title: In vitro bactericidal activity of enrofloxacin against gyrA mutant and qnr-containing Escherichia coli isolates from animals.
abstract: The objective of this work was to investigate the bactericidal activity of enrofloxacin against gyrA mutant and qnr-containing Escherichia coli isolates from animals. The minimum inhibitory concentrations (MICs) of gyrA mutant and qnr-containing E coli isolates ranged from 1 µg/ml to 32 µg/ml for enrofloxacin. Time-kill experiments were performed using selected E coli isolates. For the time-kill experiments, the colony counts were determined by plating each diluted sample onto plate count agar and an integrated pharmacokinetic/pharmacodynamics area measure (log ratio area) was applied to the colony-forming units (cfu) data. In general, enrofloxacin exhibited bactericidal activity against all the gyrA mutant E coli isolates at all concentrations greater than four times the MIC. However, the bactericidal activity of enrofloxacin for all the qnr-containing E coli isolates was less dependent on concentration. The results of the present study indicated that the genetic mechanism of resistance might account for the different bactericidal activities of enrofloxacin observed for the gyrA mutant and the qnr-containing E coli isolates. Therefore, in addition to MIC assays, genetic mechanism-based pharmacodynamic models should be used to provide accurate predictions of the effects of drugs on resistant bacteria.
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Uludag University, Nilufer, Bursa 16059, Turkey. cengizm@uludag.edu.tr
authors.forename: M
authors.initials: M
authors.lastname: Cengiz
authors.forename: P
authors.initials: P
authors.lastname: Sahinturk
authors.forename: S
authors.initials: S
authors.lastname: Sonal
authors.forename: E
authors.initials: E
authors.lastname: Buyukcangaz
authors.forename: A
authors.initials: A
authors.lastname: Sen
authors.forename: E
authors.initials: E
authors.lastname: Arslan
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D015169:Colony Count, Microbial / Q000662:veterinary; D027081:DNA Gyrase / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial / Q000235:genetics; D000077422:Enrofloxacin; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones; C485384:Qnr protein, E coli; D000077422:Enrofloxacin; D027081:DNA Gyrase