rifampin and ranbezolid

The decision to develop a new chemical entity should not only be based on its ability to inhibit multidrug-resistant tuberculosis (MDR-TB) strains but also on its ability to enter macrophages and be active against intracellular bacteria. RBx 7644 and RBx 8700, two novel extended spectrum oxazolidinones, were investigated for their activity against sensitive and MDR isolates of Mycobacterium tuberculosis and for activity against bacteria within a macrophage cell line. RBx 8700 showed excellent in vitro activity against sensitive as well as MDR M. tuberculosis strains with MIC(50) and MIC(90) values of 0.032 and 0.25mg/L (sensitive) and 0.25 and 1.0mg/L (MDR) strains. The corresponding MIC(50) and MIC(90) values of RBx 7644, linezolid, rifampicin and isoniazid were 8 and 16; 32 and 64; 64 and 64; 64 and 64 mg/L, respectively. RBx 8700 and rifampicin were bactericidal at 0.5 and 0.25mg/L when tested intracellularly whereas linezolid reduced the count by 100-fold at a concentration of 8 mg/L. In combination studies with standard antimycobacterial drugs, RBx 8700 did not show any antagonistic effect.

Topics: Acetamides; Animals; Antitubercular Agents; Cell Line; Drug Antagonism; Furans; Isoniazid; Linezolid; Macrophages; Mice; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; Oxazoles; Oxazolidinones; Rifampin