Whole-genome sequencing was used to examine a persistent E. faecium bacteremia that acquired heteroresistance to three antibiotics in response to prolonged multidrug therapy. Comparison of 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 progressive loss of vancomycin resistance after withdrawal of the drug.
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