Mutant Prevention Concentrations of Fluoroquinolones for Clinical Isolates of Streptococcus pneumoniae

Abstract

ABSTRACT The mutant prevention concentration (MPC) represents a threshold above which the selective proliferation of resistant mutants is expected to occur only rarely. A provisional MPC (MPC pr ) was defined and measured for five fluoroquinolones with clinical isolates of Streptococcus pneumoniae . Based on their potential for restricting the selection of resistant mutants, the five fluoroquinolones, in descending order, were found to be moxifloxacin > trovafloxacin > gatifloxacin > grepafloxacin > levofloxacin. For several compounds, 90% of about 90 clinical isolates that lacked a known resistance mutation had a value of MPC pr that was close to or below the serum levels that could be attained with a dosing regimen recommended by the manufacturers. Since MPC pr overestimates MPC, these data identify moxifloxacin and gatifloxacin as good candidates for determining whether MPC pr can be used as a guide for choosing and eventually administering fluoroquinolones to significantly reduce the development of resistance.