Bactericidal Activity of Streptomycin and Isoniazid Against Tubercle Bacilli

Abstract

MBwIrc JOURNAL (Barnett et al., 1953b) and in rabbits (Domagk, quoted by Klee, 1953) it would seem probable that they would be of low virulence in man. However, patients in the Medical Research Council (1952) trials who developed resistant strains (growth on Lowenstein slopes containing 1 pAg. of isoniazid per ml.) benefited less from treatment with isoniazid than did those whose strains remained sensitive. There seem to be three possible explanations for the apparent contradiction. In the first place, even the most highly resistant strains set up large abscesses at the site of inoculation and usually mninimal regressive lesions in the spleen, liver, or lungs. Thus these strains are not com- pletely avirulent. Secondly, when strains from patients appear highly resistant in sensitivity tests there may be bacilli with a lower degree of resistance, and therefore higher virulence, in areas of the lungs containing progres- sive tuberculous lesions. Thirdly, the virulence of resistant strains may be increased by treatment with isoniazid; this may have occurred in the guinea-pigs infected with strains *L, H, and Fy, although the numbers of animals were too small to allow a firm conclusion. It has also been reported in mice in three out of four experiments (Barnett et al., 1953b).