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REPORT OF THE COMMITTEE ON CHEMOTHERAPY AND ANTIBIOTICS
REPORT OF THE COMMITTEE ON CHEMOTHERAPY
AND ANTIBIOTICS
Streptomycin is the most valuable and encouraging agent yet to be developed for the treatment of tuberculosis. After extensive animal experimentation and observation of its clinical use in several thousand patients, certain definite statements may be made. While much clinical investigation remains to be done, streptomycin may now be accepted as a valuable and at times necessary adjunct in the treatment of certain types of tuberculosis. The optimum dally dose, frequency of administration, and duration of treatment with streptomycin for tuberculosis have not yet been fully established. The accumulated evidence indicates that for an adult 1 gram dally in divided doses given every 6 to 8 hours for 75 to 100 days may be sufficient in many cases. Some recent evidence indicates that a therapeutic dose may be as low as 0.25 gram given as infrequently as once a day. The drug is best given intramuscularly or by deep subcutaneous injection, but not intravenously. in solutions containing 100 to 250 mg. of streptomycin per c.c. Excretion is chiefly in the urine. There is a certain toxicity, and undesirable side reactions may occur. No deaths have been reported resulting from the use of streptomycin. In general, the reactions are mild and even when severe are not sufficient to interfere with treatment of patients with progressive tuberculosis which is not amenable to other therapy. There is some question, because of these side reactions, whether streptomycin should be used in the treatment of patients who would respond satisfactorily to more conventional forms of therapy. Disturbance of equillbrium due to loss of vestibular function is the most common of these reactions. There is a definite correlation between dosage of streptomycin and this vestibular disorder, which will occur in most of the cases receiving 2 grams or more per day for any long period of time; whereas, administration of 1 gram per day for the same period will cause no such disorder in more than half of the patients so treated. Evidence of sensitization: chills, fever, nausea, and cutaneous rashoccurs occasionally within the first few weeks of treatment. The administration of the drug should be discontinued in such a case; and after a few days when the symptoms have subsided, the patient should be desensitized with dally doses commencing at 50 to 100 mg. and increased gradually to the customary therapeutic dose. Streptomycin is essential in the treatment of tuberculous meningitis, miliary tuberculosis, tuberculosis of the larynx, trachea and bronchi, draining sinuses from tuberculous infection of bones and glands, and tuberculosis of the intestinal tract. Caution and clinical judgment are required in the treatment of pulmonary tuberculosis with this agent. Not all cases are suitable for this treatment. Old chronic fibrocaseous lesions and thick-walled cavities are not usually affected much, if any, by this drug. Recently developed pneumonic and exudative lesions show the best response; recent and thin-walled cavities may close or show decrease in size. . The greatest use of streptomycin is as an adjunct to the more customary methods of treating pulmonary tuberculosis. The clinician should plan to combine streptomycin with collapse therapy, pulmonary resection, or whatever is indicated to produce a satisfactory result. 718
Volumexm
COLLEGE NEWS
719
The factor which interfere£,~t,.,eriously with prolonged treatment with streptomycin is the developmEmt of streptomycin resistant strains of tubercle bac1lll. This apparently occurs most frequently during the third or fourth month of treatment, and may limit the effectiveness of the treatment to that period. In many of these cases, subsequent treatment with streptomycin will be found to be ineffective. Some work is being done on combination of streptomycin with other substances which may aid in postponing the development of resistant strains. It should be remembered that streptomycin cannot imp~ove irreversible destructive tissue changes and, in general, cannot replace surgical treatment. It can and does widen the indications for surgical treatment by reducing toxicity, diminishing the tendency of the disease to spread, and causing resolution of many recent exudations. It can thus improve the patient's status to the point where surgical treatment may be done with greater safety and better end results. streptomycin is not a cure-all nor even a real cure. It will not replace sanatorium or hospital care nor substitute for accepted treatment in most cases. However, the time has come to state that its value has been established and that it has a definitely recognized place in the treatment of tuberculosis. It should be available to all patients in whom its use is a necessary or important adjunct to their recovery. For this reason an item covering the cost of this drug should be included in the annual budgets of all institutions established for, or undertaking the treatment of, tuberculosis. Karl H. Pfuetze, M.D., F.C.C.P., Chairman, Subcommittee on Chemotherapy and Antibiotics Edwin R. Levine, M.D., F.C.C.P., Chairman, Committee on Management and Treatment of Diseases of the Chest Committee on Chemotherapy and Antibiotics:
Karl H. Pfuetze, M.D., Cannon Falls, Minnesota, Chairman B. L. Freedlander, M.D., San Francisco, California, Vice-Chairman Sumner S. Cohen, M.D., St. Louis Park, Minnesota, secretary Manuel Albertal, M.D., Buenos Aires, Argentina Arnold Shamaskin, M.D., Hines, nIinois Carl W. Tempel, coi., M.C., Denver, Colorado John V. Thompson, M.D., Indianapolis, Indiana
