This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 Nguyen, H. A.
Right arrow Articles by Van Bambeke, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nguyen, H. A.
Right arrow Articles by Van Bambeke, F.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2009, p. 1443-1449, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.01146-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Intracellular Activity of Antibiotics in a Model of Human THP-1 Macrophages Infected by a Staphylococcus aureus Small-Colony Variant Strain Isolated from a Cystic Fibrosis Patient: Study of Antibiotic Combinations{triangledown} ,{dagger}

Hoang Anh Nguyen,1 Olivier Denis,2 Anne Vergison,3 Paul M. Tulkens,1 Marc J. Struelens,2 and Françoise Van Bambeke1*

Université Catholique de Louvain, Louvain Drug Research Institute, Unité de Pharmacologie Cellulaire et Moléculaire,1 Hôpital Erasme, Department of Microbiology, Laboratoire de Référence MRSA-Staphylocoques,2 Hôpital des Enfants Reine Fabiola, Département de Maladies Infectieuses Pédiatriques, Université Libre de Bruxelles, Brussels, Belgium3

Received 26 August 2008/ Returned for modification 10 December 2008/ Accepted 17 January 2009

In a companion paper (H. A. Nguyen et al., Antimicrob. Agents Chemother. 53:1434-1442, 2009), we showed that vancomycin, oxacillin, fusidic acid, clindamycin, linezolid, and daptomycin are poorly active against the intracellular form of a thymidine-dependent small-colony variant (SCV) strain isolated from a cystic fibrosis patient and that the activity of quinupristin-dalfopristin, moxifloxacin, rifampin, and oritavancin remains limited (2- to 3-log CFU reduction) compared to their extracellular activity. Antibiotic combination is a well-known strategy to improve antibacterial activity, which was examined here against an intracellular SCV strain using combinations with either rifampin or oritavancin. Time-kill curve analysis using either concentrations that caused a static effect for each antibiotic individually or concentrations corresponding to the maximum concentration in human serum showed largely divergent effects that were favorable when antibiotics were combined with rifampin at low concentrations only and with oritavancin at both low and high concentrations. The nature of the interaction between rifampin, oritavancin, and moxifloxacin was further examined using the fractional maximal effect method, which allows categorization of the effects of combinations when dose-effect relationships are not linear. Rifampin and oritavancin were synergistic at all concentration ratios investigated. Oritavancin and moxifloxacin were also synergistic but at high oritavancin concentrations only. Rifampin and moxifloxacin were additive. This approach may help in better assessing and improving the activity of antibiotics against intracellular SCV strains.

* Corresponding author. Mailing address: Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, UCL73.70 avenue Mounier 73, 1200 Brussels, Belgium. Phone: 32 2 764 73 78. Fax: 32 2 764 73 73. E-mail: francoise.vanbambeke{at}uclouvain.be

{triangledown} Published ahead of print on 2 February 2009.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.

Antimicrobial Agents and Chemotherapy, April 2009, p. 1443-1449, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.01146-08
Copyright © 2009, 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]  
  • Nguyen, H. M., Graber, C. J. (2009). Limitations of antibiotic options for invasive infections caused by methicillin-resistant Staphylococcus aureus: is combination therapy the answer?. J Antimicrob Chemother 0: dkp377v1-dkp377 [Abstract] [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»