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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Discrepancy between uptake and intracellular activity of moxifloxacin in a Staphylococcus aureus-human THP-1 monocytic cell model.

The correlation between uptake of moxifloxacin by THP-1, a continuous line of monocytic cells devoid of intrinsic bactericidal properties, and its activity against Staphylococcus aureus ATCC 25923, a susceptible reference strain (MIC and minimal bactericidal concentration of moxifloxacin, 0.1 mg/liter), was studied in a 5-h assay. The uptake of the drug, added to the culture medium at 0.2 to 32 mg/liter, was evaluated by high-performance liquid chromatography. The ratio of the cellular to extracellular concentration of moxifloxacin reached, at equilibrium, 4.36 +/- 0.39 in uninfected cells and 6.25 +/- 0.41 in infected cells. The intracellular activity of moxifloxacin, introduced into the extracellular fluid at 0.06 to 8 mg/liter, was determined by the enumeration of viable bacteria. At concentrations < or =0.2 mg/liter, the drug inhibited only the intracellular bacterial growth, while at concentrations > or =0.5 mg/liter, it decreased the bacterial inoculum by less than 1 log(10) unit, with a maximum effect at 3 to 4 h, followed by regrowth of surviving bacteria to 80 to 120% of the original level at 5 h. In contrast, when killing curves were determined by using Mueller-Hinton broth with a similar inoculum (10(7) CFU/ml), moxifloxacin at concentrations > or =0.2 mg/liter reduced the inoculum by at least 3 log(10) units at 3 to 4 h, leaving < or =0.1% survival at 24 h. Persisters exhibited a fluoroquinolone susceptibility identical to that of S. aureus ATCC 25923. Our data indicate that moxifloxacin at therapeutic extracellular concentrations accumulates approximately sixfold in infected THP-1 cells and remains active intracellularly, but significantly less active than under in vitro conditions.[1]


  1. Discrepancy between uptake and intracellular activity of moxifloxacin in a Staphylococcus aureus-human THP-1 monocytic cell model. Paillard, D., Grellet, J., Dubois, V., Saux, M.C., Quentin, C. Antimicrob. Agents Chemother. (2002) [Pubmed]
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