Prediction of the antimicrobial effects of trovafloxacin and ciprofloxacinon staphylococci using an in-vitro dynamic model

To compare the pharmacodynamics of trovafloxacin and ciprofloxacin, three c linical isolates of Staphylococcus aureus with different MICs (0.03, 0.15, 0.6 and 0.1, 0.25, 1.25 mg/L, respectively) were exposed to decreasing conc entrations of the quinolones according to their half-lives of 9.25 and 4 h, respectively. With each organism, single doses of trovafloxacin and twice- daily doses of ciprofloxacin were designed to provide 8-fold ranges of the ratio of area under the concentration-time curve (AUC) to the MIC, 58-466 a nd 116-932 (mg.h/L)/(mg/L), respectively. The antimicrobial effect was expr essed by its intensity: the area between the control growth in the absence of antibiotics and the antibiotic-induced time-kill/regrowth curves (I-E). Linear relationships established between I-E and log AUC/MIC were bacterial strain-independent but specific for the quinolones (r(2) = 0.99 in both ca ses). At a given AUC/MIC ratio, the I(E)s of trovafloxacin were greater tha n those of ciprofloxacin, suggesting that the antimicrobial effect of trova floxacin compared with ciprofloxacin against staphylococci may be even grea ter than might be expected from the difference in their MICs. These data we re combined with previous results obtained with three Gram-negative bacteri a. Again, I-E correlated well with the log AUC/MIC of trovafloxacin and cip rofloxacin in a strain- and species-independent fashion (r(2) = 0.94 and 0. 96, respectively). On this basis, a value of the AUC/MIC of trovafloxacin w hich might be equivalent to Schentag's AUC/MIC = 125 (mg.h/L)/(mg/L) report ed as the breakpoint value for ciprofloxacin was estimated at 71 (mg.h/L)/( mg/L) with the respective MIC breakpoint of 0.27 mg/L. Based on the I-E-log AUC/MIC relationships, the I(E)s were plotted against the logarithm of tro vafloxacin and ciprofloxacin dose (D) for hypothetical representatives of S . aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginos a with MICs corresponding to the MIC(50)s. These I-E-log D relationships al low prediction of the effect of a given quinolone on a representative strai n of the bacterial species.