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Antimicrobial Agents and Chemotherapy, July 2009, p. 2955-2959, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.00011-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Impacts of Dosing Frequency of the Combination Rifampin-Streptomycin on Its Bactericidal and Sterilizing Activities against Mycobacterium ulcerans in Mice{triangledown}

Baohong Ji,* Aurélie Chauffour, Alexandra Aubry, Jérome Robert, Murad Ibrahim, and Vincent Jarlier

Bactériologie-Hygiène, UPMC Université Paris 06, EA 1541, F-75005, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, F-75651 Paris, France

Received 5 January 2009/ Returned for modification 21 January 2009/ Accepted 6 April 2009

Because of operational limitations, a significant proportion of the health centers at the peripheral level are able to provide treatment to Buruli ulcer patients with the combination rifampin (rifampicin)-streptomycin (RIF-STR) only five times weekly (5/7) instead of seven times weekly (7/7), as recommended. The objective of this experiment is to assess the impacts of various dosing frequencies of the combination on its bactericidal and sterilizing activities against Mycobacterium ulcerans in mice. The results demonstrate that the bactericidal activities did not differ significantly among five dosing frequencies of the combination, ranging from seven times to twice weekly, whereas the sterilizing activities differed widely. RIF-STR 7/7 was the only regimen that was able to sterilize the infection after 4 to 8 weeks of treatment; the sterilizing activities associated with reduced dosing frequencies were significantly diminished, and 8 weeks of 5/7 administration yielded a relapse rate greater than the generally accepted level of 5%. We recommend that the duration of treatment with 5/7 administration be prolonged beyond 8 weeks and that additional experiments with mice be carried out, with sufficient statistical power to compare the relapse rates of M. ulcerans infection between 8 weeks of 7/7 administration and 10 and 12 weeks of 5/7 administration of RIF-STR.


* Corresponding author. Mailing address: Bactériologie-Hygiène, Faculté de Médicine Pierre et Marie Curie, Université Paris 6, 91 boulevard de l'Hôpital, 75634 Paris Cedex 13, France. Phone: (331) 40 77 98 67. Fax: (331) 45 82 75 77. E-mail: baohong.ji{at}yahoo.fr

{triangledown} Published ahead of print on 13 April 2009.


Antimicrobial Agents and Chemotherapy, July 2009, p. 2955-2959, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.00011-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.