Factors influencing the outcome of streptomycin therapy of pulmonary tuberculosis.

1) The experience of the cooperative study by the Veterans Administration, Army and Navy of the effects of streptomycin in the treatment of tuberculosis has been briefly reviewed. This investigation has been one primarily of the influence of varying dosage regimens in quite uniform clinical material. It has shown that dosages of 1 gram a day are therapeutically effective, with an incidence of toxic manifestations sufficiently low not to be a serious handicap. It has shown that regimens of 42-day and 60-day duration, while not quite as effective as those of longer duration, are preferable to the latter because of definitely lower incidence of emergence of streptomycin-resistant tubercle bacilli. 2) The method of reporting data in the study of the Veterans Administration, Army and Navy has permitted relatively little evaluation of variables of therapy other than those of regimen. To a limited extent the study has indicated that results are superior when streptomycin and collapse therapy are employed in combination; that disease which is progressive before initiation of streptomycin therapy improves more than stationary disease; and that moderately advanced disease improves more than minimal or far-advanced disease, in comparable periods of time. 3) The experience of the Minneapolis Veterans Administration Hospital with the streptomycin therapy of cases of pulmonary tuberculosis is presented. The material consists of 86 cases of active disease, 57 cases treated according to the Veterans Administration protocol for pulmonary tuberculosis, and 29 cases of less extensive disease treated primarily for extra-pulmonary tuberculosis. 4) All cases had a definitely acute or subacute inflammatory tuberculous component; a proportion of these had clear-cut mixtures of both chronic disease and more recent disease. This “mixed” group of cases was found to have an outcome of therapy definitely inferior to that of the “relatively unmixed” acute and subacute cases, in all categories studied. It is believed that it is important to stress this classification in the evaluation of the results of streptomycin therapy in the treatment of tuberculosis. 5) In the 86 cases, both those treated and not treated on the pulmonary protocol, results were superior when collapse therapy (thoracoplasty in over half the cases collapsed) was employed in close conjunction with the period of maximum benefit from streptomycin therapy, which in general consisted of the first eight months after the start of antibiotic therapy. This was true for both “relatively unmixed” acute and chronic cases and for “mixed” cases, but especially for the latter. These observations appear to be largely independent of variations in the five streptomycin regimens employed. 6) Evidence is presented to indicate that observation of any degree of x-ray improvement, whether slight, moderate or marked, at the end of the initial treatment period, is a method of evaluation which is inadequate for discrimination of results between regimens employed, or between groups of cases treated. It is believed that standardized measures of the degree of x-ray improvement enhance roentgenographic evaluation, particularly in the first months after the start of therapy. Sputum conversion rates and relapse rates are important additional criteria for evaluating results. In later follow-up periods mortality rates are of increasing value. 7) It is concluded that the response of the cavitary component to streptomycin therapy, as to any form of treatment of pulmonary tuberculosis, is the chief factor determining the outcome of a program of therapy in which streptomycin is a part; and that prompt and energetic measures directed toward the control of that component have at present the best opportunity for improving still further the already distinguished achievements of the streptomycin therapy of pulmonary tuberculosis.