Dataset Information

Challenges in interpretation of WGS and epidemiological data to investigate nosocomial transmission of vancomycin-resistant Enterococcus faecium in an endemic region: incorporation of patient movement network and admission screening.

ABSTRACT:

Objectives

VRE are listed, by the WHO, among the leading resistant pathogens causing greatest public concern; hence the spread and transmission of VRE, especially in hospitalized patients, need to be monitored. Despite the advancements in typing methods since the implementation of WGS for outbreak investigations, data interpretation, especially for vancomycin-resistant Enterococcus faecium (VREfm) in an endemic setting, remains challenging. In this study we explored the potential added benefit of incorporating patient movement data and admission screening to accurately estimate the magnitude of an outbreak.

Methods

We sequenced 73 VREfm isolates from patients with bacteraemia (n = 43) and rectal colonization (n = 30/32). Genetic relatedness was determined by SNP distance (≤10) between isolates. Patient movements were visualized in a movement network, along with contact intensity and rectal colonization status prior to infection onset.

Results

ST117, ST80 and ST203 were the predominant STs in our study population. Forty-four percent (18/41) of VREfm bacteraemia cases were of endogenous origin. SNP analysis of infection and colonization isolates revealed nine clonal groups. Eighty-six percent (37/43) of the patients were visualized in a transmission network due to spatiotemporal overlap. Nineteen out of 43 (44%) belonged to five transmission clusters. Incorporation of prior colonization status revealed that transmission was very likely in only 63% (12/19) of patients in these transmission clusters.

Discussion

Although interpretation of WGS data is challenging, incorporation of patient movement data and colonization status by admission screening of high-risk patients may provide additional resolution when interpreting the magnitude of an outbreak in an endemic setting.

SUBMITTER: Eichel V

PROVIDER: S-EPMC7303815 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Challenges in interpretation of WGS and epidemiological data to investigate nosocomial transmission of vancomycin-resistant Enterococcus faecium in an endemic region: incorporation of patient movement network and admission screening.

Eichel Vanessa V Klein Sabrina S Bootsveld Carolin C Frank Uwe U Heeg Klaus K Boutin Sébastien S Nurjadi Dennis D

The Journal of antimicrobial chemotherapy 20200701 7

<h4>Objectives</h4>VRE are listed, by the WHO, among the leading resistant pathogens causing greatest public concern; hence the spread and transmission of VRE, especially in hospitalized patients, need to be monitored. Despite the advancements in typing methods since the implementation of WGS for outbreak investigations, data interpretation, especially for vancomycin-resistant Enterococcus faecium (VREfm) in an endemic setting, remains challenging. In this study we explored the potential added b ...[more]

PMID: 32413123

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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

Challenges in interpretation of WGS and epidemiological data to investigate nosocomial transmission of vancomycin-resistant Enterococcus faecium in an endemic region: incorporation of patient movement network and admission screening.

Objectives

Methods

Results

Discussion

Publications

Challenges in interpretation of WGS and epidemiological data to investigate nosocomial transmission of vancomycin-resistant Enterococcus faecium in an endemic region: incorporation of patient movement network and admission screening.

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