title: Microbiological and clinical study of methicillin-resistant Staphylococcus aureus (MRSA) carrying VraS mutation: changes in susceptibility to glycopeptides and clinical significance.
abstract: The VraSR two-component regulatory system is involved in glycopeptide resistance in Staphylococcus aureus. We examined the relationship between VraS mutation and susceptibility to various antimicrobial agents in 400 clinical isolates of methicillin-resistant S. aureus (MRSA) from Cancer Institute Hospital between 1998 and 2004. The prevalence of MRSA isolates with teicoplanin minimum inhibitory concentrations (MICs) of 4-8 microg/mL rose between 2000 and 2002 (52% in 2000). Among the isolates displaying reduced susceptibility to teicoplanin (78 isolates), 99% harboured the Ile5Asn (I5N) mutation in VraS. In addition, MICs of oxacillin and imipenem tended to be higher for I5N mutants compared with those for non-I5N isolates. By contrast, no significant change was noted in susceptibility to arbekacin or vancomycin. In this hospital, I5N mutants emerged at an early stage after the introduction of teicoplanin and thereafter declined in number upon increased usage of arbekacin instead of glycopeptides. Outcomes from 18 patients who were infected with MRSA with reduced susceptibility to teicoplanin were analysed microbiologically in a retrospective manner. Teicoplanin was effective in 50% of the patients treated with this drug. On the other hand, arbekacin and vancomycin were effective in all cases. The results indicate the relationship between antimicrobial susceptibility and therapeutic effect.
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan. yoshihisa_kato@meiji.co.jp
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kato
authors.forename: Takahisa
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Ida
authors.forename: Kazunori
authors.initials: K
authors.lastname: Maebashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Sakurai
authors.forename: Joji
authors.initials: J
authors.lastname: Shiotani
authors.forename: Izumi
authors.initials: I
authors.lastname: Hayashi
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D000617:Aminoglycosides / Q000494:pharmacology / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D003982:Dibekacin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D008297:Male; D016106:Methicillin Resistance / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D010068:Oxacillin / Q000494:pharmacology; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006020:Glycopeptides; C478169:VraS protein, Staphylococcus aureus; D003982:Dibekacin; D015378:Imipenem; C031986:arbekacin; D010068:Oxacillin