Table 1. Quadruple synergistic combinations among rifampicin, clarithromycin, amoxicillin and clavulanate against M. ulcerans clinical isolates.
MIC (μg/mL) alone | MICsyn (μg/mL) at the MOCC | Fold-Reduction at the MOCC | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Clinical isolate | Geographical origin | RIF | AMX | CLA | RIF | AMX | CLA | RIF | AMX | CLA | Quad FICI |
ITM 063846 | Benin | 0.025 | >32 | 0.125 | 0.0031 | 1 | 0.003 | 8 | 64 | 40 | 0.20 |
ITM 070290 | China | 0.5 | >32 | 1 | 0.0016 | 0.063 | 0.05 | 313 | 1024 | 20 | 0.09 |
ITM 83720 | Mexico | 0.1 | 16 | 0.125 | 0.0063 | 0.063 | 0.003 | 16 | 256 | 40 | 0.13 |
ITM 941327 | Australia | 0.002 | >32 | 0.5 | 0.0004 | 0.031 | 0.025 | 5 | 2065 | 20 | 0.29 |
ITM C05142 | Australia | 0.1 | 16 | 0.125 | 0.0016 | 0.063 | 0.0031 | 64 | 256 | 40 | 0.08 |
ITM C05143 | Mexico | 0.05 | 16 | 0.25 | 0.0008 | 4 | 0.0031 | 64 | 4 | 80 | 0.32 |
ITM C05150 | DR Congo | 0.02 | >32 | 0.25 | 0.0013 | 0.063 | 0.0031 | 16 | 1024 | 80 | 0.12 |
ITM C08756 | Japan | 0.2 | >32 | 0.25 | 0.0016 | 0.250 | 0.0125 | 128 | 256 | 20 | 0.10 |
ITM M000932 | Australia | 0.05 | >32 | 0.063 | 0.0001 | 0.125 | 0.0031 | 640 | 256 | 20 | 0.09 |
Clavulanate was added to the quadruple combination at a fixed dose of 5 μg/mL. For FICI calculations, its MIC was considered as 128 μg/mL. RIF, rifampicin; AMX, amoxicillin; CLA, clarithromycin; MOCC, Most Optimal Combinatorial Concentration; Fold-Reduction, MIC/MICsyn; FICI ≤0.5 indicates synergy.