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1998 Fiscal Year Final Research Report Summary

Emergence of vancomycin-resistant MRSA and its countermesures

Research Project

Project/Area Number 09470078
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionJuntendo University

Principal Investigator

HIRAMATSU Keiichi  Juntendo university the medical department Professor, 医学部, 教授 (10173262)

Co-Investigator(Kenkyū-buntansha) SASAKI Kazumi  Juntendo university the medical department Assistant, 医学部, 助手
堀 典子  順天堂大学, 医学部, 助手 (50245700)
KUWAHARA Kyoko  Juntendo university the medical department Assistant, 医学部, 助手 (10167976)
HANAKI Hideaki  Juntendo university the medical department Lecture, 医学部, 講師 (60286747)
ITO Teruyo  Juntendo university the medical department Lecture, 医学部, 講師 (10095763)
KONDO Noriko  Juntendo university the medical department Assistant
Project Period (FY) 1997 – 1998
KeywordsVRSA / hetero-VRSA / vancomycin / Staphylococcus aureus / peptidoglycan / cell wall / teicoplanin / glycopeptide
Research Abstract

The mechanism of vancomycin resistance was looked for with the vancomycin-resistant Staphylococcus aureus strain Mu5O and the heterogeneously vancomycin-resistant Staphylococcus aureus strain Mu3. The cell wall synthesis of these strains were activated as demonstrated with accelerated incorporation of N-acetylglucosamine into the cell wall, increased intracellular murein monomer precursor pooi, and increased cell wall thickness. Biochemical analysis of cell wall peptidoglycan showed decreased cross-linking, which correlated with 2.4 times increased vancomycin binding to the purified peptidoglycan of Mu5O as compared with that of vancomycin-susceptible strains of MRSA as well as MSSA.Incidence of hetero-VRSA was 9.3% of all MRSA isolates in university hospitals in Japan and 1.3% in non-uuniversity hospitals and clinics. Since we have shown that hetero-VRSA spontaneously generates VRSA at a high frequency of 1 in 1,000,000 on vancomycin selection, and hetero-VRSA itself causes vancomyicn therapeutic failure, the situation was interpreted as a greatly alarming one. A combination therapy against MRSA strains (sulbactam/ampicillin plus arbekacin) was developed to counter failure of vancomycin therapy. Several cases were experienced with this treatment regimen with success. Teicoplanin, a newly introduced glycopeptide, was found out to have less antimicrobial acitivity against hetero-VRSA and VRSA than vancomycin. Thus, development of novel therapeutic agents against VRSA is an urgent task.

  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Hiramatsu, K.: "The emergence of staphylococcus aureus with reduced susceptibility to vancomycin in Japan." Am.J.Med.104. 7S-10S (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka, M.: "In-vitro activity of Du-6859a against methicillin-resistaut Staphylococcus aureus isolates with reduced susceptibility to vancomycin." J.Antimicrob. Chemother.42. 552-553 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hanaki, H.: "Activated cell-wall synthesis is associated with vancomycin resistance in methicillin-resistant Staphylococcus aureus clinical strains Mu3 and Mu50." J.Antimicrob. chemother.42. 199-209 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hanaki, H.: "Increase in the deaminated muropeptides in the peptidoglycan of vancomycin-resistant Staphylococcus aureus(VRSA) strain Mu50." J.Antimicrob. chemother.42. 315-320 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tenover, F.C.: "Characterization of staphylococci with reduced susceptibility to vancomycin and other glycopeptides." J.Clinical Microbiology. 36. 1020-1027 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiramatsu, K.: "Vancomycin resistance in Staphylococci." Drug Res.Updates.1. 135-150 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiramatsu, K.: "Current research on the epidemiology, biochemistry, and therapeutic possibilities for vancomycin-resistant Staphylococcus aureus." Antibiots. Chemotherapy. 2. 13-13 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Cui, L-Z.: "Postoperative toxic shock syndrome caused by a highly virulent methicillin-resistant Staphylococcus aureus syrain." Scandinavian J.of Intectious Diseases.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito, T.: "Acquisition of methicillin resistance and progression of multi-antibiotic resistance in methicillin-resistant Staphylococcus aureus." Yunsei Medical Journal on Antimicrobial Resistance. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hanaki, H.: "Glyco peptide resistance in Staphylococci." Antimicrobial Agent and Chemotherapy. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hanaki, H.: "Petection methol of glycopeptide-resistant Staphylococcus aureus." Methods in Molecular Medicine. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平松啓一: "耐性菌感染症の理論と実際" 医薬ジャーナル社, (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平松啓一: "新微生物と化学療法" 薬業事報社, (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平松啓一: "抗生物質が効かない" 集英社, 270 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiramatsu, K.: "The Emergence of Staphylococcus aureus With Reduced Susceptibility to Vancomycin in Japan." Am.J.Med.104(5A). 7S-10S (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka, M.: "In-vitro activity of DU-6859a against methicillin-resistant Staphylococcus aureus isolates with reduced susceptibility to vancomycin." J.Antimicrob.Chemother. 42. 552-553 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hanaki, H.: "Activated cell-wall synthesis is associated with vancomycin resistance in methicillin-resistant Staphylococcus aureus clinical strains Mu3 and Mu50" J.Antimicrob.Chemother.42. 199-209 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hanaki, H.: "Increase in the deamidated muropeptides in the peptidoglycan of vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50." J.Antimicrob.Chemother. 42. 315-320 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukuda, H.: "Antibacterial activity of gatifloxacin, a newly developed fluoroquinolone, against sequentially acquired quinolone-resistant mutants and the norA transformant of Staphylococcus aureus." Antimicribial Agents and Chemotherapy. 42. 1917-1922 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tenover, F.C.: "Characterization of staphylococci with reduced susceptibility to vancomycin and other glycopeptides." Journal of Clinical Microbiology. 36. 1020-1027 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiramatsu, K.: "Vancomycin resistance in staphylococci" Drug Res.Updates.1. 135-150 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiramatsu, K: "Current research on the epidemiology, biochemistry, and therapeutic possibilities for vancomycin-resistant Staphylococcus aureus." Antibiots Chemotherapy.2. 13 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Cui, I-Z (LongZhu).: "Postoperative toxic shock syndrome caused by a highly virulent methicillin-resistant Staphylococcus aureus strain." Scandinavian J.of Infectious Diseases.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito, T.: "Acquisition of methicillin resistance and progression of multi-anitibiotic resistance in methicillin-resistant Staphylococcus aureus." Yunsei Medical Journal on Antimicrobial Resistance.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hanaki, H.: "Glycopeptide resistance in staphylococci. Antimicrobial Agents and Chemotherapy" vol.3(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hanaki, H.: "Detection method of glycopeptide-resistant Staphylococcus aureus." in Methods in Molecular Medicine.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiramatsu, K.: "Evolution of methicillin and glycopeptide resistance in Staphylococcus aureus." in Bailliere's Clinical Infectious Disease.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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