In the early 1990s, soon after ciprofloxacin entered the market, it was used for S. pneumoniae. It did not work very well, and it was withdrawn from this indication. In retrospect we can understand why it did not do well. When you plot the ciprofloxacin pharmacokinetic curve relative to MIC and MPC, you see that ciprofloxacin concentration barely exceeds the MIC (filled circles). Levofloxacin, however, (open circles), climbs much higher relative to the MIC, and so it is expected to give a better cure rate. Indeed, it is considered to be quite effective. However, you will notice that levofloxacin is inside the selection window throughout therapy. Thus we predicted (14) that widespread resistance to levofloxacin would arise.

The question of which compound would selectively enrich mutants more rapidly is complex because non-topoisomerase mutants tend to be recovered in great numbers when drug concentrations are near the MIC. When drug concentrations are higher in the window, the abundant non-topoisomerase mutants are not recovered. Moreover, the higher concentrations tend to more effectively eliminate susceptible cells, thereby elevating the chance that host defenses will remove resistant mutants. It is not likely to be helpful for ciprofloxacin concentration to drop well below the MIC where selective pressuure is weak because susceptible cell outgrowth will occur.