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.
Department of Pharmacokinetics and Pharmacodynamics, Gause Institute of New Antibiotics, 11 Bolshaya Pirogovskaya Street, Moscow 119992, Russia.
Irene Yu
IY
Lubenko
Sergey N
SN
Vostrov
Yury A
YA
Portnoy
Stephen H
SH
Zinner
Alexander A
AA
Firsov
D000890:Anti-Infective Agents / Q000494:pharmacology*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009287:Naphthyridines / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D002939:Ciprofloxacin; C080163:trovafloxacin