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 Ibrahim, M.
Right arrow Articles by Veziris, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ibrahim, M.
Right arrow Articles by Veziris, N.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2007, p. 1011-1015, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00898-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Synergistic Activity of R207910 Combined with Pyrazinamide against Murine Tuberculosis{triangledown}

M. Ibrahim,1 K. Andries,2 N. Lounis,2 A. Chauffour,1 C. Truffot-Pernot,1 V. Jarlier,1 and N. Veziris1*

Laboratoire de Bactériologie, Faculté de Médecine Pitié-Salpêtrière, Université Pierre et Marie Curie Paris 6 and Centre National de Référence de la Résistance des Mycobactéries aux Antituberculeux, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Paris, France,1 Antimicrobial Research, Tibotec Pharmaceuticals, Ltd., Johnson & Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium2

Received 20 July 2006/ Returned for modification 8 September 2006/ Accepted 22 November 2006

In previous studies, the diarylquinoline R207910 (also known as TMC207) was demonstrated to have high bactericidal activity when combined with first- or second-line antituberculous drugs. Here we extend the evaluation of R207910 in the curative model of murine tuberculosis by assessing the activities of one-, two-, and three-drug combinations containing R207910 and isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), or moxifloxacin (MXF) in the setting of a high initial bacillary load (7.2 log10 CFU). Two months of treatment with the combinations R207910-PZA, R207910-PZA-INH, R207910-PZA-RIF, or R207910-PZA-MXF resulted in culture-negative lung homogenates in 70 to 100% of the mice, while mice treated with INH-RIF-PZA (the reference regimen) or RIF-MXF-PZA remained culture positive. Combinations including R207910 but not PZA (e.g., R207910-INH-RIF and R207910-MXF-RIF) were less active than R207910-PZA-containing regimens administered either alone or with the addition of INH, RIF, or MXF. These results reveal a synergistic interaction between R207910 and PZA. Three-drug combinations containing these two drugs and INH, RIF, or MXF have the potential to significantly shorten the treatment duration in patients, provided that these results can be confirmed in long-term experiments including periods of relapse.

* Corresponding author. Mailing address: Laboratoire de Bactériologie, Faculté de Médecine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris Cedex 13, France. Phone: (33) 1 40 77 97 46. Fax: (33) 1 45 82 75 77. E-mail: veziris{at}chups.jussieu.fr.

{triangledown} Published ahead of print on 18 December 2006.

Antimicrobial Agents and Chemotherapy, March 2007, p. 1011-1015, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00898-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ibrahim, M., Truffot-Pernot, C., Andries, K., Jarlier, V., Veziris, N. (2009). Sterilizing Activity of R207910 (TMC207)-containing Regimens in the Murine Model of Tuberculosis. Am. J. Respir. Crit. Care Med. 180: 553-557 [Abstract] [Full Text]  
  • Diacon, A. H., Pym, A., Grobusch, M., Patientia, R., Rustomjee, R., Page-Shipp, L., Pistorius, C., Krause, R., Bogoshi, M., Churchyard, G., Venter, A., Allen, J., Palomino, J. C., De Marez, T., van Heeswijk, R. P.G., Lounis, N., Meyvisch, P., Verbeeck, J., Parys, W., de Beule, K., Andries, K., Neeley, D. F. M. (2009). The Diarylquinoline TMC207 for Multidrug-Resistant Tuberculosis. NEJM 360: 2397-2405 [Abstract] [Full Text]  
  • van den Boogaard, J., Kibiki, G. S., Kisanga, E. R., Boeree, M. J., Aarnoutse, R. E. (2009). New Drugs against Tuberculosis: Problems, Progress, and Evaluation of Agents in Clinical Development. Antimicrob. Agents Chemother. 53: 849-862 [Full Text]  
  • Veziris, N., Ibrahim, M., Lounis, N., Chauffour, A., Truffot-Pernot, C., Andries, K., Jarlier, V. (2009). A Once-Weekly R207910-containing Regimen Exceeds Activity of the Standard Daily Regimen in Murine Tuberculosis. Am. J. Respir. Crit. Care Med. 179: 75-79 [Abstract] [Full Text]  
  • Hong, S., Pedersen, P. L. (2008). ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas. Microbiol. Mol. Biol. Rev. 72: 590-641 [Abstract] [Full Text]  
  • Guy, E. S., Mallampalli, A. (2008). Review: Managing TB in the 21st century: existing and novel drug therapies. Ther Adv Respir Dis 2: 401-408 [Abstract]  
  • Lounis, N., Gevers, T., Van Den Berg, J., Andries, K. (2008). Impact of the Interaction of R207910 with Rifampin on the Treatment of Tuberculosis Studied in the Mouse Model. Antimicrob. Agents Chemother. 52: 3568-3572 [Abstract] [Full Text]  
  • Rao, S. P. S., Alonso, S., Rand, L., Dick, T., Pethe, K. (2008). The protonmotive force is required for maintaining ATP homeostasis and viability of hypoxic, nonreplicating Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 105: 11945-11950 [Abstract] [Full Text]  
  • Rustomjee, R., Diacon, A. H., Allen, J., Venter, A., Reddy, C., Patientia, R. F., Mthiyane, T. C. P., De Marez, T., van Heeswijk, R., Kerstens, R., Koul, A., De Beule, K., Donald, P. R., McNeeley, D. F. (2008). Early Bactericidal Activity and Pharmacokinetics of the Diarylquinoline TMC207 in Treatment of Pulmonary Tuberculosis. Antimicrob. Agents Chemother. 52: 2831-2835 [Abstract] [Full Text]  
  • Lenaerts, A. J., Hoff, D., Aly, S., Ehlers, S., Andries, K., Cantarero, L., Orme, I. M., Basaraba, R. J. (2007). Location of Persisting Mycobacteria in a Guinea Pig Model of Tuberculosis Revealed by R207910. Antimicrob. Agents Chemother. 51: 3338-3345 [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»