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  • Title: Comparative activity of quinolones (ciprofloxacin, levofloxacin, moxifloxacin and garenoxacin) against extracellular and intracellular infection by Listeria monocytogenes and Staphylococcus aureus in J774 macrophages.
    Author: Seral C, Barcia-Macay M, Mingeot-Leclercq MP, Tulkens PM, Van Bambeke F.
    Journal: J Antimicrob Chemother; 2005 Apr; 55(4):511-7. PubMed ID: 15731197.
    Abstract:
    OBJECTIVES: Quinolones accumulate in eukaryotic cells and show activity against a large array of intracellular organisms, but systematic studies aimed at examining their pharmacodynamic profile against intracellular bacteria are scarce. The present work aims at comparing intracellular-to-extracellular activities in this context. METHODS: We assessed the activities of ciprofloxacin, levofloxacin, moxifloxacin and garenoxacin against the extracellular (broth) and intracellular (infected J774 macrophages) forms of Listeria monocytogenes (cytosolic infection) and Staphylococcus aureus (phagolysosomal infection) using a range of clinically meaningful extracellular concentrations (0.06-4 mg/L). RESULTS: All four quinolones displayed concentration-dependent bactericidal activity against extracellular and intracellular L. monocytogenes and S. aureus for extracellular concentrations in the range 1-4-fold their MIC. Compared at equipotent extracellular concentrations, intracellular activities against L. monocytogenes were roughly equal to those that were extracellular, but were 50-100 times lower against S. aureus. Because quinolones accumulate in cells (ciprofloxacin, approximately 3 times; levofloxacin, approximately 5 times; garenoxacin, approximately 10 times, moxifloxacin, approximately 13 times), these data show that, intracellularly, quinolones are 5-10 times less potent against L. monocytogenes (P=0.065 [ANCOVA]), and at least 100 times less potent (P < 0.0001) against S. aureus. Because of their lower MICs and higher accumulation levels, garenoxacin and moxifloxacin were, however, more active than ciprofloxacin and levofloxacin when compared at similar extracellular concentrations. CONCLUSIONS: Quinolone activity is reduced intracellulary. This suggests that either only a fraction of cell-associated quinolones exert an antibacterial effect, or that intracellular activity is defeated by the local environment, or that intracellular bacteria only poorly respond to the action of quinolones.
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