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  • Title: Comparison of the bactericidal activities and post-antibiotic effects of the Des-F(6)-quinolone BMS-284756, levofloxacin, and ciprofloxacin against methicillin-susceptible and methicillin-resistant Staphylococcus aureus.
    Author: Ryan BM, Mazzucco CE, Lawrence LE, Ho H, Warr G, Barrett JF, Frosco M.
    Journal: Eur J Clin Microbiol Infect Dis; 2002 Jan; 21(1):27-34. PubMed ID: 11913498.
    Abstract:
    The bactericidal activities and post-antibiotic effects of BMS-284756 (T-3811ME), levofloxacin, and ciprofloxacin were evaluated against a methicillin-susceptible and a methicillin-resistant Staphylococcus aureus strain. Minimum inhibitory concentrations (MICs), minimum bactericidal concentrations, post-antibiotic effects, and post-antibiotic sub-MIC effects were determined and time-kill studies were performed for BMS-284756, levofloxacin, and ciprofloxacin. At 4-times and 10-times the MIC, time-kill kinetics over 3 h and over 24 h were similar for all three quinolones when effects were considered as multiples of the MIC. All three quinolones achieved a 3 log10 reduction in cfu/ml within 2 h. At 10-times the MIC, the post-antibiotic effects of BMS-284756, levofloxacin, and ciprofloxacin were 1.6-2.6 h for the methicillin-susceptible Staphylococcus aureus strain and 1.5-1.9 h for the methicillin-resistant Staphylococcus aureus strain. When actual concentrations were considered, BMS-284756 achieved results comparable to levofloxacin and ciprofloxacin at concentrations nearly 10-fold less. When relating the pharmacokinetic properties of the three quinolones to their in vitro activities, the resulting Cmax/MIC and AUC/MIC ratios were. respectively, 120-240.7 and 1,321.7-2,643 for BMS-284756, 22.8 and 190 for levofloxacin, and 5.9-11.9 and 54.8-109.6 for ciprofloxacin. The greater in vitro activity and favorable human pharmacokinetics of BMS-284756 may translate to improved clinical effectiveness of this agent compared to currently marketed quinolones.
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