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JAC Advance Access published online on June 10, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn232
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Contrasting effects of human THP-1 cell differentiation on levofloxacin and moxifloxacin intracellular accumulation and activity against Staphylococcus aureus and Listeria monocytogenes

Sébastien Van de Velde1,{dagger}, Hoang Anh Nguyen1,2,{dagger}, Françoise Van Bambeke1,*, Paul M. Tulkens1, Jean Grellet2, Véronique Dubois2, Claudine Quentin2 and Marie-Claude Saux2

1 Unité de pharmacologie cellulaire et moléculaire, Université catholique de Louvain, Bruxelles, Belgium 2 Laboratoire de Pharmacocinétique et de Pharmacie Clinique et Laboratoire de Microbiologie, Université Victor Ségalen Bordeaux 2, Bordeaux, France

Received 27 February 2008; returned 16 April 2008; revised 17 May 2008; accepted 19 May 2008

* Correspondence address. UCL 7370 Avenue E. Mounier 73, B-1200 Bruxelles, Belgium. Tel: +32-2-764-7378; Fax: +32-2-764-7373; E-mail: vanbambeke{at}facm.ucl.ac.be

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 log10 to 2.1 log10 cfu decrease compared with the post-phagocytosis inoculum), but not against S. aureus (1.0–1.2 log10 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.

Key Words: phorbol myristate acetate , macrophages , phagocytosis , cytosol , phagolysosomes

{dagger} These authors contributed equally to this work.


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