Dataset Information

Emergence of Vancomycin-Resistant Enterococcus faecium at an Australian Hospital: A Whole Genome Sequencing Analysis.

ABSTRACT: In 2015, a marked increase in vancomycin-resistant Enterococcus faecium (VREfm) isolation was detected at the Royal Hobart Hospital, Australia. The primary objective of this work was to examine the dynamics of VREfm transmission using whole genome data mapped to public health surveillance information. Screening and clinical isolates of VREfm from patients were typed for the specific vancomycin-resistance locus present. Of total isolates collected from 2014-2016 (n?=?222), 15.3% and 84.7% harboured either the vanA or the vanB vancomycin-resistance locus, respectively. Whole-genome sequencing of 80 isolates was performed in conjunction with single-nucleotide polymorphic (SNP) analysis and in silico multi-locus sequence typing (MLST). Among the isolates sequenced, 5 phylogenetic clades were identified. The largest vanB clade belonged to MLST sequence type ST796 and contained clinical isolates from VREfm infections that clustered closely with isolates from colonised patients. Correlation of VREfm genotypes with spatio-temporal patient movements detected potential points of transmission within the hospital. ST80 emerged as the major vanA sequence type for which the most likely index case of a patient cluster was ascertained from SNP analyses. This work has identified the dominant clones associated with increased VREfm prevalence in a healthcare setting, and their likely direction of transmission.

SUBMITTER: Leong KWC

PROVIDER: S-EPMC5908837 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Emergence of Vancomycin-Resistant Enterococcus faecium at an Australian Hospital: A Whole Genome Sequencing Analysis.

Leong Kelvin W C KWC Cooley Louise A LA Anderson Tara L TL Gautam Sanjay S SS McEwan Belinda B Wells Anne A Wilson Fiona F Hughson Lucy L O'Toole Ronan F RF

Scientific reports 20180419 1

In 2015, a marked increase in vancomycin-resistant Enterococcus faecium (VREfm) isolation was detected at the Royal Hobart Hospital, Australia. The primary objective of this work was to examine the dynamics of VREfm transmission using whole genome data mapped to public health surveillance information. Screening and clinical isolates of VREfm from patients were typed for the specific vancomycin-resistance locus present. Of total isolates collected from 2014-2016 (n = 222), 15.3% and 84.7% harbour ...[more]

PMID: 29674657

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Project description:BackgroundVancomycin-resistant Enterococcus faecium (VREfm) is a leading cause of nosocomial infection. Here, we describe the utility of whole-genome sequencing in defining nosocomial VREfm transmission.MethodsA retrospective study at a single hospital in the United Kingdom identified 342 patients with E. faecium bloodstream infection over 7 years. Of these, 293 patients had a stored isolate and formed the basis for the study. The first stored isolate from each case was sequenced (200 VREfm [197 vanA, 2 vanB, and 1 isolate containing both vanA and vanB], 93 vancomycin-susceptible E. faecium) and epidemiological data were collected. Genomes were also available for E. faecium associated with bloodstream infections in 15 patients in neighboring hospitals, and 456 patients across the United Kingdom and Ireland.ResultsThe majority of infections in the 293 patients were hospital-acquired (n = 249) or healthcare-associated (n = 42). Phylogenetic analysis showed that 291 of 293 isolates resided in a hospital-associated clade that contained numerous discrete clusters of closely related isolates, indicative of multiple introductions into the hospital followed by clonal expansion associated with transmission. Fine-scale analysis of 6 exemplar phylogenetic clusters containing isolates from 93 patients (32%) identified complex transmission routes that spanned numerous wards and years, extending beyond the detection of conventional infection control. These contained both vancomycin-resistant and -susceptible isolates. We also identified closely related isolates from patients at Cambridge University Hospitals NHS Foundation Trust and regional and national hospitals, suggesting interhospital transmission.ConclusionsThese findings provide important insights for infection control practice and signpost areas for interventions. We conclude that sequencing represents a powerful tool for the enhanced surveillance and control of nosocomial E. faecium transmission and infection.

Project description:Enterococcus faecium clinical isolates A902 and BM4538, which were resistant to relatively high levels of vancomycin (128 and 64 microg/ml, respectively) and to low levels of teicoplanin (4 microg/ml), and Enterococcus faecalis clinical isolates BM4539 and BM4540, which were resistant to moderate levels of vancomycin (16 microg/ml) and susceptible to teicoplanin (0.25 microg/ml), were studied. They were constitutively resistant by synthesis of peptidoglycan precursors ending with d-alanyl-d-lactate and harbored a chromosomal vanD gene cluster which was not transferable by conjugation to other enterococci. VanX(D) activity, which is not required in the absence of d-Ala-d-Ala, was low in the four strains, although none of the conserved residues was mutated; and the constitutive VanY(D) activity in the membrane fractions was inhibited by penicillin G. The mutations E(13)G in the region of d-alanine:d-alanine ligase (which is implicated in d-Ala1 binding in A902) and S(319)N of the serine involved in ATP binding in BM4538 and a 7-bp insertion at different locations in BM4539 and BM4540 (which led to putative truncated proteins) led to the production of an impaired enzyme and accounted for the lack of d-Ala-d-Ala-containing peptidoglycan precursors. The same 7-bp insertion in vanS(D) of BM4539 and BM4540 and a 1-bp deletion in vanS(D) of A902, which in each case led to a putative truncated and presumably nonfunctional protein, could account for the constitutive resistance. Strain BM4538, with a functional VanS(D), had a G(140)E mutation in VanR(D) that could be responsible for constitutive glycopeptide resistance. This would represent the first example of constitutive van gene expression due to a mutation in the structural gene for a VanR transcriptional activator. Study of these four additional strains that could be distinguished on the basis of their various assortments of mutations confirmed that all VanD-type strains isolated so far have mutations in the ddl housekeeping gene and in the acquired vanS(D) or vanR(D) gene that lead to constitutive resistance to vancomycin.

Dataset Information

Emergence of Vancomycin-Resistant Enterococcus faecium at an Australian Hospital: A Whole Genome Sequencing Analysis.

Publications

Emergence of Vancomycin-Resistant Enterococcus faecium at an Australian Hospital: A Whole Genome Sequencing Analysis.

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