Evaluating Synergistic Drug Combinations for Tuberculosis

For drug combination studies, MABA was used utilizing similar methodology as described above. For the two drug combination studies, isoniazid (Sigma-Aldrich, St. Luis, MO, USA) at 0.2 µg/mL, rifampicin (Sigma-Aldrich) at 0.026 ng/mL, cycloserine (Sigma-Aldrich) at 5.5 µg/mL, and clarithromycin (Sigma-Aldrich) at 0.09 µg/mL concentrations were used. For the three-drug combination studies, isoniazid at 0.05 µg/mL and rifampicin at 0.012 ng/mL concentrations, respectively, were used. The combination effect of compounds was determined by calculating the combination index (CI). CI was calculated as the sum of the individual drug effect divided by the combination effect of the drugs. If CI values were <1.0, this indicated a synergistic effect (i.e., the combined effect was greater than the sum of their individual effects). If CI = 1.0, this indicated an additive effect (i.e., the combined effect was equal to the sum of their individual effects) and if CI >1.0, this indicated an antagonistic effect (i.e., the combined effect was less than the sum of their individual effects) [64 (link),65 (link),66 (link)].