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ISONIAZID IN THE TREATMENT OF PULMONARY TUBERCULOSIS.*

By BRENDAN O'BRIEN.

I t tAVE been asked to start the discussion on the use of isoniazid by considering the indications for the use of this drug. When the lay press, a year ago, burst into headlines, over this miraculous new treat-

ment, I think we must have all felt sceptical about its merits, but time and trials would appear to have substantiated quite a reasonable pro- portion of the early claims.

The report of the Medical Research Council of England suggests that it is almost as potent as streptomycin and P.A.S. combined, and that by Joiner and others from Guy's Hospital, while not confirming this fully, also shows a very marked degree of efficacy.

The trials have nearly all been held on patients with fairly advanced disease on the whole, and I have myself used it in only a comparatively small number of cases. Only 22 received isoniazid alone, others have had it combined with streptomycin, which is too small a group from which to form any useful conclusion. All my patients were given 4 mgm. per kilogram body weight. Amongst these 22 patients, three were cases of minimal tuberculosis diagnosed on x-ray appearances only. Of these, two were treated with the drug alone and showed no significant weight increase nor any improvement which could not be attributed to rest alone; the third was much under weight and was treated by artificial pneumothorax, isoniazid being given in the hopes of improving his very poor appetite. There was no increase in appetite or in weight.

The next group of four patients all had cavities. One was acutely ill following a h~emoptysis; his treatment was supplemented with pneumo- peritoneum and that of another with pneumothorax, but all four were potentially good eases. In all, the cavities closed and the sputum became and remained negative.

The remainder were all advanced eases with bilateral cavitation. One had a weight increase of 42 lbs., but continued to have small cavities and a positive sputum with drug-resistant organisms. One, a married woman, was going steadily downhill on streptomycin, and had pyrexia to 101 ° F. in spite of treatment ; after the administration of isoniazid her tempera- ture and sedimentation rate gradually fell, her weight increased slightly and she felt considerably better, but slowly relapsed to her previous con- dition. Another married woman had high pyrexia with bilateral cavita- tion and extensive bronehopneumonie disease with very distressing cough : she made a dramatic improvement as regards cough and tempera- ture after the administration of isoniazid. A man of 65, a chronic alcoholic, who looked almost moribund when first seen, showed very little improvement after six weeks' treatment with streptomycin; he made a dramatic improvement shortly after starting on isoniazid. He had been so thin that it had become impossible to give him injections of strepto-

Opening paper to Symposium at Section of Medicine, 19th December, 1952.

266 IRISH JOURNAL OF MEDICAL SCIENCE

mycin, yet he put on 25 lbs. in five weeks. His improvement continued until he was able to walk again; he then suffered a coronary thrombosis, but he is still alive. Another man of 60, with chronic long-standing fibrotic disease with cavitation in both lungs and a gastric ulcer, did not put on any significant amount of weight though he felt somewhat better, but his sputum became negative and was still negative 220 days after the beginning of treatment. The remaining cases all became negative for a time, but all became again positive after varying intervals.

On the whole, I have found that the appetite has been improved in about half my patients, though there were only two who showed that strikhlg weight increase for which the ori~nal communications made such strong claims. Those with the most acute disease, especially those with broncho-pneumonia, have shown the most striking benefit.

I should, therefore, consider that isoniazid may be used in cases where deterioration is taking place in spite of streptomycin therapy or in those with streptomycin-resistant organisms; in any acute bronchopneumonic cases if combined with streptomycin ; in any case combined with collapse therapy. In these, it is, of course, impossible to assess the value of the drug, as so many patients do very well on collapse therapy alone.

In view of the findings with regard to resistance, isoniazid should probably never be used alone nor in cases whose cavities are liable to remain open. It may be used as a measure of desperation when all else fails, to prolong life, if not to arrest disease. It does not seem to have any marked effect on minimal lesions and, therefore, might well be held in reserve in case such lesions should eventually break down. The drug is so cheap and so well tolerated, and can so easily be administered in the home, that one is tempted to regard its indications as the poet re- garded those for drink, when he declared:

If all be true that I do think, There are five reasons we should drink: Good wine--a friend--or being d ry - - Or lest we should be, by and by-- Or any other reason why!

but this temptation should be resisted and the drug be reserved for those cases where it is likely to do lasting good, or help the patient who is otherwise untreatable. I t should never be regarded as a substitute for proper sanatorium treatment.