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Antimicrobial Agents and Chemotherapy, October 2005, p. 4015-4019, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4015-4019.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Efficient Intermittent Rifapentine-Moxifloxacin-Containing Short-Course Regimen for Treatment of Tuberculosis in Mice

N. Veziris,* N. Lounis,{dagger} A. Chauffour, C. Truffot-Pernot, and V. Jarlier

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, Paris, France

Received 13 May 2005/ Returned for modification 14 June 2005/ Accepted 25 July 2005

Long-half-life drugs raise the hope of once-a-week administration of antituberculous treatment. In a previous study with the murine model of tuberculosis, the most active intermittent regimen which contained rifapentine (RFP), isoniazid (INH), and moxifloxacin (MXF) given once a week during 5.5 months, preceded by 2 weeks of daily treatment with INH, rifampin (RIF), pyrazinamide (PZA), and MXF, was less active than the standard 6-month daily RIF-INH-PZA regimen. We evaluated with the same model similar regimens in which we increased the dosing of rifapentine from 10 to 15 mg/kg of body weight and of moxifloxacin from 100 to 400 mg/kg. Mice infected intravenously by 6.2 x106 CFU of Mycobacterium tuberculosis H37Rv were treated 2 weeks later when infection was established. After 6 months of treatment, all mice had negative lung culture. After 3 months of follow-up, no relapse occurred in the two groups that received moxifloxacin at 400 mg/kg, whatever the dosage of RFP, and in the group receiving the standard RIF-INH-PZA control regimen. In contrast, in the two groups receiving moxifloxacin at a lower dosage, the relapse rate was significantly higher (13% in mice receiving RFP at 15 mg/kg and 27% in those receiving RFP at 10 mg/kg). Finally, the fully intermittent once-a-week regimen (26 drug ingestions) of INH, RFP (15 mg/kg), and MXF (400 mg/kg) led to a relapse rate of 11%. In conclusion, when used at high dosage, rifapentine and moxifloxacin are very efficient when combined with isoniazid in a once-a-week treatment in mouse tuberculosis.

* 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.

{dagger} Present address: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21231.

Antimicrobial Agents and Chemotherapy, October 2005, p. 4015-4019, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4015-4019.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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  • 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]  


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