We compared the activities of two different
biological-response modifiers with that of
clarithromycin against Mycobacterium avium complex
infection in C57BL/6 mice. Mice were pretreated daily with
clarithromycin (50 mg/kg of
body weight subcutaneously [s.c.]),
RU-40555 (100 mg/kg s.c.), or
granulocyte colony-stimulating factor (
G-CSF) at low dose (15 micrograms/kg intraperitoneally [i.p.]) or high dose (300 micrograms/kg i.p.) 3 days before intravenous challenge with 2.5 x 10(7) CFU of the MO-1 strain of M. avium complex. Mice were treated daily until sacrifice at day 1, 8, 15, or 21 after challenge, and the numbers of CFU were measured per gram of tissue in lung and spleen. Compared at day 21 with control treatment,
clarithromycin significantly decreased the level of
infection in spleen (P < 0.0001) and lungs (P < 0.0001). Compared with control treatment,
G-CSF at low dose had no activity, but
G-CSF in combination with
clarithromycin was more effective than
clarithromycin alone in spleen (P < 0.05) and lungs (P < 0.015). The high dose of
G-CSF was as effective as the low dose.
RU-40555 alone had no beneficial activity. The RU-40555-clarithromycin combination was more effective than control treatment in spleen (P = 0.0001) and lungs (P < 0.0005) and more effective than
clarithromycin alone in spleen (P < 0.009) but not in lungs. Thus, our experiments suggest that
clarithromycin alone or in combination with
G-CSF should be further evaluated for the prophylaxis of M. avium complex
infection.