Tuberc Respir Dis.  1970 Dec;17(4):17-28. 10.4046/trd.1970.17.4.17.

Antimicrobial Activity of Rifampicin in Vitro and in Established Tuberculosis in Mice

• KMID: 2529117
• DOI: http://doi.org/10.4046/trd.1970.17.4.17

Abstract

A study was made of antimicrobial activity of rifampicin in vitro against 31 clinical isolates from Korean TB patients without previous antituberculous chemotherapy. Also the strains were tested. the standard strain H₃₇Rv, M. bovis, M. avium and 6 strains of mycobacteria other than M. tuberculosis including 11 additional strains of Gram-positive and Gram-negative bacteria. Also studied in vivo were the therapeutic effects of rifampicin on established tuberculosis mice. Mice weighing 14±1 gm were inoculated intravenously with M. tuberculosis (H₃₇Rv). The treatment was oral and the foIlowing drugs were given daily, isoniazid (10 mg per kg), rifampicin (10 mg per kg), and isoniazid (5 mg per kg) combined with rifampicin (10 mg per kg). The results obtained are as the foIlowings. 1) Of the 27 strains tested on Lowenstein-Jensen medium, aIl 27 were inhibited by 10 mcg/ ml concentration, 23 were inhibited by 5 mcg/ml concentration, and 12 were inhibited by 2. 5 mcg/ ml concentration. 2) Of the 31 strains tested in Kirschner’s medium, 23 strains were inhibited at 1 mcg/ ml concentration, 10 strains were inhibited at 0.5 mcg/ml concentration, and 4 strains were inhibited at 0. 1 mcg/ ml concentration. AIl 31 strains were resistant at 0.05 mcg/ ml. 3) Of the 31 strains tested in Dubos broth medium, all 31 were sensitive at 1 mcg/ ml concentration, while 30 strains, 26 strains, 21 strains, and 1 strains showed sensitiveness at 0. 5 mcg/ ml, and 0. 1 mcg/ ml, 0. 05 mcg/ ml, and 0. 01 mcg/ ml concentrations respectively. 4) Incidence of naturaIly resistant mutants in the H₃₇Rv of M. tuberculosis was 20 per 10⁴ bacilli at 5 mcg/ ml and 66 per 10⁸ bacilli at 10 mcg/ml concentrations on L-J medium after 6 weeks incubation. 5) The strains of M. bovis, M. thamnopheos, Photochromogen and Scotochromogen showed remarkable susceptibility but M. avium and M. platypoecilus showed a growth even at 20 mcg/ml concentration. 6) In an additional study of Gram-positive and Gram-negative bacteria susceptibility to rifampicin, Gram-negative strains showed resistance at 1 mcg/ ml concentration while Gram-positive' strains were inhibited at 0. 05 mcg/ml concentration. 7) After 10 weeks of therapy for established tuberculosis in mice, the combination of isoniazid with rifampicin was most effective, and isoniazid alone, next effective, and rifampicin alone, least effective on the basis of reduction of viable units in lung. But there was no significant differences among the three regimens in death rate, lung-body weight ratio, spleen-bcdy weight ratio, and Aoki’s standard observation of lung lesions. 8) The strains reisolated from established tuberculosis mice did not show resistance to rifampicin during the 10 weeks therapy.