Bacterial strain-independent AUC/MIC and strain-specific dose-response relationships reflecting comparative fluoroquinolone anti-pseudomonal pharmacodynamics in an in vitro dynamic model.

To compare the antimicrobial effects (AMEs) of two quinolones in terms of the AUC/MIC- and dose (D)-response relationships, five differentially susceptible clinical isolates of Pseudomonas aeruginosa were exposed to decreasing concentrations of ciprofloxacin (two 12-h doses with T(1/2) = 4 h) and trovafloxacin (a single dose with T(1/2) = 9.2 h). The simulated AUC/MICs of ciprofloxacin ranged from 58 to 932 and those of trovafloxacin, from 54 to 466 h. The intensity of the AME (I(E)) correlated well with log AUC/MIC for both ciprofloxacin and trovafloxacin (r(2) = 0.99 and 0.97, respectively) in a strain-independent fashion. At a given AUC/MIC ratio, AMEs of trovafloxacin were greater than ciprofloxacin. However, based on the respective I(E)-logD curves, 200 mg trovafloxacin produced a slightly greater AME than 2 x 500 mg ciprofloxacin only with the most susceptible P. aeruginosa. With the less susceptible P. aeruginosa ciprofloxacin was more efficient than trovafloxacin. This study suggests that both bacterial strain-independent AUC/MIC- and the respective strain-specific dose-response relationships of the AME are important for comprehensive pharmacodynamic evaluation of antimicrobial agents.