title: Correlation between the activity of different fluoroquinolones and the presence of mechanisms of quinolone resistance in epidemiologically related and unrelated strains of methicillin-susceptible and -resistant Staphylococcus aureus.
abstract: OBJECTIVE
  To study the activity of five different fluoroquinolones against 22 epidemiologically related and unrelated strains of Staphylococcus aureus (13 methicillin-resistant (MRSA) strains and nine methicillin-susceptible (MSSA) strains) in which the mechanisms of quinolone resistance are also investigated.
  
  
  METHODS
  The MICs of the different fluoroquinolones were determined by the microdilution method, in the presence and absence of reserpine. The quinolone resistance-determining regions of the gyrA, gyrB, grlA and grlB genes were amplified and sequenced to establish the presence of mutations. The molecular epidemiology of the 22 strains was performed by low-frequency restriction analysis of chromosomal DNA with SmaI.
  
  
  RESULTS
  MSSA strains showed lower homology than MRSA strains, in which only two clones were seen. Trovafloxacin showed the best activity against these clinical isolates of S. aureus, since strains carrying one amino acid change in both GyrA and GrlA subunits remained susceptible to this antimicrobial agent. Furthermore, trovafloxacin did not seem to be a substrate for NorA.
  
  
  CONCLUSIONS
  Trovafloxacin was the most active quinolone tested against S. aureus strains, followed by levofloxacin and sparfloxacin, whereas ciprofloxacin and norfloxacin were the least active quinolones, in both the presence and absence of reserpine. Epidemiologically related S. aureus strains presented different mechanisms of quinolone resistance, suggesting a divergent evolution of the same clone. Finally, 16 S. aureus strains with a ciprofloxacin plus reserpine MIC > or = 1 mg/L already showed a mutation in the grlA gene. This MIC may be useful as a marker of mutation in this gene, contraindicating the use of this quinolone, since a second mutation may develop during treatment.
authors.affiliation: Institut Clínic d'Infeccions i Immunologia, IDIBAPS, Departament de Microbiologia, Facultat de Medicina, Hospital Clínic, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Sierra
authors.forename: F
authors.initials: F
authors.lastname: Marco
authors.forename: J
authors.initials: J
authors.lastname: Ruiz
authors.forename: M T
authors.initials: MT
authors.lastname: Jiménez de Anta
authors.forename: J
authors.initials: J
authors.lastname: Vila
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D027081:DNA Gyrase / Q000235:genetics / Q000378:metabolism; D027101:DNA Topoisomerase IV / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D016521:Electrophoresis, Gel, Pulsed-Field; D024841:Fluoroquinolones; D006801:Humans; D016106:Methicillin Resistance / Q000235:genetics / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000453:epidemiology; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects* / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase