Experimental models to explain the high sterilizing activity of rifampin in the chemotherapy of tuberculosis

Abstract

Model systems were set up in vitro to explore the reasons why rifampin is a better sterilizing drug than isoniazid in short-course chemotherapy of tuberculosis. When the growth rate of Mycobacterium tuberculosis strain H37Rv was reduced uniformly by lowering the incubation temperature or the pH of the culture medium, the bactericidal activity of rifampin and isoniazid decreased to a similar extent. However, when a culture was maintained at 8 degrees C and incubated for daily periods of 1 or 6 h at 37 degrees C, rifampin killed more rapidly than isoniazid. Maintenance of control cultures without antimicrobials at 8 degrees C with or without periods at 37 degrees C, had little or no effect on their viability, ability to commence logarithmic growth at 37 degrees C, or to incorporate [14C]uridine. Old cultures left undisturbed or to which small additions of fresh culture medium were regularly added were killed more rapidly by rifampin than by isoniazid. These experiments supported the view that the special part of the bacterial population that is killed more rapidly by rifampin than by isoniazid during short-course chemotherapy consists of bacilli dormant much of the time but occasionally metabolising for short periods.