title: Impact of qnrA1, qnrB1 and qnrS1 on the efficacy of ciprofloxacin and levofloxacin in an experimental pneumonia model caused by Escherichia coli with or without the GyrA mutation Ser83Leu.
abstract: OBJECTIVE
  The aim of this study was to evaluate the impact of qnrA1, qnrB1 and qnrS1 on the in vivo efficacies of ciprofloxacin and levofloxacin in an experimental model of pneumonia caused by Escherichia coli.
  
  
  METHODS
  Two isogenic groups of E. coli transformants, based on two ATCC 25922 strains, with or without the GyrA mutation Ser83Leu, and carrying qnrA1, qnrB1 or qnrS1, were used in an experimental pneumonia model. The efficacies of ciprofloxacin (40 mg/kg/day) and levofloxacin (50 and 150 mg/kg/day) were evaluated.
  
  
  RESULTS
  For the pneumonia caused by the parental strains lacking qnr genes, both fluoroquinolones significantly (P<0.05) reduced the bacterial lung concentration by >7 log10 cfu/g against E. coli ATCC/pBK and between 5.09 and 6.34 log10 cfu/g against E. coli ATCC-S83L/pBK. The presence of any qnr genes in the strains of both isogenic groups diminished the reduction of bacterial lung concentration with any therapy (P<0.05). Furthermore, all therapeutic schemes reduced the percentage of positive blood cultures in both isogenic groups (P<0.05). Finally, the survival results suggest a higher mortality with the strains expressing qnr genes.
  
  
  CONCLUSIONS
  The presence of qnrA1, qnrB1 and qnrS1 in E. coli reduced the efficacy of ciprofloxacin and levofloxacin in a murine pneumonia model.
authors.affiliation: Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. judoher@yahoo.es
authors.forename: J
authors.initials: J
authors.lastname: Domínguez-Herrera
authors.forename: C
authors.initials: C
authors.lastname: Velasco
authors.forename: F
authors.initials: F
authors.lastname: Docobo-Pérez
authors.forename: J M
authors.initials: JM
authors.lastname: Rodríguez-Martínez
authors.forename: R
authors.initials: R
authors.lastname: López-Rojas
authors.forename: A
authors.initials: A
authors.lastname: Briales
authors.forename: C
authors.initials: C
authors.lastname: Pichardo
authors.forename: P
authors.initials: P
authors.lastname: Díaz-de-Alba
authors.forename: J
authors.initials: J
authors.lastname: Rodríguez-Baño
authors.forename: A
authors.initials: A
authors.lastname: Pascual
authors.forename: J
authors.initials: J
authors.lastname: Pachón
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002939:Ciprofloxacin / Q000008:administration & dosage*; D027081:DNA Gyrase / Q000235:genetics; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics*; D005260:Female; D064704:Levofloxacin / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D050505:Mutant Proteins / Q000235:genetics; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D050505:Mutant Proteins; C485384:Qnr protein, E coli; D002939:Ciprofloxacin; D064704:Levofloxacin; D027081:DNA Gyrase
keywords: Enterobacteriaceae; mouse model; pharmacodynamics; pharmacokinetics