It has been determined that co-administration of a rifamycin and a switch-region inhibitor 1) results in synergistic antibacterial effects, enabling efficacy at low, subtoxic doses, and/or 2) results in a low spontaneous resistance frequency, enabling treatment of high-titer infections without treatment failure due to spontaneous resistance. Accordingly, certain embodiments provide composition comprising a rifamycin and a switch region inhibitor, as well as methods of use thereof.
