-avibactam activity against resistant phenotypes and β-lactamase carriers., Methods: MICs were determined by CLSI broth microdilution and interpreted using both 2022 CLSI and EUCAST breakpoints. β-lactamase genes were identified in select β-lactam-nonsusceptible isolate subsets using multiplex PCR assays., Results: Among Enterobacterales, 96.2% of all isolates were ceftazidime-avibactam-susceptible (MIC
90 , 0.5 µg/mL), including all serine carbapenemase-positive (n = 127), 99.6% of ESBL-positive, carbapenemase-negative (n = 730), 91.9% of multidrug resistant (MDR; n = 1817), and 42.7% of DTR (difficult-to-treat resistance; n = 171) isolates. Metallo-β-lactamase (MBL) genes were identified in most (n = 136; 91.2%) ceftazidime-avibactam-resistant isolates (3.5% of all Enterobacterales isolates). Ceftazidime-avibactam percent susceptible values ranged from 99.5% (Klebsiella species other than Klebsiella pneumoniae) to 92.5% (K. pneumoniae) for the various Enterobacterial taxa examined. Greater than 90% of Enterobacterales isolates from each country (Cameroon, Ivory Coast, Nigeria, South Africa) were ceftazidime-avibactam-susceptible. Among P. aeruginosa, 88.9% of all isolates were ceftazidime-avibactam-susceptible (MIC90 , 16 µg/mL). Most (88.5%) MBL-negative, meropenem-resistant (n = 78), 68.1% of MDR (n = 385), and 19.2% of DTR isolates (n = 99) were ceftazidime-avibactam-susceptible. MBL genes were identified in 43.1% of ceftazidime-avibactam-resistant isolates (n = 53; 4.8% of all P. aeruginosa isolates). Country-specific ceftazidime-avibactam percent susceptible values for P. aeruginosa ranged from 94.1% (Cameroon) to 76.2% (Nigeria)., Conclusion: Reference in vitro antimicrobial susceptibility testing demonstrated that most recent Enterobacterales (96%) and P. aeruginosa (89%) clinical isolates from four sub-Saharan African countries were ceftazidime-avibactam susceptible., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...- Published
- 2023
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49. Faecal carriage of multidrug-resistant and extended-spectrum β-lactamase-producing Enterobacterales in people living with HIV in Yaoundé, Cameroon.
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Dimani BD, Founou RC, Zemtsa JR, Mbossi A, Koudoum PL, Founou LL, Kouanfack C, and Sone LHE
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- Humans, Cameroon epidemiology, beta-Lactamases genetics, Feces microbiology, Escherichia coli genetics, HIV Infections complications, HIV Infections epidemiology
- Abstract
Objectives: Antibiotic resistance (AR) is a global health issue with multidimensional repercussions. There is a paucity of data regarding the molecular epidemiology of multidrug-resistant Enterobacterales (MDR-E) and extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) in Africa, especially among people living with HIV (PLHIV). This study aimed at determining the prevalence, risk factors, phenotypic and genotypic profiles of MDR-E and ESBL-PE isolated from PLHIV in Yaoundé, Cameroon., Methods: In total, samples were collected from 185 PLHIV during a three-month period (April-June 2021) at the Yaoundé Central Hospital. Stool samples and rectal swabs were collected and cultured on MacConkey agar. The API 20E kit was used for the phenotypic identification of the isolates, whereas antibiotic susceptibility testing was performed using the Kirby-Bauer disk diffusion method. The ß-lactamase genes and genotypic relatedness were studied by PCR and ERIC-PCR, respectively., Results: The prevalence of MDR-E among PLHIV was 81%, of which 39% were ESBL-PE. A high level of resistance to fosfomycin (89%), chloramphenicol (63%), and gentamicin (56%) was observed. Escherichia coli was the predominant MDR non-ESBL-PE (80.8%) and MDR ESBL-PE (73.77%). The principal ß-lactamases genes in MDR non-ESBL and MDR ESBL-PE were bla
TEM (62.90%) and blaCTX-M (40.86%), respectively. Genetic fingerprinting revealed high genetic relatedness among E. coli isolates., Conclusion: This study shows a high prevalence of MDR-E and ESBL-PE in the gut of PLHIV in Yaoundé, with blaTEM and blaCTX-M being the most prevalent. It demonstrates the need to strengthen real-time surveillance of these resistant bacteria in order to improve management of infection among PLHIV., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...- Published
- 2023
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50. Genetic characteristics of OXA-48-producing Enterobacterales from China
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Kun Ye, Jiyong Yang, Lifeng Wang, and Ling Guo
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Microbiology (medical) ,Klebsiella pneumoniae ,Immunology ,Genomics ,Biology ,Microbiology ,Genome ,beta-Lactamases ,DNA sequencing ,Carbapenemase ,Enterobacterales ,Plasmid ,Escherichia coli ,Humans ,Immunology and Allergy ,Gene ,OXA-48 ,Genetics ,Molecular epidemiology ,Outbreak ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,QR1-502 ,Klebsiella Infections ,Plasmids - Abstract
Background In China, OXA-48-producing Enterobacterales have been identified sporadically, causing only small-scale outbreaks in certain regions. This study aimed to investigate the molecular epidemiology, transmission and evolution of OXA-48-producing Enterobacterales and pOXA-48 from mainland of China.Enterobacterales METHODS: We conducted a multi-center bacterial resistance monitoring project from 2013 to 2018. The genome sequencing of OXA-48-produicng isolates was performed. Single-nucleotide polymorphism (SNP) was analysed. Eleven isolates were selected for subsequent single-molecule real-time (SMRT) sequencing. Genome sequences were annotated, and alignment of the complete sequences of the blaOXA-48-carrying plasmids from a subset of isolates that underwent long read sequencing was performed. Results A total of 41 OXA-48-producing Enterobacterales were involved in this study, including 34 K. pneumoniae, 3 E. coli, 3 E. cloacae and one K. oxytoca. OXA-48-produicng K. pneumoniae (OXAKp) ST383, ST147 and ST11 caused outbreaks of different scales in our hospital. In addition, OXA-48-producing E. coli ST156 and ST648, E. cloacae ST414 and ST418, and K. oxytoca ST34 were also identified. The blaOXA-48 gene was embedded in a Tn1999.2 structure, which was located in IncL plasmids with different sizes (63.58∼109.14 kb). Importantly, K. pneumoniae ST11 co-producing KPC-2 and OXA-48 has been identified in our hospital and it was possible that KPC-2-producing K. pneumoniae ST11 obtained the blaOXA-48-carrying plasmid during the spread. A novel blaOXA-48-carrying IncL plasmid with size of 109 kb has been identified from OXAKp ST11. It was possible that two plasmids in OXAKp ST383 were integrated to form this larger plasmid. Conclusions The OXA-48-produicng Enterobacterales were sporadic in China. Importantly, K. pneumoniae ST11 co-producing KPC-2 and OXA-48 has emerged and caused outbreak in China. This high-risk multidrug-resistant clone exhibited high compatibility and strong integration ability with foreign resistant plasmids. more...
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- 2021
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