ABSTRACT Objective: This study used Monte Carlo simulations to assess the potential for attainment of pharmacody- namic targets with the fluoroquinolones garenoxacin, gemifloxacin, and moxifloxacin against Streptococcus pneumoniae in serum and epithelial lining fluid (ELF) from hospitalized patients with community-acquired pneumonia (CAP). Methods: Data on the free AUC over 24 hours (ƒAUC 0–24 ), a measure of drug exposure, were derived from previously described population pharmacokinetic models for therapeutic doses of the 3 fluoroquinolones. MIC distribution data for S pneumoniae were obtained from the Canadian Respiratory Organism Suscep- tibility Study. These data were used to produce the ratio of ƒAUC 0–24 to the MIC 90 (ƒAUC 0–24 /MIC 90 ), a phar- macodynamic predictor of bacterial eradication. Monte Carlo simulations were used to analyze the potential for garenoxacin 400 mg QD, gemifloxacin 320 mg QD, and moxifloxacin 400 mg QD to achieve target ƒAUC 0–24 /MIC 90 ratios of 30, 40, 100, and 120 against S pneumoniae in serum and ELF from hospitalized pa- tients with CAP. Target ratios of 30 and 40 were used to assess the probability of bacterial eradication, while ratios of 100 and 120 were used to assess the probabili- ty of preventing development of resistance. Results: Monte Carlo simulations indicated that all 3 fluoroquinolones had a high probability (>90%) of attaining target ƒAUC 0–24 /MIC 90 ratios of 30 and 40 against S pneumoniae in both serum and ELF. Garen- oxacin 400 mg QD was associated with a >95% prob- ability of achieving target ƒAUC 0–24 /MIC 90 ratios of 100 and 120 in both serum and ELF. Both gemifloxacin 320 mg QD and moxifloxacin 400 mg QD were asso- ciated with high probabilities of attaining ƒAUC 0–24 / MIC 90 ratios of 100 and 120 in ELF (>95%); the prob- ability of gemifloxacin and moxifloxacin attaining these targets in serum ranged from 78.3% to 88.0%. Conclusion: Based on these simulations, garenoxacin 400 mg QD, gemifloxacin 320 mg QD, and moxi- floxacin 400 mg QD appeared likely to achieve target serum and ELF concentrations against S pneumoniae in hospitalized patients with CAP, with a low potential to select for resistance. (Clin Ther. 2007;29:2685–2689) Copyright © 2007 Excerpta Medica, Inc. Key words: target attainment, fluoroquinolones, community-acquired pneumonia, Monte Carlo analysis. INTRODUCTION Community-acquired pneumonia (CAP) is a common respiratory illness that is frequently life threatening in the elderly. 1 CAP is a significant cause of both mor- bidity and mortality worldwide. 1 Streptococcus pneu- moniae accounts for 9% to 55% of cases of CAP requiring hospitalization 1–5 and is the most common cause of fatal CAP. 6 Treatment of lower respiratory infections, particularly CAP, commonly includes the use of the newer respiratory fluoroquinolones. 7 Several authorities, including the Infectious Diseases December 2007 2685 Comparative Pharmacodynamics of Garenoxacin, Gemifloxacin, and Moxifloxacin in Community-Acquired Pneumonia Caused by Streptococcus pneumoniae: A Monte Carlo Simulation Analysis Ayman M. Noreddin, PhD 1,2 ; Angela A. Reese, PharmD 1 ; Melissa Ostroski, PharmD 1 ; Daryl J. Hoban PhD 2,3 ; and George G. Zhanel, PharmD, PhD 2,3 1 Department of Pharmacy Practice and Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Duluth, Minnesota; 2 Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada; and 3 Department of Clinical Microbiology, Health Sciences Centre, Winnipeg, Canada Accepted for publication October 2, 2007. doi:10.1016/j.clinthera.2007.12.019 0149-2918/$32.00 Printed in the USA. Reproduction in whole or part is not permitted. Copyright © 2007 Excerpta Medica, Inc.