Dataset Information

Prevalence and Genetic Analysis of Resistance Mechanisms of Linezolid-Nonsusceptible Enterococci in a Tertiary Care Hospital Examined via Whole-Genome Sequencing.

ABSTRACT: (1) Background: Linezolid plays an important role in the treatment of invasive infections caused by vancomycin-resistant enterococci after its introduction to clinical practice. However, a detailed examination of linezolid-nonsusceptible enterococci (LNSE) is required. In this study, we attempted to analyze the mechanisms of LNSE strains isolated from a tertiary care hospital. (2) Methods: From 2019 to 2020, 18 Enterococcus faecalis, 14 E. faecium, and 2 E. gallinarum clinical isolates were collected at Severance Hospital. Agar dilution was performed to evaluate precise linezolid minimum inhibitory concentrations (MICs). Short-read whole-genome sequencing (WGS) was used to analyze resistance determinants. (3) Results: The presence of the optrA gene was likely the primary resistance mechanism in these three species, typically demonstrating a MIC value of 8 μg/mL. The co-existence of the cfr(D) and poxtA2 gene was the second major mechanism, primarily predicting a phenotype showing intermediate susceptibility to linezolid. G2576U mutation on 23S rRNA was only found in E. faecium; it mediated the most significant increase in linezolid MIC. (4) Conclusion: This is the first report examining poxtA2-cfr(D) co-harboring clinical enterococcal isolates in Korea and demonstrating the poxtA EF9F6-harboring clinical E. gallinarum strain worldwide. The comparison with resistance-gene-containing fragments in the isolates obtained from different countries and different sources demonstrated the spread of linezolid-resistance genes and suggested the possibility of foodborne transmission.

SUBMITTER: Hu Y

PROVIDER: S-EPMC9686573 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Prevalence and Genetic Analysis of Resistance Mechanisms of Linezolid-Nonsusceptible Enterococci in a Tertiary Care Hospital Examined via Whole-Genome Sequencing.

Hu Yuxin Y Won Dongju D Nguyen Le Phuong LP Osei Kennedy Mensah KM Seo Younghee Y Kim Junglim J Lee Yoonhee Y Lee Hyukmin H Yong Dongeun D Choi Jong Rak JR Lee Kyungwon K

Antibiotics (Basel, Switzerland) 20221114 11

(1) Background: Linezolid plays an important role in the treatment of invasive infections caused by vancomycin-resistant enterococci after its introduction to clinical practice. However, a detailed examination of linezolid-nonsusceptible enterococci (LNSE) is required. In this study, we attempted to analyze the mechanisms of LNSE strains isolated from a tertiary care hospital. (2) Methods: From 2019 to 2020, 18 Enterococcus faecalis, 14 E. faecium, and 2 E. gallinarum clinic ...[more]

PMID: 36421268

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Project description:UNLABELLED:Linezolid resistance is uncommon among staphylococci, but approximately 2% of clinical isolates of coagulase-negative staphylococci (CoNS) may exhibit resistance to linezolid (MIC, ?8 µg/ml). We performed whole-genome sequencing (WGS) to characterize the resistance mechanisms and genetic backgrounds of 28 linezolid-resistant CoNS (21 Staphylococcus epidermidis isolates and 7 Staphylococcus haemolyticus isolates) obtained from blood cultures at a large teaching health system in California between 2007 and 2012. The following well-characterized mutations associated with linezolid resistance were identified in the 23S rRNA: G2576U, G2447U, and U2504A, along with the mutation C2534U. Mutations in the L3 and L4 riboproteins, at sites previously associated with linezolid resistance, were also identified in 20 isolates. The majority of isolates harbored more than one mutation in the 23S rRNA and L3 and L4 genes. In addition, the cfr methylase gene was found in almost half (48%) of S. epidermidis isolates. cfr had been only rarely identified in staphylococci in the United States prior to this study. Isolates of the same sequence type were identified with unique mutations associated with linezolid resistance, suggesting independent acquisition of linezolid resistance in each isolate. IMPORTANCE:Linezolid is one of a limited number of antimicrobials available to treat drug-resistant Gram-positive bacteria, but resistance has begun to emerge. We evaluated the genomes of 28 linezolid-resistant staphylococci isolated from patients. Multiple mutations in the rRNA and associated proteins previously associated with linezolid resistance were found in the isolates investigated, underscoring the multifocal nature of resistance to linezolid in Staphylococcus. Importantly, almost half the S. epidermidis isolates studied harbored a plasmid-borne cfr RNA methylase gene, suggesting that the incidence of cfr may be higher in the United States than previously documented. This finding has important implications for infection control practices in the United States. Further, cfr is commonly detected in bacteria isolated from livestock, where the use of phenicols, lincosamides, and pleuromutilins in veterinary medicine may provide selective pressure and lead to maintenance of this gene in animal bacteria.

Dataset Information

Prevalence and Genetic Analysis of Resistance Mechanisms of Linezolid-Nonsusceptible Enterococci in a Tertiary Care Hospital Examined via Whole-Genome Sequencing.

Publications

Prevalence and Genetic Analysis of Resistance Mechanisms of Linezolid-Nonsusceptible Enterococci in a Tertiary Care Hospital Examined via Whole-Genome Sequencing.

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