In vitro and in vivo evaluation of L/105, a new topical intestinal rifamycin.

L/105 (4-deoxy-4'-methylpyrido [1',2'-1,2] imidazo [5,4-c] rifamycin SV; INN: Rifaximin) is a new rifamycin active in vitro against both gram-positive and gram-negative microorganisms. The activity of L/105 was comparable to that of rifampicin and, against gram-positive bacteria, higher than that of neomycin. The antibacterial activities of L/105 and rifampicin were equally affected by the highest size of inoculum used (10 cells/ml) and they were equally bactericidal against Staphylococcus aureus and Escherichia coli. The speed and the degree of development of resistance to L/105 were quite superimposable on those of neomycin. In vivo, L/105 did not show therapeutic activity by oral route in the staphylococcal infection in the mouse till the highest dosage used (10 mg/kg b.w.); under the same conditions, gentamicin was equally ineffective. After subcutaneous administration, L/105 showed therapeutic activity (ED50 = 0.46 mg/kg b.w.) practically superimposable on that of orally administered rifampicin.