Time-Kill Analysis of Canine Skin Pathogens: A Comparison of Pradofloxacin and Marbofloxacin

Stefano Azzariti (1) , Andrew Mead (1) , Pierre-Louis Toutain (1, 2) , Ross Bond (1) , Ludovic Pelligand (1)

1 Royal Veterinary College [London]
2 InTheRes - Innovations Thérapeutiques et Résistances

Time-kill curves (TKCs) are more informative compared with the use of minimum inhibitory concentration (MIC) as they allow the capture of bacterial growth and the development of drug killing rates over time, which allows to compute key pharmacodynamic (PD) parameters. Our study aimed, using a semi-mechanistic mathematical model, to estimate the best pharmacokinetic/pharmacodynamic (PK/PD) indices (ƒAUC/MIC or %ƒT > MIC) for the prediction of clinical efficacy of veterinary FQs in Staphylococcus pseudintermedius, Staphylococcus aureus, and Escherichia coli collected from canine pyoderma cases with a focus on the comparison between marbofloxacin and pradofloxacin. Eight TCKs for each bacterial species (4 susceptible and 4 resistant) were analysed in duplicate. The best PK/PD index was ƒAUC24h/MIC in both staphylococci and E. coli. For staphylococci, values of 25–40 h were necessary to achieve a bactericidal effect, whereas the calculated values (25–35 h) for E. coli were lower than those predicting a positive clinical outcome (100–120 h) in murine models. Pradofloxacin showed a higher potency (lower EC50) in comparison with marbofloxacin. However, no difference in terms of a maximal possible pharmacological killing rate (Emax) was observed. Taking into account in vivo exposure at the recommended dosage regimen (3 and 2 mg/kg for pradofloxacin and marbofloxacin, respectively), the overall killing rates (Kdrug) computed were also similar in most instances.

Mots clés: canine pyoderma Staphylococcus spp. Escherichia coli fluoroquinolones MIC mathematical modelling semi-mechanistic model PK/PD index dose fractionation resistance; canine pyoderma; Staphylococcus spp.; Escherichia coli; fluoroquinolones; MIC; mathematical modelling; semi-mechanistic model; PK/PD index; dose fractionation; resistance

Domaines: Pharmacologie

Stefano Azzariti, Andrew Mead, Pierre-Louis Toutain, Ross Bond, Ludovic Pelligand. Time-Kill Analysis of Canine Skin Pathogens: A Comparison of Pradofloxacin and Marbofloxacin. Antibiotics, 2023, 12 (10), pp.1548. ⟨10.3390/antibiotics12101548⟩. ⟨hal-04522061⟩