Genetic Basis of Emerging Vancomycin, Linezolid, and Daptomycin Heteroresistance in a Case of Persistent Enterococcus faecium Bacteremia

Antimicrob Agents Chemother. 2018 Mar 27;62(4):e02007-17. doi: 10.1128/AAC.02007-17. Print 2018 Apr.


Whole-genome sequencing was used to examine a persistent Enterococcus faecium bacteremia that acquired heteroresistance to three antibiotics in response to prolonged multidrug therapy. A comparison of the complete genomes before and after each change revealed the emergence of known resistance determinants for vancomycin and linezolid and suggested that a novel mutation in fabF, encoding a fatty acid synthase, was responsible for daptomycin nonsusceptibility. Plasmid recombination contributed to the progressive loss of vancomycin resistance after withdrawal of the drug.

Keywords: E. faecium; VRE; daptomycin; fabF; heteroresistance; linezolid; vancomycin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bacteremia / microbiology*
  • Daptomycin / pharmacology*
  • Drug Resistance, Multiple, Bacterial / genetics
  • Drug Therapy, Combination
  • Enterococcus faecium / drug effects*
  • Enterococcus faecium / genetics*
  • Humans
  • Linezolid / pharmacology*
  • Male
  • Microbial Sensitivity Tests
  • Vancomycin / pharmacology*
  • Vancomycin Resistance / genetics


  • Vancomycin
  • Linezolid
  • Daptomycin