Response to antibiotic treatment in footpads of mice infected with <i>M</i>. <i>ulcerans</i>.

<p><b>(A) Footpad swelling</b>. After infection of both hind footpads, treatment began when swelling approached grade 2 at week 7. Swelling continued to increase for the next two weeks in untreated control mice (black squares) and in mice treated with clofazimine (CFZ) alone, but was arrested in mice treated with either rifampin and streptomycin (RIF+STR, green circles), rifampin and clarithromycin (RIF+CLR, blue triangles) or rifampin and CFZ (RIF+CFZ, solid red circles) and then declined at a comparable rate to a grade of less than 1 over the 8-week treatment period. <b>(B). Mycolactone A/B concentrations</b>. At day 0, there was 10 ng mycolactone A/B per footpad detected. Mycolactone concentrations continued to increase for the next two weeks in untreated control mice (black squares), reaching 20 ng. Mycolactone production was arrested in mice treated with either RIF+STR (green circles), RIF+CLR (blue triangles), RIF+CFZ (solid red circles), or CFZ alone (orange X) and became undetectable after 6 weeks of RIF+STR or RIF+CFZ. The decline was slower in RIF+CLR mice. <b>(C) <i>M</i>. <i>ulcerans</i> CFU</b>. At day 0, there were 4.64±0.14 <i>M</i>. <i>ulcerans</i> CFU detected in the footpads. CFU numbers increased in untreated controls to 5.37±0.07 by day 10. The CFU levels remained essentially unchanged in mice receiving CFZ alone (4.72±0.59) while in the combination regimens, there was a consistent decline and all mice were culture negative by week 6.