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Antimicrobial Agents and Chemotherapy, February 2007, p. 645-650, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.00821-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Curing Mycobacterium ulcerans Infection in Mice with a Combination of Rifampin-Streptomycin or Rifampin-Amikacin

Laboratoire de Bactériologie-Hygiène, Faculté de Médecine Pierre et Marie Curie (Université Paris 6), and Centre National de Référence des Mycobactéries et de la Résistance aux Antituberculeux, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Paris, France

Received 6 July 2006/ Returned for modification 10 August 2006/ Accepted 25 October 2006

The curing activities of various durations of treatment with a combination of rifampin (RIF) and either streptomycin (STR) or amikacin (AMK) in murine Mycobacterium ulcerans infection were compared in two experiments. In the first experiment, treatment was begun 1 week after infection, when the inflammatory footpad lesion had not yet occurred (preventive model), and in the second experiment, treatment was begun 6 weeks after infection, when inflammatory footpad lesions were established (curative model). In the first experiment, 4 weeks of treatment with daily RIF-STR or RIF-AMK was able to postpone the occurrence of footpad lesion by 12 weeks (RIF-STR) or 17 weeks (RIF-AMK), thus demonstrating their promising bactericidal activities, but neither treatment was able to prevent the late occurrence of footpad lesions. In the second experiment, the overall cure rates, as assessed by the lack of rebound of inflammatory lesions or remultiplication of M. ulcerans, were only 62% after 2 weeks of treatment with RIF and an aminoglycoside and 85% after 4 weeks; but the cure rate reached 100% after 8 or 12 weeks of treatment. The cure rates were slightly higher with the AMK-containing combination than with the STR-containing combination, but the difference was at the limit of significance (P = 0.07). These results show that in the murine model of Buruli ulcer, 8 weeks is the optimal duration of treatment with a combination of RIF and an aminoglycoside.

Published ahead of print on 13 November 2006.

This article has been cited by other articles:

• Ji, B., Chauffour, A., Robert, J., Jarlier, V. (2008). Bactericidal and Sterilizing Activities of Several Orally Administered Combined Regimens against Mycobacterium ulcerans in Mice. Antimicrob. Agents Chemother. 52: 1912-1916 [Abstract] [Full Text]  
• Ji, B., Chauffour, A., Robert, J., Lefrancois, S., Jarlier, V. (2007). Orally Administered Combined Regimens for Treatment of Mycobacterium ulcerans Infection in Mice. Antimicrob. Agents Chemother. 51: 3737-3739 [Abstract] [Full Text]