Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
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.
J Antimicrob Chemother. 2016 Jul;71(7):1807-14. doi: 10.1093/jac/dkw060. Epub 2016 Mar 10.
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.
金黄色葡萄球菌小菌落变异体（SCVs）与持续性和耐药感染有关。我们首次证明在万古霉素中介金黄色葡萄球菌（VISA）感染患者中，在长期使用达托霉素治疗期间出现 SCVs。
一名 73 岁男性患有败血症性关节炎，感染了 VISA。患者接受达托霉素治疗；然而，患者仍感染 VISA，在长期治疗期间，他的血液中持续分离出 VISA。通过 PFGE、包括葡萄球菌盒染色体 mec（SCCmec）、spa 和 MLST 的基因分型、抗菌药物敏感性测试以及扫描和透射电子显微镜对 5 株 VISA 分离株进行了特征描述。还进行了 WGS 和脂肪酸分析。
这 5 株 VISA 分离株来自 ST239/spa3(t037)的单个克隆，其中前 3 株为 SCCmecIII 阳性和达托霉素敏感，而最后 2 株为 SCCmecIII 阴性和达托霉素耐药，表现出 SCVs 的特征。第一和最后分离株在 SCCmec 和 mprF、cls2、clpX 和 fabF 基因中显示出 13 个显著的遗传差异。其中，fabF（编码脂肪酸合酶）的突变似乎部分导致了 SCVs 的生长缓慢和超微结构特征，包括异常的细胞间物质，以及达托霉素耐药性。
我们首次在使用达托霉素治疗的败血症性关节炎患者中发现 VISA 的 SCVs。VISA 的达托霉素耐药性 SCVs 是逐步进化而来的，fabF 的突变可能导致其物理和超微结构特征以及达托霉素耐药性。
