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]

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