title: The relationship between quinolone exposures and resistance amplification is characterized by an inverted U: a new paradigm for optimizing pharmacodynamics to counterselect resistance.
abstract: We determined the relationship between garenoxacin exposure and quinolone-resistant subpopulations for three bacterial isolates in an in vitro hollow-fiber infection model. An "inverted-U" relationship was identified wherein resistant subpopulations rose initially and then declined with increasing exposure, until reaching a threshold that prevented resistance amplifications. Different targets for the area under the concentration-time curve over 24 h/MIC ratio were required for different bacteria.
authors.affiliation: Emerging Infections and Host Defense Laboratory, Ordway Research Institute, Albany, NY, USA. vtam@uh.edu
authors.forename: Vincent H
authors.initials: VH
authors.lastname: Tam
authors.forename: Arnold
authors.initials: A
authors.lastname: Louie
authors.forename: Mark R
authors.initials: MR
authors.lastname: Deziel
authors.forename: Weiguo
authors.initials: W
authors.lastname: Liu
authors.forename: George L
authors.initials: GL
authors.lastname: Drusano
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D024841:Fluoroquinolones / Q000378:metabolism / Q000494:pharmacology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D011804:Quinolines / Q000378:metabolism / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D011804:Quinolines; C037219:quinoline; C419689:garenoxacin