Activities of trovafloxacin, gatifloxacin, clinafloxacin, sparfloxacin, levofloxacin, and ciprofloxacin against penicillin-resistant Streptococcus pneumoniae in an in vitro infection model

We adapted an in vitro pharmacodynamic model of infection to incorporate in fected fibrin clots. The bactericidal activities of various fluoroquinolone s against two strains of penicillin-resistant Streptococcus pneumoniae were studied over a 48-h period. Bacteria were prepared in Muller-Hinton broth by using colonies from a 24-h tryptic soy agar plus 5% sheep blood plate an d were added to a mixture of cryoprecipitate (80%) and thrombin (10%) to ac hieve approximately 10(6) CFU of organism per fibrin clot. The fibrin clots were suspended into the models and removed, in triplicate, at various time points over 48 h, Control models were also conducted to characterize the g rowth of S, pneumoniae in the growth medium without antibiotic. Trovafloxac in, gatifloxacin, clinafloxacin, sparfloxacin, levofloxacin, and ciprofloxa cin were administered to simulate their pharmacokinetic profiles in humans. Fibrin clot samples were also plated onto antibiotic-containing tryptic so y agar plus 5% lysed horse blood to detect resistance. The newer fluoroquin olones demonstrated better activity than ciprofloxacin against both isolate s. In conclusion, the newer quinolones demonstrated significant activity ag ainst penicillin-resistant S. pneumoniae, with standard dosing resulting in area under the concentration-time curve/MIC ratios and peak concentration/ MIC ratios that resulted in 99.9% killing against these isolates.