AND ANTIBIOTICS
Streptomycin is the most valuable and encouraging agent yet to be developed for the treatment of tuberculosis. After extensive animal experimentation and observation of its clinical use in several thousand patients, certain definite statements may be made. While much clinical investigation remains to be done, streptomycin may now be accepted as a valuable and at times necessary adjunct in the treatment of certain types of tuberculosis. The optimum dally dose, frequency of administration, and duration of treatment with streptomycin for tuberculosis have not yet been fully established. The accumulated evidence indicates that for an adult 1 gram dally in divided doses given every 6 to 8 hours for 75 to 100 days may be sufficient in many cases. Some recent evidence indicates that a therapeutic dose may be as low as 0.25 gram given as infrequently as once a day. The drug is best given intramuscularly or by deep subcutaneous injection, but not intravenously. in solutions containing 100 to 250 mg. of streptomycin per c.c. Excretion is chiefly in the urine. There is a certain toxicity, and undesirable side reactions may occur. No deaths have been reported resulting from the use of streptomycin. In general, the reactions are mild and even when severe are not sufficient to interfere with treatment of patients with progressive tuberculosis which is not amenable to other therapy. There is some question, because of these side reactions, whether streptomycin should be used in the treatment of patients who would respond satisfactorily to more conventional forms of therapy. Disturbance of equillbrium due to loss of vestibular function is the most common of these reactions. There is a definite correlation between dosage of streptomycin and this vestibular disorder, which will occur in most of the cases receiving 2 grams or more per day for any long period of time; whereas, administration of 1 gram per day for the same period will cause no such disorder in more than half of the patients so treated. Evidence of sensitization: chills, fever, nausea, and cutaneous rashoccurs occasionally within the first few weeks of treatment. The administration of the drug should be discontinued in such a case; and after a few days when the symptoms have subsided, the patient should be desensitized with dally doses commencing at 50 to 100 mg. and increased gradually to the customary therapeutic dose. Streptomycin is essential in the treatment of tuberculous meningitis, miliary tuberculosis, tuberculosis of the larynx, trachea and bronchi, draining sinuses from tuberculous infection of bones and glands, and tuberculosis of the intestinal tract. Caution and clinical judgment are required in the treatment of pulmonary tuberculosis with this agent. Not all cases are suitable for this treatment. Old chronic fibrocaseous lesions and thick-walled cavities are not usually affected much, if any, by this drug. Recently developed pneumonic and exudative lesions show the best response; recent and thin-walled cavities may close or show decrease in size. . The greatest use of streptomycin is as an adjunct to the more customary methods of treating pulmonary tuberculosis. The clinician should plan to combine streptomycin with collapse therapy, pulmonary resection, or whatever is indicated to produce a satisfactory result. 718
Volumexm
COLLEGE NEWS
719
The factor which interfere£,~t,.,eriously with prolonged treatment with streptomycin is the developmEmt of streptomycin resistant strains of tubercle bac1lll. This apparently occurs most frequently during the third or fourth month of treatment, and may limit the effectiveness of the treatment to that period. In many of these cases, subsequent treatment with streptomycin will be found to be ineffective. Some work is being done on combination of streptomycin with other substances which may aid in postponing the development of resistant strains. It should be remembered that streptomycin cannot imp~ove irreversible destructive tissue changes and, in general, cannot replace surgical treatment. It can and does widen the indications for surgical treatment by reducing toxicity, diminishing the tendency of the disease to spread, and causing resolution of many recent exudations. It can thus improve the patient's status to the point where surgical treatment may be done with greater safety and better end results. streptomycin is not a cure-all nor even a real cure. It will not replace sanatorium or hospital care nor substitute for accepted treatment in most cases. However, the time has come to state that its value has been established and that it has a definitely recognized place in the treatment of tuberculosis. It should be available to all patients in whom its use is a necessary or important adjunct to their recovery. For this reason an item covering the cost of this drug should be included in the annual budgets of all institutions established for, or undertaking the treatment of, tuberculosis. Karl H. Pfuetze, M.D., F.C.C.P., Chairman, Subcommittee on Chemotherapy and Antibiotics Edwin R. Levine, M.D., F.C.C.P., Chairman, Committee on Management and Treatment of Diseases of the Chest Committee on Chemotherapy and Antibiotics:
Karl H. Pfuetze, M.D., Cannon Falls, Minnesota, Chairman B. L. Freedlander, M.D., San Francisco, California, Vice-Chairman Sumner S. Cohen, M.D., St. Louis Park, Minnesota, secretary Manuel Albertal, M.D., Buenos Aires, Argentina Arnold Shamaskin, M.D., Hines, nIinois Carl W. Tempel, coi., M.C., Denver, Colorado John V. Thompson, M.D., Indianapolis, Indiana