title: Emergence of a daptomycin-non-susceptible Enterococcus faecium strain that encodes mutations in DNA repair genes after high-dose daptomycin therapy.
abstract: BACKGROUND
  An increasing number of reports have documented the emergence of daptomycin-nonsusceptible Enterococcus in patients during daptomycin therapy. Even though several mechanisms for daptomycin-nonsusceptibility have been suggested, the potential genetic mutations which might contribute to the daptomycin-nonsusceptibility are not fully understood.
  
  
  METHODS
  We isolated a vancomycin-susceptible, daptomycin nonsusceptible Enterococcus faecium strain from a patient with acute lymphocytic leukemia who received high-dose daptomycin therapy for E. faecium endocarditis. Whole-genome sequencing analysis revealed mutations within genes encoding DNA repair proteins MutL and RecJ of the daptomycin-nonsusceptible Enterococcus strain which might have facilitated its emergence.
  
  
  CONCLUSIONS
  We identified the mutations of DNA mismatch repair genes in a clinical isolate of daptomycin nonsusceptible E. faecium which emerged in spite of high-dose daptomycin therapy. The finding implicates the possible association of DNA repair mechanism and daptomycin resistance. Careful monitoring is necessary to avoid the emergence of daptomycin non-susceptible isolates of E. faecium and particularly in cases of long-term daptomycin use or in immunocompromised patients.
authors.affiliation: Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matono
authors.affiliation: Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan. kayokohayakawa@gmail.com.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Hayakawa
authors.affiliation: Department of Hematology, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Risen
authors.initials: R
authors.lastname: Hirai
authors.affiliation: Department of Hematology, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tanimura
authors.affiliation: Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujiya
authors.affiliation: Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Mawatari
authors.affiliation: Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kutsuna
authors.affiliation: Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Takeshita
authors.affiliation: Microbiology Laboratory, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Mezaki
authors.affiliation: Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Ohmagari
authors.affiliation: Pathogenic Microbe Laboratory, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Miyoshi-Akiyama
mesh_terms: D000328:Adult; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D017576:Daptomycin / Q000008:administration & dosage* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D016984:Enterococcus faecium / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*
chemical_list: D017576:Daptomycin
keywords: Daptomycin; E. faecium; Whole-genome sequence