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

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.

Published ahead of print on 5 September 2006.

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