Contrasting effects of human THP-1 cell differentiation on levofloxacin and moxifloxacin intracellular accumulation and activity against Staphylococcus aureus and Listeria monocytogenes.
OBJECTIVE
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.
Van de Velde
Sébastien
S
Unité de pharmacologie cellulaire et moléculaire, Université catholique de Louvain, Bruxelles, Belgium.
Nguyen
Hoang Anh
HA
Van Bambeke
Françoise
F
Tulkens
Paul M
PM
Grellet
Jean
J
Dubois
Véronique
V
Quentin
Claudine
C
Saux
Marie-Claude
MC
D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology*; D001372:Aza Compounds / Q000378:metabolism* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015169:Colony Count, Microbial; D003593:Cytoplasm / Q000737:chemistry / Q000382:microbiology; D024841:Fluoroquinolones; D006801:Humans; D064704:Levofloxacin; D008089:Listeria monocytogenes / Q000187:drug effects*; D050296:Microbial Viability; D009000:Monocytes / Q000378:metabolism* / Q000382:microbiology*; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000378:metabolism* / Q000494:pharmacology*; D011804:Quinolines / Q000378:metabolism* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D015242:Ofloxacin; D000077266:Moxifloxacin