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Antimicrobial Agents and Chemotherapy, November 2006, p. 3543-3547, Vol. 50, No. 11
0066-4804/06/$08.00+0     doi:10.1128/AAC.00766-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Combinations of R207910 with Drugs Used To Treat Multidrug-Resistant Tuberculosis Have the Potential To Shorten Treatment Duration{triangledown}

Nacer Lounis,1,2 Nicolas Veziris,1 Aurélie Chauffour,1 Chantal Truffot-Pernot,1 Koen Andries,2* and Vincent Jarlier1

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

Received 23 June 2006/ Returned for modification 28 July 2006/ Accepted 29 August 2006

The objective of the present study was to identify the optimal R207910-containing regimen to administer to patients who cannot receive rifampin (RIF) and isoniazid (INH) because of multidrug-resistant tuberculosis (MDR-TB), concomitant use of antiretroviral drugs, or toxicity. Mice were infected intravenously with 5 x 106 CFU of the H37Rv strain and treated five times per week with R207910 alone or various combinations of R207910 with the second-line drugs amikacin (AMK), pyrazinamide (PZA), moxifloxacin (MXF), and ethionamide (ETH). All R207910-containing regimens were significantly more active than the non-R207910-containing regimens after 1 month of therapy. When given for 2 months, R207910 alone was more active than the WHO standard first-line regimen RIF-INH-PZA. When R207910 was combined with second-line drugs, the combinations were more active than the currently recommended regimen of MDR-TB AMK-ETH-MXF-PZA, and culture negativity of both the lungs and spleen was reached after 2 months of treatment in almost every case.

* Corresponding author. Mailing address: Tibotec Pharmaceuticals Ltd., Johnson & Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium. Phone: 32 14 60 20 33. Fax: 32 14 60 54 03. E-mail: kandries{at}prdbe.jnj.com.

{triangledown} Published ahead of print on 5 September 2006.

Antimicrobial Agents and Chemotherapy, November 2006, p. 3543-3547, Vol. 50, No. 11
0066-4804/06/$08.00+0     doi:10.1128/AAC.00766-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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