Table 2. Synergistic activity between the ion channel blockers and isoniazid,rifampicin,amikacin or ofloxacin,against the nine M. tuberculosisstrains.
| Strains | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Drug combinations | H37Rv—Suscep | H37RvΔkatG—INHR | 82/09—MDR | 149/09—XDR | 286/09—XDR | 69/11—MDR | 29/12—XDR | 269/03—INHR | 294/09—INHR | ||||||||||
| Antibiotics | ICB | MIC (μg/ml) | MF | MIC (μg/ml) | MF | MIC (μg/ml) | MF | MIC (μg/ml) | MF | MIC (μg/ml) | MF | MIC (μg/ml) | MF | MIC (μg/ml) | MF | MIC (μg/ml) | MF | MIC (μg/ml) | MF |
| INH | No ICB | 0.1 | - | 128 | - | 3 | - | 3 | - | 20 | - | 20 | - | 3 | - | 10 | - | 0.4 | - |
| + VP | 0.1 | 1 | 128 | 1 | 1 | 3 | 1 | 3 | 1 | 20 | 10 | 2 | 1 | 3 | 10 | 1 | 0.4 | 1 | |
| + TZ | 0.1 | 1 | 128 | 1 | 1 | 3 | 1 | 3 | 20 | 1 | 3 | 7 | 3 | 1 | 3 | 3 | 0.4 | 1 | |
| + CPZ | 0.1 | 1 | 128 | 1 | 1 | 3 | 1 | 3 | 1 | 20 | 3 | 7 | 1 | 3 | 3 | 3 | 0.4 | 1 | |
| + FPX | 0.1 | 1 | 128 | 1 | 1 | 3 | 1 | 3 | 1 | 20 | 3 | 7 | 1 | 3 | 3 | 3 | 0.4 | 1 | |
| + HAL | 0.1 | 1 | 128 | 1 | 1 | 3 | 1 | 3 | 1 | 20 | 10 | 2 | 1 | 3 | 10 | 1 | 0.4 | 1 | |
| RIF | No ICB | 1 | - | - | - | 320 | - | 320 | - | 80 | - | 320 | - | 320 | - | - | - | - | - |
| + VP | 1 | 1 | - | - | 20 | 16 | 20 | 16 | 20 | 4 | 20 | 16 | 20 | 16 | - | - | - | - | |
| + TZ | 1 | 1 | - | - | 320 | 1 | 320 | 1 | 20 | 4 | 320 | 1 | 320 | 1 | - | - | - | - | |
| + CPZ | 1 | 1 | - | - | 320 | 1 | 20 | 16 | 4 | 20 | 20 | 16 | 20 | 16 | - | - | - | - | |
| + FPX | 1 | 1 | - | - | 320 | 1 | 320 | 1 | 4 | 20 | 320 | 1 | 320 | 1 | - | - | - | - | |
| + HAL | 1 | 1 | - | - | 320 | 1 | 320 | 1 | 20 | 4 | 320 | 1 | 320 | 1 | - | - | - | - | |
| AMK | No ICB | 1 | - | - | - | - | - | 640 | - | 4 | - | 40 | - | 640 | - | - | - | - | - |
| + VP | 1 | 1 | - | - | - | - | 640 | 1 | 4 | 1 | 1 | 40 | 640 | 1 | - | - | - | - | |
| + TZ | 1 | 1 | - | - | - | - | 640 | 1 | 4 | 1 | 1 | 40 | 640 | 1 | - | - | - | - | |
| + CPZ | 1 | 1 | - | - | - | - | 40 | 16 | 4 | 1 | 1 | 40 | 40 | 16 | - | - | - | - | |
| + FPX | 1 | 1 | - | - | - | - | 640 | 1 | 4 | 1 | 1 | 40 | 640 | 1 | - | - | - | - | |
| + HAL | 1 | 1 | - | - | - | - | 640 | 1 | 4 | 1 | 1 | 40 | 640 | 1 | - | - | - | - | |
| OFX | No ICB | 1 | - | - | - | - | - | 10 | 10 | - | - | 10 | - | - | - | - | |||
| + VP | 1 | 1 | - | - | - | - | 10 | 1 | 10 | 1 | - | - | 10 | 1 | - | - | - | - | |
| + TZ | 1 | 1 | - | - | - | - | 10 | 1 | 10 | 1 | - | - | 10 | 1 | - | - | - | - | |
| + CPZ | 1 | 1 | - | - | - | - | 10 | 1 | 10 | 1 | - | - | 10 | 1 | - | - | - | - | |
| + FPX | 1 | 1 | - | - | - | - | 10 | 1 | 10 | 1 | - | - | 10 | 1 | - | - | - | - | |
| + HAL | 1 | 1 | - | - | - | - | 10 | 1 | 10 | 1 | - | - | 10 | 1 | - | - | - | - | |
Suscep, susceptible; MF, modulation factor; ICB, ion channel blocker; Δ, deletion; INH, isoniazid; RIF, rifampicin; AMK, amikacin, OFX, ofloxacin; VP, verapamil; TZ, thioridazine; CPZ, chlorpromazine; FPX, flupenthixol; HAL, haloperidol. The lowest concentration tested corresponds to the critical concentration for each antibiotic (see Material and Methods section for details). Synergistic interactions are in bold.