Pharmacodynamics of ibafloxacin in micro-organisms isolated from cats.
The pharmacodynamic properties of ibafloxacin were investigated in micro-organisms isolated from cats. Minimal inhibitory concentrations (MIC) of ibafloxacin (racemate, R- and S-enantiomers) and its metabolites (7-hydroxy- and 8-hydroxy-ibafloxacin) and time-kill kinetics were determined against Gram-negative and Gram-positive bacteria isolated from dermal and respiratory and urinary tract infections in cats. Racemic ibafloxacin has a broad spectrum of bactericidal activity against Gram-negative and some Gram-positive bacteria. Escherichia coli and Pasteurella, Klebsiella and Staphylococcus spp. are commonly isolated from feline infections and all are susceptible to ibafloxacin (MIC90 < or = 0.5 microg/mL), whereas Pseudomonas aeruginosa, Proteus mirabilis and Streptococcus spp. are considered intrinsic resistant. Microbiological activity resides primarily in the S-enantiomer of ibafloxacin whereas the R-enantiomer is less active. Killing curves using concentrations of racemic ibafloxacin and 8-hydroxy-ibafloxacin, which are representative of the in vivo situation observed in cats, showed at least 99.9% reduction in viable bacterial isolates from feline clinical samples over 24 h. Bacterial eradication was achieved in cats with Cmax/MIC and AUC/MIC values much lower than the target values previously established in man and laboratory animals. Additional studies in dogs and cats are necessary to define more clearly the surrogate markers of antibacterial activity (i.e. Cmax/MIC, AUC/MIC ratios), which are associated with a good clinical response.
Coulet
M
M
Intervet Pharma R&D S.A., Angers Technopole, Rue Olivier de Serres, Beaucouzé Cedex, France. myriam.coulet@intervet.com
Cox
P
P
Lohuis
J
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002371:Cat Diseases / Q000382:microbiology*; D002415:Cats; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011807:Quinolizines / Q000493:pharmacokinetics / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D011807:Quinolizines; C049886:ibafloxacin