title: Emergence of a small colony variant of vancomycin-intermediate Staphylococcus aureus in a patient with septic arthritis during long-term treatment with daptomycin.
abstract: Small colony variants (SCVs) of Staphylococcus aureus are associated with persistent and drug-resistant infections. We demonstrated for the first time the emergence of SCVs in a patient with vancomycin-intermediate S. aureus (VISA) infection during long-term treatment with daptomycin.
  
  
  
  A 73-year-old man with septic arthritis was infected with VISA. The patient was treated with daptomycin; however, the patient remained infected with VISA, with continuous isolation of VISA from his blood during long-term treatment. Five VISA isolates were characterized by: PFGE; genotyping including staphylococcal cassette chromosome mec (SCCmec), spa and MLST; antimicrobial susceptibility testing; and scanning and transmission electron microscopy. WGS and fatty acid analysis were also performed.
  
  
  
  The five VISA isolates were from a single clone of ST239/spa3(t037) and, of these, the first three were SCCmecIII positive and daptomycin susceptible, whereas the last two were SCCmecIII negative and daptomycin resistant and exhibited the characteristics of SCVs. The first and last isolates showed 13 remarkable genetic differences in SCCmec and the mprF, cls2, clpX and fabF genes. Of these, mutation of fabF (encoding the fatty acid synthase) seemed to be partially responsible for the slow growth and ultrastructural features, including an abnormal intercellular substance, and for the daptomycin resistance of SCVs.
  
  
  
  For the first time, we identified SCVs of VISA in a patient with septic arthritis during long-term treatment with daptomycin. Daptomycin-resistant SCVs of VISA were evolved in a stepwise manner and the mutation of fabF is likely responsible for the physical and ultrastructural characteristics and daptomycin resistance.
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jui-Chang
authors.initials: JC
authors.lastname: Tsai
authors.affiliation: Department of Epidemiology, Genomics and Evolution, International Medical Education and Research Center, Niigata, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Hsiao-Jan
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Hung
authors.affiliation: Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Po-Ren
authors.initials: PR
authors.lastname: Hsueh
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan ljteng@ntu.edu.tw.
authors.forename: Lee-Jene
authors.initials: LJ
authors.lastname: Teng
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001170:Arthritis, Infectious / Q000188:drug therapy / Q000382:microbiology*; D017576:Daptomycin / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D005838:Genotype; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D058885:Multilocus Sequence Typing; D010641:Phenotype; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification / Q000648:ultrastructure; D013995:Time; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D017576:Daptomycin