Isonicotinic Acid Hydrazide (Rimifon) in the Treatment of Tuberculosis

Abstract

SUMMARY An investigation has been carried out to determine the efficacy of isoniazid (Rimifon) in a series of 25 tuberculous patients. Beginning in March 1952, 13 were maintained under sanatorium regime and 12 were ambulant cases seen at the out-patient service of the San Angel Sanatorium in Mexico City. Clinical trial over a 90-day period indicates that the drug is almost non-toxic in human beings at a daily dosage of 4 milligrams per kilogram of body weight. Further clinical observations in one patient using a routine dosage of 8 milligrams per kilogram of body weight for a period longer than 90 days, seem to indicate that the drug is also well tolerated on this higher dosage schedule. The drug was noted to produce a marked euphroic effect. In the hospitalized group symptomatic response in the majority of patients was excellent as evidenced by increase in appetite, rapid gain in weight, tendency toward normal temperature, diminished cough and improved character of the sputum. In only five of the 12 hospitalized cases with positive sputum cultures at the beginning of therapy were consistently negative cultures obtained by the end of the treatment period. The hematological changes are consistent with the shifting of the immunobiological response of the body to the tuberculous infection. Roentgenological changes were slow in developing in the few cases in which they were evident. Examination of the films taken at the end of 90 days of treatment shows the beginning of change in some of the cases not previously exhibiting an improvement. Some patients completely failed to respond to the drug. There is the possibility of a correlation between failure to respond to isoniazid and previous history of spontaneous or acquired resistance to chemically related drugs such as the thiosemicarbazones. The results in the ambulatory patients in the series were less satisfactory indicating the need for bed rest and an adequately controlled regime in the treatment program. In evaluating these results consideration should be given to the fact that in this series the hospitalized patients had not responded to any other procedures and were critically ill at the time treatment was started. Four of the patients were practically moribund and in three of these cases the drug proved to be life-saving. The fourth patient responded initially but then regressed. It was felt that her life was prolonged about four months because of the drug. While uniform results were not obtained so far as the degree of response is concerned, isoniazid provided a most effective therapy for the severely ill tuberculous patients in the series.