The Value of Streptomycin in the Treatment of Tuberculosis

Abstract

A brief and incomplete summary of the beginning and development of Streptomycin work over the world, including important features of our own work, has been presented. The essential features may be enumerated as follows: Streptomycin “suppresses” the growth of practically all strains of tubercle bacilli for periods of several weeks to several months. During that period of time there is a large number of cases changed from poor to a good prognosis; this will be reflected ultimately in a lowered death rate and a shortening of the time of individual convalescence. Resistance to Streptomycin develops partially or completely in about 80 per cent of strains of tubercle bacilli on or before 120 days of treatment. Recently formed lesions (probably those retaining blood circulation) respond the most favorably to treatment with Streptomycin; lesions respond less favorably as they become more caseous or more fibroid in character. At the present time, indications are that the optimum dosage of Streptomycin is around one gram a day, although 0.5 of a gram a day has been used with success. In our work we have used a dosage regimen of 0.5 gram a day on adult patients under 150 pounds, and 0.75 gram a day on those over 150 pounds, for 45 to 120 days or up to the time of development of bacilliary resistance. In infants and children under 50 pounds 0.1 to 0.3 grams has been found adequate. Only one case of labyrinth disease has developed on this regimen. Of 863 cases in which treatment was completed, using the 0.5 to 0.75 gram dosage, 470 cases (54.5 per cent) were improved in a substantial and more or less permanent way; have gone on to recovery; are progressing towards recovery; or have undergone surgery. There were 670 (77.6 per cent of all cases) non-surgical cases, 425 of which were pulmonary (63.3 per cent of the latter group and 49.3 per cent of all cases). Of these pulmonary cases, 223 (52.5 per cent of the group and 25.9 per cent of all cases) were improved. Of the remainder of the non-surgical cases, 245 (28.3 per cent of all cases) were non-pulmonary, with 148 (60.4 per cent of the latter and 17.2 per cent of all cases) showed improvement. Surgery was recommended in 193 (22.4 per cent of all treated) cases, of which 99 have been operated on successfully and 28 have been operated on but have had postoperative complications; 66 cases have refused surgery or the operation has been delayed for one reason or another. On meningeal, miliary, bone, joint and genito-urinary lesions, 1.0 to 1.5 grams of Streptomycin is still recommended, but Dihydrostreptomycin in doses up to two grams is preferred because of its lower neuro-toxicity. The basic pathologic change in the tubercle is in the reduction ion of monocytes and epitheloid cells; the decrease and perhaps cessation of caseation with a gradual fibrotic replacement of the central caseation and a thickening of the capsule of the tubercle. In primary calcified tubercles there is a marked acceleration of calcification and resorption of the calcification with replacement by fibroblasts, collagenous tissue and capillaries. In the lesions of the intestinal mucosa where the epithelium is largely destroyed, the first changes observed are the disappearance of acute inflammatory cells and a withering of the epithelioid and giant cells from the floors of the ulcers with only a few lymphocytes remaining. Later changes have not yet been observed, but it is presumed that fibroblasts and fibrocytes appear in order and ultimate re-epithelialization takes place. The types of lesions in the central nervous system are quite varied, depending on many factors such as the type of the disease, duration of the disease before treatment, the development of fibrous tissue, and development of bacilliary resistance. In partly healed lesions fibrous tissue may block the subarachnoid spaces, causing hydocephalus; basalar endarteritis and endophlebitis may lead to white and red encephalomalacia respectively. Small tubercles may heal by fibrosis as do lesions elsewhere in the body or there may be exacerbations of caseous and fibrocaseous lesions in the meninges, mostly in its basal region. There is nothing specific in the pathologic changes caused by Streptomycin.