In vitro and in vivo pharmacodynamic properties of the fluoroquinolone ibafloxacin

The pharmacodynamic properties of a new veterinary fluoroquinolone antimicrobial agent, ibafloxacin, were evaluated. Minimal inhibitory concentrations (MIC), time‐kill kinetics, postantibiotic effect (PAE) and postantibiotic subminimal inhibitory concentration effects (PA‐SME) were determined agains...

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Bibliographic Details
Published in:Journal of veterinary pharmacology and therapeutics 2002-12, Vol.25 (6), p.401-411
Main Authors: Coulet, M., Van Borssum Waalkes, M., Cox, P., Lohuis, J.
Format: Article
Language:English
Subjects:
Animals
Anti-Infective Agents - pharmacology
Anti-Infective Agents - therapeutic use
Cystitis - drug therapy
Dogs
Female
Fluoroquinolones
Male
Microbial Sensitivity Tests
Quinolizines - pharmacology
Quinolizines - therapeutic use
Wound Infection - drug therapy
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Summary:The pharmacodynamic properties of a new veterinary fluoroquinolone antimicrobial agent, ibafloxacin, were evaluated. Minimal inhibitory concentrations (MIC), time‐kill kinetics, postantibiotic effect (PAE) and postantibiotic subminimal inhibitory concentration effects (PA‐SME) were determined against pathogenic canine Gram‐negative and Gram‐positive bacterial isolates from dermal, respiratory and urinary tract infections. The synergistic interactions between ibafloxacin and its main metabolite, 8‐hydroxy‐ibafloxacin were investigated. Finally, the efficacy of ibafloxacin was tested in in vivo canine infection models. Ibafloxacin had good activity against Pasteurella spp., Escherichia coli, Klebsiella spp., Proteus spp. and Staphylococcus spp. (MIC90=0.5 µg/mL), moderate activity against Bordetella bronchiseptica, Enterobacter spp. and Enterococcus spp. (MIC50=4 µg/mL) and low activity against Pseudomonas spp. and Streptococcus spp. The time‐killing analysis confirmed that ibafloxacin was bactericidal with a broad spectrum of activity. The PAE and PA‐SME were between 0.7–2.13 and 1–11.5 h, respectively. Finally, studies in dog models of wound infection and cystitis confirmed the efficacy of once daily oral ibafloxacin at a dosage of 15 mg/kg. Additional studies are needed to better define the importance of AUC/MIC (AUIC) and Cmax/MIC ratios on the outcome of fluoroquinolone therapy in dogs.
ISSN:0140-7783
1365-2885
DOI:10.1046/j.1365-2885.2002.00438.x