Antibacterial activity of DL 473, a new semisynthetic rifamycin derivative

DL 473, a new semisynthetic rifamycin, was 2-10 times more active in vitro than rifampicin (RAMP) against several clinical isolates of Mycobacterium tuberculosis and only slightly less active than RAMP against Gram-positive and Gram-negative bacteria. It showed excellent therapeutic activity in mice in experimental infections caused by Staphylococcus aureus, Streptococcus pyogenes group A, Streptococcus pneumoniae and Klebsiella pneumoniae. In the experimental TB infection in the mouse DL 473 was clearly more active than isoniazide and RAMP, two of the most effective antitubercular drugs in current use. The LD50 in the mouse was significantly higher than that of RAMP and the half-life was about 5 times longer than that of RAMP.