Comparative pharmacodynamics of garenoxacin, gemifloxacin, and moxifloxacin in community-acquired pneumonia caused by Streptococcus pneumoniae: a Monte Carlo simulation analysis

Clinical Therapeutics
Ayman M NoreddinG G Zhanel

Abstract

This study used Monte Carlo simulations to assess the potential for attainment of pharmacodynamic 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). Data on the free AUC over 24 hours (fAUC(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 Susceptibility Study. These data were used to produce the ratio of fAUC(0-24) to the MIC(90) (fAUC(0-24)/MIC(90)), a pharmacodynamic 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 fAUC(0-24)/MIC(90) ratios of 30, 40, 100, and 120 against S pneumoniae in serum and ELF from hospitalized patients 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 probability of preventing development of resis...Continue Reading

Citations

Nov 4, 2009·Antimicrobial Agents and Chemotherapy·David T ChungMing-Chu Hsu
Mar 9, 2010·International Journal of Antimicrobial Agents·Yoshinobu OhsakiSatoru Fujiuchi
Dec 15, 2015·Therapeutic Advances in Respiratory Disease·Fumitaka ItoShinya Minatoguchi
Dec 14, 2018·Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer·Masaya TakahashiKatsuya Nagayama
Nov 16, 2010·Expert Review of Anti-infective Therapy·Brian Wispelwey, Katherine R Schafer
Mar 12, 2013·Expert Review of Clinical Pharmacology·Ashit TrivediBernd Meibohm

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