The effect of some penicillins on Mycobacterium tuberculosis.

Five clinical isolates of Mycobacterium tuberculosis and the standard H37Rv strain were tested in vitro for susceptibility to six penicillins. Cloxacillin was clearly the most active antimicrobial drug tested, and at a concentration of 10 mug/ml it had a striking bactericidal effect on five of the strains. Several combinations of penicillins (oxacillin plus benzylpenicillin, and 6 aminopenicillanic acid plus either benzylpenicillin or ampicillin) showed synergistic effects. Sequential assay of antimicrobial activity in medium incubated for more than 21 days showed a significant decay that was accelerated when growing mycobacteria were present. When daily additions of antimicrobial drug were made to compensate for spontaneous or mycobacteria mediated drug inactivation, much lower concentrations of antimicrobial drug were inhibitory. Thus, recognition of antimicrobial instability in the testing system and compensating for it showed that cloxacillin inhibited most strains in vitro at a concentration readily achieved in man.