ACTION OF METRONIDAZOLE IN COMBINATION WITH ISONIAZID AND RIFAMPICIN ON PERSISTING ORGANISMS IN EXPERIMENTAL MURINE TUBERCULOSIS

To study the activity of metronidazole on persisting tubercle bacilli, BALB/c mice were infected with Mycobacterium tuberculosis and, after 14 days, treated with isoniazid (H) or rifampicin (R) or isoniazid + r ifampicin (HR) for 2 months. An untreated group and a group treated wi th metronidazole (M) alone served as controls. At the end of 2 months, M was added to the H, R, and HR regimen in half the mice, and the tre atment was continued for 1 more month in all mice. At the end of treat ment, no viable organisms were detected in the lung or spleen of mice treated with HR or HRM regimens. In contrast, compared to the mice tre ated with R alone, the log(10) colony forming units (cfu) of mice trea ted with RM were lower by 1.84 and 0.52 in the lung and spleen, respec tively. Similarly, compared to the H group, the log(10) cfu were lower by 0.67 in the spleen of mice treated with HM, and no additional effe ct due to M was seen in the lung. Three months after stopping treatmen t, viable organisms were isolated from both the organs of all the grou ps. However, the log(10) cfu in the lung and spleen for the groups wit h metronidazole were below the log(10) cfu for the respective single o r 2 drug groups, except the log(10) cfu in the lung for the RM group. These findings suggest that metronidazole, given with bactericidal dru gs such as rifampicin and isoniazid may be of value in eliminating per sisting tubercle bacilli, but further studies are warranted.