1: J Antimicrob Chemother. 2008 Sep;62(3):518-21. Epub 2008 Jun 10. Contrasting effects of human THP-1 cell differentiation on levofloxacin and moxifloxacin intracellular accumulation and activity against Staphylococcus aureus and Listeria monocytogenes. Van de Velde S, Nguyen HA, Van Bambeke F, Tulkens PM, Grellet J, Dubois V, Quentin C, Saux MC. Unité de pharmacologie cellulaire et moléculaire, Université catholique de Louvain, Bruxelles, Belgium. BACKGROUND AND AIMS: Listeria monocytogenes and Staphylococcus aureus invade and multiply in THP-1 monocytes. Fluoroquinolones accumulate in these cells, but are less active against intracellular than extracellular forms of L. monocytogenes and S. aureus. We examined whether differentiation of THP-1 monocytes into adherent, macrophage-like cells increases fluoroquinolone uptake and activity. METHODS: THP-1 monocytes were differentiated with phorbol myristate acetate (PMA) and compared with unstimulated cells for: (i) moxifloxacin and levofloxacin accumulation; and (ii) activity against phagocytosed L. monocytogenes and S. aureus (5 h contact). RESULTS: The differentiation of THP-1 monocytes caused: (i) a 3- to 4-fold increase in moxifloxacin uptake and a significant increase in its activity against intracellular L. monocytogenes (from 1.3 log(10) to 2.1 log(10) cfu decrease compared with the post-phagocytosis inoculum), but not against S. aureus (1.0-1.2 log(10) cfu decrease throughout); and (ii) no change in levofloxacin accumulation and intracellular activity against either L. monocytogenes or S. aureus. CONCLUSIONS: Although differentiation of monocytes enhances the uptake and activity of moxifloxacin against L. monocytogenes, this cannot be extended to other intracellular bacteria and to levofloxacin. These results further demonstrate that antibiotic intracellular accumulation and activity are not necessarily linked and suggest that intracellular drug and pathogen combinations must be studied individually. PMID: 18544595 [PubMed - in process] Related Links Comparative activity of quinolones (ciprofloxacin, levofloxacin, moxifloxacin and garenoxacin) against extracellular and intracellular infection by Listeria monocytogenes and Staphylococcus aureus in J774 macrophages. [J Antimicrob Chemother. 2005] PMID:15731197 Factors compromising the activity of moxifloxacin against intracellular Staphylococcus aureus. [J Antimicrob Chemother. 2007] PMID:17353222 Comparative intracellular (THP-1 macrophage) and extracellular activities of beta-lactams, azithromycin, gentamicin, and fluoroquinolones against Listeria monocytogenes at clinically relevant concentrations. [Antimicrob Agents Chemother. 2002] PMID:12069960 Effect of recombinant human gamma interferon on intracellular activities of antibiotics against Listeria monocytogenes in the human macrophage cell line THP-1. [Antimicrob Agents Chemother. 1996] PMID:8723471 Discrepancy between uptake and intracellular activity of moxifloxacin in a Staphylococcus aureus-human THP-1 monocytic cell model. [Antimicrob Agents Chemother. 2002] PMID:11796332