[Therapeutic efficacy of kanamycin and clofazimine combined with muramyl dipeptide against Mycobacterium intracellulare infection induced in mice].
Therapeutic efficacy of kanamycin (KM) and clofazimine (CFZ) combined with N2-[(N-acetyl-muramyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-ly sine, MDP-Lys (L18), against Mycobacterium intracellulare infection induced in mice was studied, based on suppression of incidence of gross lung lesions and bacterial growth at the sites of infection (lungs and spleen), and the following results were obtained. Firstly, KM (0.5 mg) was given sc to mice, daily six times per week in combination (or not) with sc injections of MDP-Lys(18) (0.1 mg) either 1, 3 or 5 times weekly. In this case, KM alone markedly suppressed the incidence of pulmonary gross lesions and the growth of organisms in the lungs and spleen (2-2.5 log-decrease in CFU per organ at week 8) in infected mice. MDP-Lys(18) alone also exhibited similar effect but the efficacy was much lower than that of KM. No synergism was observed for combined use of KM with MDP-Lys(18) in any protocols tested. Secondly, CFZ (0.5 mg) was given to mice by gavage, daily six times per week in combination with or without injections of MDP-Lys(18) (0.1 mg), either 1, 3 or 5 times weekly. In this case, CFZ alone decreased the incidence of gross pulmonary lesions in infected mice and the weaker suppressive effect was noted for MDP-Lys(18) alone. Moreover, CFZ alone suppressed bacterial growth in the lungs and spleen (1.5-2.0 log-decrease in CFU per organ at week 8), while MDP alone failed to cause such a marked reduction in bacterial CFU in the visceral organs.(ABSTRACT TRUNCATED AT 250 WORDS)
Tomioka
H
H
Department of Microbiology and Immunology, Shimane Medical University, Izumo, Japan.
Sato
K
K
Saito
H
H
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002991:Clofazimine / Q000008:administration & dosage / Q000627:therapeutic use*; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D007612:Kanamycin / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D009162:Mycobacterium avium; D014376:Tuberculosis / Q000188:drug therapy*
D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007612:Kanamycin; D002991:Clofazimine