The relationship between quinolone exposures and resistance amplification is characterized by an inverted U: a new paradigm for optimizing pharmacodynamics to counterselect resistance.
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.
Tam
Vincent H
VH
Emerging Infections and Host Defense Laboratory, Ordway Research Institute, Albany, NY, USA. vtam@uh.edu
Louie
Arnold
A
Deziel
Mark R
MR
Liu
Weiguo
W
Drusano
George L
GL
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
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D011804:Quinolines; C037219:quinoline; C419689:garenoxacin