Cycloserine-Isoniazid Combination Therapy in Virgin Cases of Pulmonary Tuberculosis

¹ The Departments of Medicine and Pulmonary Diseases, New York Medical College, Metropolitan Medical Center.

1. New, previously untreated cases of pulmonary tuberculosis were treated with a cycloserine-isoniazid combination given orally.

2. Eighty-one cases have been treated for from six weeks to 16 months, with but a single reaction, which did not necessitate discontinuance of treatment.

3. Clinical improvement, reduction of fever, lessening of the volume of sputum, and gain in weight occurred promptly in every case. In addition, the administration of a single capsule containing cycloserine and isoniazid, twice daily, was more acceptable to the patients than the usual INHPAS combination.

4. Within six weeks, 40 per cent of the x-ray films showed evidence of improvement. The figure rose to 74 per cent in 12 weeks, and to 93 per cent of 48 subjects treated for six months.

5. Evidence of reduction in the bacillary content of the sputum was [see table in source pdf] obtained within six weeks of treatment. Within three months, 80 per cent of 64 sputa were negative on culture, and at six months the figure rose to 87 per cent.

6. Bacillary sensitivity to cycloserine fell slowly and slightly during prolonged treatment with the larger doses. From 0.5 Gm. of cycloserine per day, there was no evidence of decreased sensitivity.

7. Resistance to INH developed during the administration of the cycloserine isoniazid combination at approximately the same rate as is seen when INH is given alone.

8. It is our conclusion that a combination of 0.25 Gm. of cycloserine and 0.15 Gm. of INH given twice daily is effective and safe therapy against previously untreated cases of pulmonary tuberculosis. We feel that our clinical results were superior to the usual INH-PAS therapy, both in speed and degree of response, as gauged by x-ray film changes and sputum conversion.

Acknowledgments: We are grateful to Michael G. Mulinos, M.D., Medical Director of Commercial Solvents Corporation, for supplies of cycloserine and for the valuable help and advice he has rendered throughout this investigation. We are also grateful to Mrs. Ann Griffith and to Mr. Abraham Berelson for their valuable technical help.