title: Comparison of pharmacodynamic and pharmacokinetic indices of efficacy for 5 fluoroquinolones toward pathogens of dogs and cats.
abstract: BACKGROUND
  Fluoroquinolones are often used interchangeably in dogs and cats.
  
  
  OBJECTIVE
  Predicted therapeutic efficacy differs among fluoroquinolones.
  
  
  METHODS
  Bacterial pathogens isolated from dogs and cats.
  
  
  METHODS
  Using microtube-dilution procedures, percent resistance and 2 pharmacodynamic/pharmacokinetic indices (maximum concentration/minimum inhibitory concentration [Cmax/MIC] [target 0.10] and area under curve/minimum inhibitory concentration [AUC/MIC] [target 0.125]) were compared prospectively at low and high doses (mg/kg) for ciprofloxacin (5 and 20), difloxacin (5 and 10), enrofloxacin (including enrofloxacin+ciprofloxacin) (5 and 20), marbofloxacin (2.5 and 5), and orbifloxacin (2.5 and 7.5). Indices were calculated for organisms represented by < or = 15 isolates.
  
  
  RESULTS
  Percent resistance for all Gram-negative (n = 180; 20+/-3%; 39+/-5% for Escherichia coli) and Gram-positive isolates (n = 66; 18+/-3%) did not differ among drugs or organisms. The pattern of Cmax/MIC was generally enrofloxacin+ciprofloxacin > or = enrofloxacin or ciprofloxacin > or = marbofloxacin > or = orbifloxacin > or = difloxacin; and for AUIC/ MIC, enrofloxacin+ciprofloxacin > or = marbofloxacin > or = ciprofloxacin > or = enrofloxacin > difloxacin > orbifloxacin. Among susceptible Gram-negative isolates studied (n = 117), targeted Cmax/MIC or AUC/MIC were achieved in 88% of E. coli, 53% of Proteus mirabilis, and 35% of Pseudomonas aeruginosa; and for susceptible Gram-positive isolates studied (n = 49), 53% of Streptotoccus spp. and Staphylococcus intermedius and 27% of Staphylococcus spp. At the high dose, the proportion of isolates for which a target was reached was: ciprofloxacin, enrofloxacin+ciprofloaxin, and marbofloxacin (77%), enrofloxacin (73%), orbifloxacin (51%), and difloxacin (40%); and at the low dose, enrofloxacin+ciprofloxacin and enrofloxacin (43%), ciprofloxacin (40%), marbofloxacin (39%), orbifloxacin (29%), and difloxacin (28%).
  
  
  CONCLUSIONS
  E. coli resistance to fluoroquinolones approximated 40%. For susceptible isolates, enrofloxacin, marbofloxacin, and ciprofloxacin more consistently reached indices associated with predicted efficacy, but only at the high dose.
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, 109 Greene Hall, Auburn, AL 36849, USA. boothdm@auburn.edu
authors.forename: Dawn Merton
authors.initials: DM
authors.lastname: Boothe
authors.forename: Albert
authors.initials: A
authors.lastname: Boeckh
authors.forename: R Bruce
authors.initials: RB
authors.lastname: Simpson
authors.forename: Kim
authors.initials: K
authors.lastname: Dubose
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use; D019540:Area Under Curve; D002371:Cat Diseases / Q000188:drug therapy* / Q000382:microbiology; D002415:Cats; D015169:Colony Count, Microbial / Q000662:veterinary; D004283:Dog Diseases / Q000188:drug therapy* / Q000382:microbiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones