title: Evaluation of the effect of bacterial efflux pumps on the antibacterial activity of the novel fluoroquinolone besifloxacin.
abstract: This study examined the susceptibility of a variety of wild-type strains and efflux pump mutants to besifloxacin and the comparator agents sparfloxacin, ciprofloxacin, norfloxacin, moxifloxacin, tetracycline, and ethidium bromide. Organisms tested included Staphylococcus aureus (mepA or norA), Streptococcus pneumoniae (pmrA, patB), Escherichia coli (acrAB::Tn903, tolC::Tn10), Haemophilus influenzae (acrAB) and Pseudomonas aeruginosa (mepAB-oprM, oprM::ΩHg(r) rpsL). The minimal inhibitory concentrations (MIC) of besifloxacin and comparators were also measured in the presence of the efflux pump inhibitors reserpine, carbonyl cyanide mchlorophenyl- hydrazone, or sodium orthovanadate. Overall, very few meaningful changes (>2-fold) in besifloxacin MIC values resulted from the presence of efflux pump mutations or efflux pump inhibitors. In summary, the novel fluoroquinolone besifloxacin is no exception to the observation that newer fluoroquinolones are generally less affected by efflux pump-mediated resistance than older fluoroquinolones.
authors.affiliation: Micromyx LLC, 4717 Campus Drive, Kalamazoo, Michigan, USA. DLShinabarger@micromyx.com
authors.forename: D L
authors.initials: DL
authors.lastname: Shinabarger
authors.forename: G E
authors.initials: GE
authors.lastname: Zurenko
authors.forename: C K
authors.initials: CK
authors.lastname: Hesje
authors.forename: C M
authors.initials: CM
authors.lastname: Sanfilippo
authors.forename: T W
authors.initials: TW
authors.lastname: Morris
authors.forename: W
authors.initials: W
authors.lastname: Haas
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000378:metabolism; D004347:Drug Interactions; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D026901:Membrane Transport Proteins / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D016254:Mutagenesis, Insertional / Q000235:genetics / Q000502:physiology; D009154:Mutation; D000091243:Ribosomal Protein S9; D014475:Uncoupling Agents / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001381:Azepines; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones; D026901:Membrane Transport Proteins; D000091243:Ribosomal Protein S9; C000717190:RpsI protein, E coli; D014475:Uncoupling Agents; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; C522124:besifloxacin