Evaluation of the activity of a number of antimicrobial agents against mycobacteria within mouse macrophages by a radiometric method.

[3H]-uridine was incorporated by Mycobacterium bovis BCG with increasing intensity as the incubation period was increased. Rifampicin and isoniazid inhibited incorporation of the label rapidly. Similar inhibition was seen with M. tuberculosis H37Rv and several clinical isolates of M. tuberculosis both in axenic medium and inside macrophages. Ofloxacin and ciprofloxacin were both inhibitory but clofazimine was not. The combination of rifampicin with either isoniazid or ethambutol produced enhanced killing, but the combination of ethambutol and isoniazid was not synergic. Mycobacterium avium-intracellulare isolates from AIDS patients were less susceptible to rifampicin and were unaffected by isoniazid, ethambutol, clofazimine, ofloxacin and ciprofloxacin. The results obtained by inhibition of [3H]-uridine incorporation by intracellular mycobacteria correlated with conventional in-vitro MICs and was reproducible and rapid; a definitive result was obtainable within seven days.