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

• Main Authors: Stefano Azzariti (Author), Andrew Mead (Author), Pierre-Louis Toutain (Author), Ross Bond (Author), Ludovic Pelligand (Author)
• Format: Book
• Published: MDPI AG, 2023-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 <i>Staphylococcus pseudintermedius</i>, <i>Staphylococcus aureus</i>, and <i>Escherichia coli</i> 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 ƒAUC_24h/MIC in both staphylococci and <i>E. coli</i>. For staphylococci, values of 25-40 h were necessary to achieve a bactericidal effect, whereas the calculated values (25-35 h) for <i>E. coli</i> 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 (E_max) 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 (K_drug) computed were also similar in most instances.

Item Description

10.3390/antibiotics12101548
2079-6382