Comparative mutant prevention concentration and mechanism of resistance to veterinary fluoroquinolones in Staphylococcus pseudintermedius.

摘要: Background –  The problem of antibacterial drug resistance is increasing worldwide, in part due to the therapeutic concentrations currently used based on minimal inhibitory concentration (MIC) as a measure potency are often very required selectively enrich resistant mutant portion population. A prevention (MPC)-based dosing strategy suggested improve outcome MIC. Objective –  Our aim was investigate MPC and mechanism various fluoroquinolones using recent Staphylococcus pseudintermedius isolates from canine pyoderma. Methods –  broth microdilution method for MIC series agar plates containing different were inoculated with ∼1010 colony-forming units bacterial culture used. PCR identify mutation isolates. Results –  rank order ciprofloxacin = enrofloxacin ≥ marbofloxacin > difloxacin ≥ orbifloxacin. Integrating our data reported pharmacokinetic at recommended dose ranges revealed that only high doses ciprofloxacin, enrofloxacin marbofloxacin could achieve maximal plasma (Cmax) greater than 90% (Cmax/MPC90). overall against S. pseudintermedius, Cmax/MIC, Cmax/MPC, area under concentration–time curve (AUC)/MIC AUC/MPC values, decreasing order: enrofloxacin > ciprofloxacin ≥ marbofloxacin ≥ orbifloxacin = difloxacin. Sequencing quinolone determining region gyrA, gyrB, grlA grlB strains showed base-pair substitution both gyrA gyrB resulted Ser-84 Leu Ser-80 Arg amino acid changes, respectively. Conclusions clinical importance –  High minimize selection mutants, whereas possibility selecting mutants conventional difloxacin orbifloxacin, low all fluoroquinolones, seems high.