Impact of short-course quinolone therapy on susceptible and resistant populations of Staphylococcus aureus.

Abstract

We previously demonstrated that therapy duration has a differential impact on susceptible and resistant subpopulations of Staphylococcus aureus. What our previous investigation did not address was what would transpire after stopping therapy and whether these events would be different in susceptible and resistant subpopulations. We used the regimen previously demonstrated to amplify resistant subpopulation at day 4-5 (area under the concentration-time curve/minimum inhibitory concentration ratio, 100). Therapy was started in our hollow-fiber infection model on day 0; garenoxacin was administered in 4, 5, or 6 doses (days 3-5). The system was observed until day 13. Four drug doses kept the susceptible population dominant, but with the resistant subpopulation amplifying. Five and 6 doses caused the resistant population to exceed the susceptible population at the end of therapy and for a variable time thereafter. Ultimately, the susceptible population became dominant by day 13. Modeling demonstrated that the resistant isolates grew more slowly and had a higher natural death rate.