This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Carryn, S.
Right arrow Articles by Tulkens, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Carryn, S.
Right arrow Articles by Tulkens, P. M.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, July 2002, p. 2095-2103, Vol. 46, No. 7
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.7.2095-2103.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Comparative Intracellular (THP-1 Macrophage) and Extracellular Activities of ß-Lactams, Azithromycin, Gentamicin, and Fluoroquinolones against Listeria monocytogenes at Clinically Relevant Concentrations

Stéphane Carryn,* Françoise Van Bambeke, Marie-Paule Mingeot-Leclercq, and Paul M. Tulkens

Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, Brussels, Belgium

Received 10 September 2001/ Returned for modification 30 January 2002/ Accepted 2 April 2002

The activities of ampicillin, meropenem, azithromycin, gentamicin, ciprofloxacin, and moxifloxacin against intracellular hemolysin-positive Listeria monocytogenes were measured in human THP-1 macrophages and were compared with the extracellular activities observed in broth. All extracellular concentrations were adjusted to explore ranges that are clinically achievable in human serum upon conventional therapy. In broth, ampicillin, meropenem, and azithromycin were only bacteriostatic, whereas gentamicin, ciprofloxacin, and moxifloxacin were strongly bactericidal in a concentration-dependent manner. In cells, ampicillin, meropenem, azithromycin, and ciprofloxacin were slightly bactericidal (0.3- to 0.8-log CFU reductions), moxifloxacin was strongly bactericidal (2.1-log CFU reduction), and gentamicin was virtually inactive. The difference in the efficacies of moxifloxacin and ciprofloxacin in cells did not result from a difference in levels of accumulation in cells (6.96 ± 1.05 versus 7.75 ± 1.03) and was only partially explainable by the difference in the MICs (0.58 ± 0.04 versus 1.40 ± 0.17 mg/liter). Further analysis showed that intracellular moxifloxacin expressed only approximately 1/7 of the activity demonstrated against extracellular bacteria and ciprofloxacin expressed only 1/15 of the activity demonstrated against extracellular bacteria. Gentamicin did not increase the intracellular activities of the other antibiotics tested. The data suggest (i) that moxifloxacin could be of potential interest for eradication of the intracellular forms of L. monocytogenes, (ii) that the cellular accumulation of an antibiotic is not the only determinant of its intracellular activity (for fluoroquinolones, it is actually a self-defeating process as far as activity is concerned), and (iii) that pharmacodynamics (activity-to-concentration relationships) need to be considered for the establishment of efficacy against intracellular bacteria, just as they are for the establishment of efficacy against extracellular infections.

* Corresponding author. Mailing address: Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, UCL 73.70 Avenue E. Mounier 73, B-1200 Brussels, Belgium. Phone: 32-2-7647375. Fax: 32-2-7647373. E-mail: stephane.carryn{at}facm.ucl.ac.be.

