Comparison of pharmacodynamic and pharmacokinetic indices of efficacy for 5 fluoroquinolones toward pathogens of dogs and cats.
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.
Boothe
Dawn Merton
DM
Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, 109 Greene Hall, Auburn, AL 36849, USA. boothdm@auburn.edu
Boeckh
Albert
A
Simpson
R Bruce
RB
Dubose
Kim
K
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
D000890:Anti-Infective Agents; D024841:Fluoroquinolones