ABSTRACT
Three hundred and seven clinical isolates of mycobacteria from humans, either susceptible or resistant to one or more antituberculous drugs, were found uniformly susceptible to rifampin, 5ug per ml, in Lowenstein-Jense medium. The incidence of naturally resistant mutants in the H37Rv strain of M. tuberculosis was low (+ or - 10(-8)). Resistance of the single-step type emerged with an 8- to 16-fold increase of the inhibition limit. After 3 weeks of therapy of established tuberculosis in mice, rifampin (5mg per kg) was as effective as isoniazid (5mg per kg) on the basis of mean survival time. The mean of counts of live bacilli, made at intervals during long-term therapy with rifampin (10 mg per kg and 20 mg per kg) for established tuberculosis infection in mice, decreased from 10(8) to 10 (1-2) per lung, completely sterilized lungs were observed in 2 or 3 of the 4 mice sacrified at various intevals. Strains resistant to rifampin were isolated from the lungs of mice treated with rifampin alone: addition of a low dose of isoniazid (2 mg per kg) prevented the emergence of bacilli resistant to rifampin. With 450 mg and 600 mg of rifampin, administered in a single dose an empty stomach in humans, mean peak concentrations of rifampin in the blood of about 7ug per ml were obtained one and one-half hours after drug administration. Rifampin in the blood remained detectable in the blood remained detectable in the blood of all subjects after 9 hours and , in 4 of 12 subjects, after 12 hours as well.