title: In vitro selection of mutants resistant to ozenoxacin compared with levofloxacin and ciprofloxacin in Gram-positive cocci.
abstract: OBJECTIVE
  To determine the frequency of selecting mutants resistant to ozenoxacin, a des-fluoro-(6)-quinolone active against pathogens involved in skin and skin structure infections, compared with levofloxacin and ciprofloxacin in quinolone-susceptible and -resistant Gram-positive cocci.
  
  
  METHODS
  Forty-nine quinolone-susceptible and -resistant Gram-positive cocci strains with different profiles of mutations in the quinolone resistance-determining region (QRDR) were examined to determine the frequency of selecting mutants resistant to ozenoxacin compared with levofloxacin and ciprofloxacin. MICs and mutations in the QRDR were determined by standard broth microdilution and PCR amplification and sequencing, respectively.
  
  
  RESULTS
  The mean resistance rates were 3.8 × 10(-9) (range <9 × 10(-11)-1 × 10(-8)) for ozenoxacin, 9.7 × 10(-9) (range <1.1 × 10(-11)-4.2 × 10(-8)) for levofloxacin and 1.2 × 10(-8) (range <1.6 × 10(-10)-2.6 × 10(-7)) for ciprofloxacin. Spontaneous mutants resistant to ozenoxacin showed lower MICs (≤ 16 mg/L) than mutants resistant to levofloxacin and ciprofloxacin (≤ 512 mg/L). Additional mutations were observed only in ParC at Ser-80 in Staphylococcus spp., Ser-79 in Streptococcus agalactiae and Asp-83 and Ser-89 in Streptococcus pyogenes.
  
  
  CONCLUSIONS
  The probability of ozenoxacin selecting spontaneous resistant mutants in quinolone-susceptible and -resistant strains with pre-existing mutations in the QRDR is low, supporting the potential utility of ozenoxacin as a therapeutic alternative in the treatment of skin infections caused by strains highly resistant to quinolones.
authors.affiliation: Centre for International Health Research (CRESIB), Barcelona, Spain Department of Clinical Microbiology, Hospital Clinic, School of Medicine, University of Barcelona, Barcelona, Spain Spanish Network for Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: López
authors.affiliation: Spanish Network for Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Madrid, Spain Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Tato
authors.affiliation: Centre for International Health Research (CRESIB), Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Espinal
authors.affiliation: Ferrer Laboratories, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Garcia-Alonso
authors.affiliation: Ferrer Laboratories, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Gargallo-Viola
authors.affiliation: Spanish Network for Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Madrid, Spain Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Cantón
authors.affiliation: Centre for International Health Research (CRESIB), Barcelona, Spain Department of Clinical Microbiology, Hospital Clinic, School of Medicine, University of Barcelona, Barcelona, Spain Spanish Network for Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Madrid, Spain jvila@ub.edu.
authors.forename: J
authors.initials: J
authors.lastname: Vila
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006095:Gram-Positive Cocci / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D064704:Levofloxacin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D016133:Polymerase Chain Reaction; D015363:Quinolones / Q000494:pharmacology*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D000631:Aminopyridines; D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D015363:Quinolones; D002939:Ciprofloxacin; D064704:Levofloxacin; C000592413:ozenoxacin
keywords: QRDRs; mutation rates; non-fluorinated quinolones