title: Comparative mutant prevention concentrations of pradofloxacin and other veterinary fluoroquinolones indicate differing potentials in preventing selection of resistance.
abstract: Pradofloxacin (PRA) is an 8-cyano-fluoroquinolone (FQ) being developed to treat bacterial infections in dogs and cats. Its mutant prevention concentrations (MPC) were determined for Escherichia coli ATCC 8739 at 0.225 microg/ml, and for Staphylococcus aureus ATCC 6538 at 0.55 microg/ml. At drug concentrations equal to or above the MPC, growth (implying selective clonal expansion) of first-step FQ-resistant variants, naturally present in large bacterial populations, was inhibited. MPC(90) derived from 10 clinical isolates each of E. coli and Staphylococcus intermedius, the latter species being of greater clinical relevance than S. aureus in companion-animal medicine, amounted to 0.2 to 0.225 and 0.30 to 0.35 microg/ml, respectively. MPCs of other veterinary FQs were assessed to determine relative in vitro potencies. The MPCs of marbofloxacin, enrofloxacin, danofloxacin, sarafloxacin, orbifloxacin, and difloxacin were 1.2-, 1.4-, 2.3-, 2.4-, 5-, and 7-fold higher than the MPC of PRA for E. coli ATCC 8739, and 6-, 6-, 19-, 15-, 15-, and 31-fold higher than the MPC of PRA for S. aureus ATCC 6538, respectively. MPC curves revealed a pronounced heterogeneity in susceptibility within populations of > or =4 x 10(9) CFU employed, extending to 10-fold above the MICs. The duration of incubation and, for S. aureus, inoculum density profoundly affected the MPCs. With appropriate dosing, PRA may combine high therapeutic efficacy with a high potential for restricting the selection for FQ resistance under field conditions in the species analyzed.
authors.affiliation: Bayer HealthCare AG, Animal Health Division, Leverkusen, Germany. heinz-georg.wetzstein@bayerhealthcare.com
authors.forename: H-G
authors.initials: HG
authors.lastname: Wetzstein
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002415:Cats; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D024841:Fluoroquinolones / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000187:drug effects*; D012641:Selection, Genetic; D013210:Staphylococcus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; C507250:pradofloxacin