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.