Clinical efficacy of combination of rifampin and streptomycin for treatment of Mycobacterium ulcerans disease

Abstract

We have evaluated the clinical efficacy of the combination of oral rifampin at 10 mg/kg of body weight and intramuscular streptomycin at 15 mg/kg for 8 weeks (RS8), as recommended by the WHO, in 160 PCR-confirmed cases of Mycobacterium ulcerans disease. In 152 patients (95%) with all forms of disease from early nodules to large ulcers, with or without edema, the lesions healed without recourse to surgery. Eight patients whose ulcers were healing poorly had skin grafting after completion of antibiotics. There were no recurrences among 158 patients reviewed at the 1-year follow-up. The times to complete healing ranged from 2 to 48 weeks, according to the type and size of the lesion, but the average rate of healing (rate of reduction in ulcer diameter) varied widely. Thirteen subjects had positive cultures for M. ulcerans during or after treatment, but all the lesions healed without further antibiotic treatment. Adverse events were rare. These results confirm the efficacy of RS8 delivered in a community setting.

FIG. 1.

Changes in the mean diameter of Buruli ulcer lesions in subjects whose lesions could be traced onto acetate sheets during and after treatment with rifampin and streptomycin for 8 weeks. The lines connect the data for individual subjects. Category I is lesions <5 cm in diameter, category II is lesions 5 to 15 cm, and category III is lesions >15 cm.

FIG. 2.

Time to complete healing. Each dot represents one study subject treated with rifampin and streptomycin for 8 weeks. Horizontal lines represent the medians. The results for eight patients who had surgery, seven patients who defaulted from follow-up after completion of antibiotic treatment, and one patient who died are not included. **, P < 0.005; *, P < 0.01.

FIG. 3.

Rate of healing. The rate of healing was calculated by dividing the diameter of the lesions (in mm) before treatment by the time (in weeks) to complete healing. Horizontal lines represent the median rates of healing, and the broken line shows the overall median healing rate in 72 patients whose lesions were measurable before treatment. The circle highlights edematous lesions with ulceration. MU, M. ulcerans.

FIG. 4.

Semiquantitative culture for M. ulcerans. Samples were cultured from 120 lesions before treatment with RS for 8 weeks and from 64 selected cases responding poorly at 4, 6, 8, or 12 weeks. Negative cultures at each time point are shown as a single point on the baseline. Each line joins the data for samples taken from the same patient, and dotted lines highlight the results for six patients who had positive cultures at two different time points.