Bactericidal and Sterilizing Activities of Several Orally Administered Combined Regimens against Mycobacterium ulcerans in Mice

Treatment with rifampin-clarithromycin or moxifloxacin-clarithromycin for 8 weeks displayed promising bactericidal activity against Mycobacterium ulcerans in mice; none of the mice treated with rifampin-clarithromycin relapsed, whereas 59% of those treated with moxifloxacin-clarithromycin relapsed after treatment was stopped. The bactericidal and sterilizing activities of the five-times-weekly (5/7) administration of 5 mg of rifapentine/kg of body weight, either alone or in combination, were virtually identical to those of the corresponding regimens with 10 mg of rifampin/kg of body weight; however, because of the long half-life of rifapentine, accumulation of the drug after 5/7 administration is a concern. The bactericidal activity of 20 mg/kg rifapentine in monotherapy or 20 mg/kg rifapentine in combination with 150 mg/kg streptomycin or 200 mg/kg moxifloxacin administered twice weekly was as effective as the corresponding regimens containing 10 mg/kg rifampin administered 5/7, suggesting that Buruli ulcer might be treated with intermittently administered rifapentine-containing combinations.