Action of metronidazole in combination with isoniazid & 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 + rifampicin (HR) for 2 months. An untreated group and a group treated with 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 treatment was continued for 1 more month in all mice. At the end of treatment, no viable organisms were detected in the lung or spleen of mice treated with HR or HRM regimens. In contrast, compared to the mice treated with R alone, the log10 colony forming units (cfu) of mice treated with RM were lower by 1.84 and 0.52 in the lung and spleen, respectively. Similarly, compared to the H group, the log10 cfu were lower by 0.67 in the spleen of mice treated with HM, and no additional effect due to M was seen in the lung. Three months after stopping treatment, viable organisms were isolated from both the organs of all the groups. However, the log10 cfu in the lung and spleen for the groups with metronidazole were below the log10 cfu for the respective single or 2 drug groups, except the log10 cfu in the lung for the RM group. These findings suggest that metronidazole, given with bactericidal drugs such as rifampicin and isoniazid may be of value in eliminating persisting tubercle bacilli, but further studies are warranted