Antimicrobial Agents and Chemotherapy, July 2002, p. 2095-2103, Vol. 46, No. 7
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.7.2095-2103.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lemaire, S., Van Bambeke, F., Appelbaum, P. C., Tulkens, P. M. (2009). Cellular pharmacokinetics and intracellular activity of torezolid (TR-700): studies with human macrophage (THP-1) and endothelial (HUVEC) cell lines. J Antimicrob Chemother 64: 1035-1043 [Abstract] [Full Text]  
  • Lemaire, S., Van Bambeke, F., Tulkens, P. M. (2009). Cellular Accumulation and Pharmacodynamic Evaluation of the Intracellular Activity of CEM-101, a Novel Fluoroketolide, against Staphylococcus aureus, Listeria monocytogenes, and Legionella pneumophila in Human THP-1 Macrophages. Antimicrob. Agents Chemother. 53: 3734-3743 [Abstract] [Full Text]  
  • Sandberg, A., Hessler, J. H. R., Skov, R. L., Blom, J., Frimodt-Moller, N. (2009). Intracellular Activity of Antibiotics against Staphylococcus aureus in a Mouse Peritonitis Model. Antimicrob. Agents Chemother. 53: 1874-1883 [Abstract] [Full Text]  
  • Lismond, A., Tulkens, P. M., Mingeot-Leclercq, M.-P., Courvalin, P., Van Bambeke, F. (2008). Cooperation between Prokaryotic (Lde) and Eukaryotic (MRP) Efflux Transporters in J774 Macrophages Infected with Listeria monocytogenes: Studies with Ciprofloxacin and Moxifloxacin. Antimicrob. Agents Chemother. 52: 3040-3046 [Abstract] [Full Text]  
  • Grayo, S., Lott-Desroches, M.-C., Dussurget, O., Respaud, R., Fontanet, A., Join-Lambert, O., Singlas, E., Le Monnier, A. (2008). Rapid Eradication of Listeria monocytogenes by Moxifloxacin in a Murine Model of Central Nervous System Listeriosis. Antimicrob. Agents Chemother. 52: 3210-3215 [Abstract] [Full Text]  
  • Lemaire, S., Olivier, A., Van Bambeke, F., Tulkens, P. M., Appelbaum, P. C., Glupczynski, Y. (2008). Restoration of Susceptibility of Intracellular Methicillin-Resistant Staphylococcus aureus to {beta}-Lactams: Comparison of Strains, Cells, and Antibiotics. Antimicrob. Agents Chemother. 52: 2797-2805 [Abstract] [Full Text]  
  • Grayo, S., Join-Lambert, O., Desroches, M. C., Le Monnier, A. (2008). Comparison of the In Vitro Efficacies of Moxifloxacin and Amoxicillin against Listeria monocytogenes. Antimicrob. Agents Chemother. 52: 1697-1702 [Abstract] [Full Text]  
  • Shandil, R. K., Jayaram, R., Kaur, P., Gaonkar, S., Suresh, B. L., Mahesh, B. N., Jayashree, R., Nandi, V., Bharath, S., Balasubramanian, V. (2007). Moxifloxacin, Ofloxacin, Sparfloxacin, and Ciprofloxacin against Mycobacterium tuberculosis: Evaluation of In Vitro and Pharmacodynamic Indices That Best Predict In Vivo Efficacy. Antimicrob. Agents Chemother. 51: 576-582 [Abstract] [Full Text]  
  • Barcia-Macay, M., Seral, C., Mingeot-Leclercq, M.-P., Tulkens, P. M., Van Bambeke, F. (2006). Pharmacodynamic Evaluation of the Intracellular Activities of Antibiotics against Staphylococcus aureus in a Model of THP-1 Macrophages. Antimicrob. Agents Chemother. 50: 841-851 [Abstract] [Full Text]  
  • Ong, C. T., Babalola, C. P., Nightingale, C. H., Nicolau, D. P. (2005). Penetration, efflux and intracellular activity of tigecycline in human polymorphonuclear neutrophils (PMNs). J Antimicrob Chemother 56: 498-501 [Abstract] [Full Text]  
  • Michot, J.-M., Seral, C., Van Bambeke, F., Mingeot-Leclercq, M.-P., Tulkens, P. M. (2005). Influence of Efflux Transporters on the Accumulation and Efflux of Four Quinolones (Ciprofloxacin, Levofloxacin, Garenoxacin, and Moxifloxacin) in J774 Macrophages. Antimicrob. Agents Chemother. 49: 2429-2437 [Abstract] [Full Text]  
  • Lemaire, S., Van Bambeke, F., Mingeot-Leclercq, M.-P., Tulkens, P. M. (2005). Activity of three {beta}-lactams (ertapenem, meropenem and ampicillin) against intraphagocytic Listeria monocytogenes and Staphylococcus aureus. J Antimicrob Chemother 55: 897-904 [Abstract] [Full Text]  
  • Seral, C., Barcia-Macay, M., Mingeot-Leclercq, M. P., Tulkens, P. M., Van Bambeke, F. (2005). Comparative activity of quinolones (ciprofloxacin, levofloxacin, moxifloxacin and garenoxacin) against extracellular and intracellular infection by Listeria monocytogenes and Staphylococcus aureus in J774 macrophages. J Antimicrob Chemother 55: 511-517 [Abstract] [Full Text]  
  • Janda, J., Schoneberger, P., Skoberne, M., Messerle, M., Russmann, H., Geginat, G. (2004). Cross-Presentation of Listeria-Derived CD8 T Cell Epitopes Requires Unstable Bacterial Translation Products. J. Immunol. 173: 5644-5651 [Abstract] [Full Text]  
  • Michot, J.-M., Van Bambeke, F., Mingeot-Leclercq, M.-P., Tulkens, P. M. (2004). Active Efflux of Ciprofloxacin from J774 Macrophages through an MRP-Like Transporter. Antimicrob. Agents Chemother. 48: 2673-2682 [Abstract] [Full Text]  
  • Ben Abdelaziz, H., Lemaire, S., Carryn, S., Van Bambeke, F., Mingeot-Leclercq, M.-P., Tulkens, P. M. (2004). Inhibition of TNF-{alpha} production in THP-1 macrophages by glatiramer acetate does not alter their susceptibility to infection by Listeria monocytogenes and does not impair the efficacy of ampicillin or moxifloxacin against intracellular bacteria. J Antimicrob Chemother 54: 288-289 [Full Text]  
  • Chanteux, H., Mingeot-Leclercq, M.-P., Sonveaux, E., Van Bambeke, F., Tulkens, P. M. (2003). Intracellular accumulation and activity of ampicillin used as free drug and as its phthalimidomethyl or pivaloyloxymethyl ester (pivampicillin) against Listeria monocytogenes in J774 macrophages. J Antimicrob Chemother 52: 610-615 [Abstract] [Full Text]  
  • Jayaram, R., Gaonkar, S., Kaur, P., Suresh, B. L., Mahesh, B. N., Jayashree, R., Nandi, V., Bharat, S., Shandil, R. K., Kantharaj, E., Balasubramanian, V. (2003). Pharmacokinetics-Pharmacodynamics of Rifampin in an Aerosol Infection Model of Tuberculosis. Antimicrob. Agents Chemother. 47: 2118-2124 [Abstract] [Full Text]  
  • Seral, C., Van Bambeke, F., Tulkens, P. M. (2003). Quantitative Analysis of Gentamicin, Azithromycin, Telithromycin, Ciprofloxacin, Moxifloxacin, and Oritavancin (LY333328) Activities against Intracellular Staphylococcus aureus in Mouse J774 Macrophages. Antimicrob. Agents Chemother. 47: 2283-2292 [Abstract] [Full Text]  
  • Seral, C., Carryn, S., Tulkens, P. M., Van Bambeke, F. (2003). Influence of P-glycoprotein and MRP efflux pump inhibitors on the intracellular activity of azithromycin and ciprofloxacin in macrophages infected by Listeria monocytogenes or Staphylococcus aureus. J Antimicrob Chemother 51: 1167-1173 [Abstract] [Full Text]  
  • Carryn, S., Van Bambeke, F., Mingeot-Leclercq, M.-P., Tulkens, P. M. (2003). Activity of {beta}-lactams (ampicillin, meropenem), gentamicin, azithromycin and moxifloxacin against intracellular Listeria monocytogenes in a 24 h THP-1 human macrophage model. J Antimicrob Chemother 51: 1051-1052 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»