Mutant-prevention concentration and mechanism of resistance in clinical isolates and enrofloxacin/marbofloxacin-selected mutants of Escherichia coli of canine origin

• DOI: 10.1099/jmm.0.028654-0
• Publication Date: 2011-05-20T02:51:29Z
• Authors: Elias Gebru; Myung-Jin Choi; Seung-Jin Lee; Dereje Damte; Seung Chun Park
• Keywords: DNA, Bacterial; Male; 0301 basic medicine; Enrofloxacin; Time Factors; Molecular Sequence Data; Microbial Sensitivity Tests; Sequence Analysis, DNA; Anti-Bacterial Agents; 3. Good health; 03 medical and health sciences; Dogs; Drug Resistance, Bacterial; Mutation; Escherichia coli; Animals; Female; Dog Diseases; Selection, Genetic; Escherichia coli Infections; Fluoroquinolones

The antibacterial activity and selection of resistant bacteria, along with mechanisms fluoroquinolone resistance, were investigated by integrating the static [MIC or mutant-prevention concentration (MPC)] in vitro dynamic model approaches using Escherichia coli isolates from diseased dogs. Using models, selected E. strains enrofloxacin marbofloxacin at a range simulated area under concentration-time curve over 24 h interval (AUC(24 h))/MIC ratios investigated. Our results indicated increasing losses susceptibility upon continuous exposure to vitro. This effect was transferable other fluoroquinolones, as well structurally unrelated drugs. also confirmed an AUC(24 h)/MIC h)/MPC)-dependent mutants, which maximum occurred 40-60. h)/MPC 39 (enrofloxacin) 32 (marbofloxacin) considered protective against mutants coli. Integrating our MIC MPC data published pharmacokinetic information dogs revealed better conventional dosing regimen than that restricting Target mutations, especially codon 83 (serine leucine) gyrA, overexpression efflux pumps contributed resistance development both clinically vitro-selected We report here previously undescribed mutation 116 parC two laboratory-derived Additional studies would determine exact role this susceptibility, establish importance findings clinical setting.