Comparative activity of pradofloxacin and marbofloxacin against coagulase-positive staphylococci in a pharmacokinetic–pharmacodynamic model based on canine pharmacokinetics

Authors


Michael Kresken, PhD, Antiinfectives Intelligence GmbH, Campus of the University of Applied Sciences, 53359 Rheinbach, Germany. E-mail michael.kresken@antiinfectives-intelligence.de

Abstract

Körber-Irrgang, B., Wetzstein, H.-G., Bagel-Trah, S., Hafner, D., Kresken, M. Comparative activity of pradofloxacin and marbofloxacin against coagulase-positive staphylococci in a pharmacokinetic–pharmacodynamic model based on canine pharmacokinetics. J. vet. Pharmacol. Therap. 35, 571–579.

Pradofloxacin (PRA), a novel veterinary 8-cyano-fluoroquinolone (FQ), is active against Staphylococcus pseudintermedius, the primary cause of canine pyoderma. An in vitro pharmacokinetic–pharmacodynamic model was used to compare the activities of PRA and marbofloxacin (MAR) against three clinical isolates of S. pseudintermedius and reference strain Staphylococcus aureus ATCC 6538. Experiments were performed involving populations of 1010 CFU corresponding to an inoculum density of approximately 5 × 107 CFU/mL. The time course of free drug concentrations in canine serum was modelled, resulting from once daily standard oral dosing of 3 mg of PRA/kg and 2 mg of MAR/kg. In addition, experimentally high doses of 6 mg of PRA/kg and 16 mg of MAR/kg were tested against the least susceptible strain. Viable counts were monitored over 24 h. At concentrations associated with standard doses, PRA caused a faster and more sustained killing than MAR of all strains. The ratios of free drug under the concentration–time curve for 24 h over MIC and the maximum concentration of free drug over MIC were at least 90 and 26, and 8.5 and 2.1 for PRA and MAR, respectively. At experimentally high doses, PRA was superior to MAR in terms of immediate killing. Subpopulations with reduced susceptibility to either FQ did not emerge. We conclude that PRA is likely to be an efficacious therapy of canine staphylococcal infections.

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