Dataset Information

Two Cases of Vancomycin-Resistant Enterococcus faecium Bacteremia With Development of Daptomycin-Resistant Phenotype and its Detection Using Oxford Nanopore Sequencing.

ABSTRACT: In this work, we report 2 cases of vancomycin-resistant Enterococcus faecium bacteremia with development of daptomycin resistance in 2 patients with acute myeloid leukemia and myelodysplastic syndrome. Mutations related to daptomycin-nonsusceptible phenotype in liaSR genes were found in all strains of the study, including those with a minimum inhibitory concentration?<1 µg/mL collected before daptomycin therapy. Epidemiological investigation using core genome single nucleotide polymorphism and core genome multilocus sequence typing revealed clonality of all the isolates. In this study, we conclude that real-time genome sequencing of clinical isolates can provide rapid access to timely information on daptomycin-resistant genotypes that would help clinicians speed up and optimize the selection of the antibiotic for treatment.

SUBMITTER: Udaondo Z

PROVIDER: S-EPMC7291683 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Two Cases of Vancomycin-Resistant Enterococcus faecium Bacteremia With Development of Daptomycin-Resistant Phenotype and its Detection Using Oxford Nanopore Sequencing.

Udaondo Zulema Z Jenjaroenpun Piroon P Wongsurawat Thidathip T Meyers Erik E Anderson Courtney C Lopez James J Mohan Meera M Tytarenko Ruslana R Walker Brian B Ussery David D Kothari Atul A Jun Se-Ran SR

Open forum infectious diseases 20200523 6

In this work, we report 2 cases of vancomycin-resistant Enterococcus faecium bacteremia with development of daptomycin resistance in 2 patients with acute myeloid leukemia and myelodysplastic syndrome. Mutations related to daptomycin-nonsusceptible phenotype in liaSR genes were found in all strains of the study, including those with a minimum inhibitory concentration <1 µg/mL collected before daptomycin therapy. Epidemiological investigation using core genome single nucleotide poly ...[more]

PMID: 32550237

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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

Two Cases of Vancomycin-Resistant Enterococcus faecium Bacteremia With Development of Daptomycin-Resistant Phenotype and its Detection Using Oxford Nanopore Sequencing.

Publications

Two Cases of Vancomycin-Resistant <i>Enterococcus faecium</i> Bacteremia With Development of Daptomycin-Resistant Phenotype and its Detection Using Oxford Nanopore Sequencing.

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