Gardner Middlebrook

Infectivity, pathogenicity and sulpholipid fraction of some Indian and British strains of tubercle bacilli

Summary A highly significant correlation has been established between ‘infectivity among a group of strains of Myco. tuberculosis of British and Indian origin for tho-guinea pig and the yield of sulpholipid fraction from these strains cultivated in vitro .

Effect of para-aminosalicylic acid on serum isoniazid levels in man.

Summary A method for the microbiologic assay of INH in the presence of high concentrations of streptomycin or PAS is described. The concurrent oral administration of PAS with INH resulted in detectable elevation of the antimicrobially active INH level in the blood serum of 22 of 25 tuberculous patients. The significance of this effect is discussed.

Experimental penicillin prophylaxis of staphylococcal infection in rabbits.

Summary Experimental wound infections with small inocula of staphylococci were regularly produced in rabbits. Prophylactic penicillin was effective in preventing such experimental wound infections due to “penicillin-resistant” staphylococci when size of inoculum was small and when the infecting organisms were derived from environment containing no penicillin. Under similar conditions penicillin was not effective in preventing wound infection due to small inocula of “penicillin-resistant” staphylococci which were derived from an environment containing penicillin. The authors acknowledge technical assistance of Charmion Carnes.

Dosages of isoniazid and streptomycin for routine chemotherapy of tuberculosis.

Summary The importance of adjusting the dosage of isoniazid and of streptomycin administered to tuberculous patients so that at least a 0·4 μg./ml. serum level of isoniazid and 20 μg./ml. serum level of streptomycin be concomitantly achieved is discussed. The results of microbiologic assays for antimicrobially active isoniazid and streptomycin serum levels in a group of 1,010 tuberculous patients are presented. About 30 per cent of a group of 744 patients failed to achieve the estimated minimal isoniazid level consistent with total sterilization of all multiplying catalase-positive (isoniazid-susceptible and weakly isoniazid-resistant) tubercle bacilli after a loading dose of 4 mg. isoniazid per kg. body weight; the increase of the loading dose to 8 mg. isoniazid per kg. body weight still left 20 per cent of a group of 633 patients with a serum level below 0·4 μg./ml. The loading dose was calculated as half the total projected daily dosage of isoniazid. Thirty per cent of a group of 501 patients failed to achieve the estimated necessary serum level (20μg./ml. serum) six hours after an intramuscular injection of 20 mg. streptomycin sulfate per kg. body weight. It is concluded that the only way to assure an optimal isoniazid and streptomycin concentration at the sites of bacterial multiplication in tuberculous patients without increasing unnecessarily the incidence of toxic side-effects is to ‘tailor’ these drugs dosages according to the individual patients metabolic rate of inactivation of isoniazid and renal clearance of streptomycin. These rates can be determined by properly performed microbiologic assays for antimicrobially active serum isoniazid and streptomycin concentrations.

The treatment of primary tuberculosis in infancy.

Summary 1. The management of the infant under one year with primary pulmonary tuberculosis has received inadequate attention in the past. 2. The malignant forms of progressive primary tuberculosis, i.e., miliary tuberculosis and tuberculous meningitis, occur with greatest frequency during infancy, and should be prevented whenever possible. 3. All infants and children should routinely be tested with tuberculin in order to detect early the presence of primary tuberculosis. 4. BCG should be given to those likely to be exposed to tuberculosis. 5. Infants with a positive tuberculin and negative x-ray findings should receive a course of INH. 6. Infants with a positive tuberculin and positive x-ray findings should receive INH and streptomycin sulfate.

Attenuation of isoniazid-resistant mutants of tubercle bacilli and host hypersensitivity to tuberculin.

Summary Isoniazid-resistant, catalasedeficient strains of tubercle bacilli are strikingly less pathogenic for hamsters than for CF1 mice. Neither of these species of animals manifests much tuberculin hypersensitivity. Therefore, the differences in susceptibility of different animal species to such strains of tubercle bacilli cannot be consistently related to differences in ability to develop tuberculin hypersensitivity during the course of tuberculous infection.

Comparison of freeze-dried daughter strains of BCG by aerogenic immunization and virulent challenge

Summary Experimental aerogenic infection of guinea pigs with small numbers of bacterial cells from freeze-dried BCG vaccine preparations has revealed that one preparation was greatly superior to four others. It was shown that killing guinea pigs three weeks after challenge, with virulent tubercle bacilli by aerogenic infection provides a rapid test of the efficacy of an immunizing agent. A strong correlation of a positive tuberculin reaction with immunity following aerogenic vaccination with small numbers of BCG was demonstrated.