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

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-m...

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Bibliographic Details
Published in:Antibiotics (Basel) 2023-10, Vol.12 (10), p.1548
Main Authors: Azzariti, Stefano, Mead, Andrew, Toutain, Pierre-Louis, Bond, Ross, Pelligand, Ludovic
Format: Article
Language:English
Subjects:
Analysis
Animal models
Antibiotics
canine pyoderma
Drug dosages
E coli
Escherichia coli
Estimates
fluoroquinolones
Life Sciences
mathematical modelling
Mathematical models
Methicillin
MIC
Minimum inhibitory concentration
Pathogens
Pharmaceutical sciences
Pharmacodynamics
Pharmacokinetics
Pharmacology
Plasma
Pyoderma
Skin
Staphylococcus spp
Veterinary medicine
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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 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.
ISSN:2079-6382
2079-6382
DOI:10.3390/antibiotics12101548