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Several new quinolones that exhibit enhanced in vitro activity against Streptococcus pneumoniae have been developed. Using a dynamic in vitro model, we generated time-kill data for ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin against three isolates of quinolone-susceptible S. pneumoniae. Three pharmacokinetic profiles were simulated for each of the study agents (0.1, 1, and 10 times the area under the concentration-time curve [AUC]). Target 24-h AUCs were based upon human pharmacokinetic data resulting from the maximal daily doses of each agent. Ciprofloxacin was the least active agent against all three isolates. With regimens that simulated the human 24-h AUC, ciprofloxacin resulted in an initial, modest decline in the numbers of CFU per milliliter; however, by 48 h the numbers of CFU per milliliter returned to or exceeded the starting inoculum. At the AUC, levofloxacin resulted in variable bacteriostatic and bactericidal activities against the isolates. The remaining agents yielded bactericidal (99.9% reduction) activity by 48 h with regimens that simulated the AUC. At 0.1 time the AUC ciprofloxacin and levofloxacin produced no inhibitory effect, grepafloxacin exhibited bacteriostatic activity, trovafloxacin had mixed static and cidal activities, and clinafloxacin and moxifloxacin caused significant reductions in the numbers of CFU per milliliter by 48 h. All six agents produced cidal activity at 10 times the AUC. In this dynamic in vitro model of infection, the quinolones demonstrated various degrees of activity against S. pneumoniae. The rank order of activity, with respect to bactericidal effect, was ciprofloxacin (least active) &lt;&lt; levofloxacin &lt; grepafloxacin, trovafloxacin &lt; clinafloxacin and moxifloxacin (most active). The rank order of the agents with respect to the selection of resistance was ciprofloxacin (most likely) &gt; grepafloxacin, moxifloxacin, and trovafloxacin &gt; levofloxacin &gt; clinafloxacin.

antimicrobial agents and chemotherapy

Comparative Bactericidal Activities of Ciprofloxacin, Clinafloxacin, Grepafloxacin, Levofloxacin, Moxifloxacin, and Trovafloxacin against <i>Streptococcus pneumoniae</i> in a Dynamic In Vitro Model

Comparative Bactericidal Activities of Ciprofloxacin, Clinafloxacin, Grepafloxacin, Levofloxacin, Moxifloxacin, and Trovafloxacin against Streptococcus pneumoniae in a Dynamic In Vitro Model