Simulated comparison of the pharmacodynamics of ciprofloxacin and levofloxacin against Pseudomonas aeruginosa using pharmacokinetic data from healthy volunteers and 2002 minimum inhibitory concentration data
Abstract
Background: Until the 2002 approval of levofloxacin 750 mg QD, ciprofloxacin was the fluoroquinolone of choice against Pseudomonas aeruginosa infections.
Objective: This study evaluated the AUC:MIC ratios for ciprofloxacin 400 mg BID and TID and levofloxacin 750 mg QD, all administered intravenously, against P. aeruginosa using a Monte Carlo simulation.
Methods: Pharmacokinetic data for ciprofloxacin and levofloxacin and 2002 MIC distributions against P. aeruginosa were obtained from studies in healthy volunteers published in the peer-reviewed literature. Pharmacokinetic studies of each agent were identified by separate MEDLINE searches combining the MeSH heading pharmacokinetics with the generic name of the antimicrobial. Only human studies published in English between 1990 and 2001 were included. Included studies also had to meet 3 minimum criteria: evaluation of clinically relevant dosing regimens, use of rigorous study methods, and provision of mean (SD) values for the pharmacokinetic parameters of interest. When multiple studies met these criteria, a single study was selected for each antimicrobial regimen. Pharmacodynamic analysis was performed using a Monte Carlo simulation of 10,000 patients by integrating the pharmacokinetic parameters, their variability, and 2002 MIC distributions for each antimicrobial regimen. The probability of target attainment was determined for each regimen for an AUC:MIC ratio from 0 to 300. A > or =90% probability of target attainment was…
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