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Antimicrobial Agents and Chemotherapy, February 2002, p. 288-293, Vol. 46, No. 2
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.2.288-293.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Discrepancy between Uptake and Intracellular Activity of Moxifloxacin in a Staphylococcus aureus-Human THP-1 Monocytic Cell Model

Delphine Paillard,1,2 Jean Grellet,1 Véronique Dubois,2 Marie-Claude Saux,1 and Claudine Quentin2*

Laboratoire de Pharmacocinétique,,1 Laboratoire de Microbiologie, Faculté de Pharmacie, Université de Bordeaux 2, Bordeaux, France2

Received 14 May 2001/ Returned for modification 13 August 2001/ Accepted 22 October 2001

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.

* Corresponding author. Mailing address: Laboratoire de Microbiologie, UFR des Sciences Pharmaceutiques, Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. Phone: (33) 5.57.57.10.75. Fax: (33) 5.56.90.90.72. E-mail: claudine.quentin{at}bacterio.u-bordeaux2.fr.

Antimicrobial Agents and Chemotherapy, February 2002, p. 288-293, Vol. 46, No. 2
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.2.288-293.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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