Pyrazinamide sterilizing activity in vitro against semidormant Mycobacterium tuberculosis bacterial populations

Previously, we reported that pyrazinamide has very poor bactericidal activity against M. tuberculosis growing in broth at pH 5.6. In the present study, cultivation at pH 4.8 to 5.0 in 7H12 broth prevented an increase in the number of viable bacteria, but the cultures remained metabolically active. The presence of 50 micrograms/ml pyrazinamide in semidormant cultures led to a sharp decline in the number of viable bacteria, by more than 1,000-fold. This unfavorable environment probably made the bacilli especially vulnerable to pyrazinamide, whose mode of action remains unclear. To distinguish this effect of pyrazinamide on the semidormant bacteria from its mostly bacteriostatic activity against actively multiplying bacteria, we suggest interpreting the in vitro effect as "sterilizing."