Discrepancy between Uptake and Intracellular Activity of Moxifloxacin in a Staphylococcus aureus-Human THP-1 Monocytic Cell Model
AUTOR(ES)
Paillard, Delphine
FONTE
American Society for Microbiology
RESUMO
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 ≤0.2 mg/liter, the drug inhibited only the intracellular bacterial growth, while at concentrations ≥0.5 mg/liter, it decreased the bacterial inoculum by less than 1 log10 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 (107 CFU/ml), moxifloxacin at concentrations ≥0.2 mg/liter reduced the inoculum by at least 3 log10 units at 3 to 4 h, leaving ≤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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=127041Documentos Relacionados
- Plectasin Shows Intracellular Activity against Staphylococcus aureus in Human THP-1 Monocytes and in a Mouse Peritonitis Model▿
- Induction of Proinflammatory Responses in the Human Monocytic Cell Line THP-1 by Campylobacter jejuni
- Regulation of Proinflammatory Cytokine Expression by Shiga Toxin 1 and/or Lipopolysaccharides in the Human Monocytic Cell Line THP-1
- Mycoplasma arthritidis-derived superantigen induces proinflammatory monokine gene expression in the THP-1 human monocytic cell line.
- Interleukin-10 Modulates Proinflammatory Cytokines in the Human Monocytic Cell Line THP-1 Stimulated with Borrelia burgdorferi Lipoproteins