A Controlled Comparison of a Twice-Weekly and Three Once-Weekly Regimens in the Initial Treatment of Pulmonary Tuberculosis

value of a fully supervised twice-weekly regimen of high-dosage isoniazid plus streptomycin in the treatment of newly diagnosed tuberculous patients with drug-sensitive cultures. A logical consequence of this finding was an investigation of regimens with a longer interval between successive doses. The present report describes the findings of a controlled study of 3 once-weekly regimens and the twice-weekly regimen. The results confirm that the twice-weekly regimen is highly effective and demonstrate that its efficacy is not influenced by the rate of inactivation of isoniazid or by a reduction (by one-fourth) in the dosage of streptomycin. The results also show that once-weekly chemotherapy from the beginning, whether with high-dosage isoniazid plus streptomycin or high-dosage isoniazid plus streptomycin plus high-dosage pyrazinamide, gives unsatisfactory results. However, when an initial daily phase of 4 weeks with a moderate dosage of isoniazid plus streptomycin preceded the once-weekly phase of high-dosage isoniazid plus streptomycin, the response was highly satisfactory in slow inactivators of isoniazid (as good as with the twice-weekly regimen) but was considerably less satisfactory in rapid inactivators. These findings suggest that if a method of compensating for the insufficiency of this regimen in rapid inactivators of isoniazid can be found, the prospects for evolving a highly satisfactory once-weekly regimen are bright

A Concurrent Comparison of Intermittent (Twice-Weekly) Isoniazid plus Streptomycin and Daily Isoniazid plus PAS in the Domiciliary Treatment of Pulmonary Tuberculosis

Previous reports from the Tuberculosis Chemotherapy Centre, Madras, have established that ambulatory treatment of pulmonary tuberculosis with the combination of isoniazid and PAS, administered daily, yields satisfactory results. However, in the usage of any unsupervised regimen, reliance must be placed on the co-operation of patients in self-administering their drugs. Irregularities in drug-taking, which are not uncommon, may lead to unfavourable therapeutic results; this might be avoided by supervised administration of the drugs. Daily supervision is clearly impracticable in developing countries but regimens in which the drug is administered intermittently-say, twice a week or less frequently-are, if effective, more likely to gain general application. This paper presents the results of a controlled study of a fully supervised intermittent regimen of isoniazid (12.5-16.1 mg/kg body-weight, orally) plus streptomycin (injected in a uniform dose of I g), given together twice weekly, compared with a standard, unsupervised, daily, oral regimen of isoniazid (3.7-63 mg/kg body-weight) plus sodium PAS (0.2-0.3 g/kg body-weight), given in two doses. The intermittent regimen was at least as effective as the standard oral regimen, and although the incidence of temporary giddiness in patients receiving this regimen was rather high, this did not appear to have any long-term importance nor did it appear unduly to affect the co-operation of the patients. These encouraging findings suggest a possible change in the orientation of drug-administration for tuberculosis in developing countries

A Concurrent Comparison of Isoniazid plus PAS with Three Regimens of Isoniazid Alone in the Domiciliary Treatment of Pulmonary Tuberculosis in South India

Recent studies have shown that treatment of pulmonary tuberculosis with isoniazid plus p-aminosalicylic acid (PAS) at home is, in the majority of cases, as satisfactory as treatment with the same combination of drugs in sanatorium and does not appear to expose the patient’s contacts to any special risk. Before mass domiciliary chemotherapy can be introduced, however, a question that has to be decided is what drug or drugs and what dosage and rhythm of administration will be most effective. This paper presents the results of a controlled comparison of four chemotherapeutic regimens : (a) 3.9-5.5 mglkg body-weight of isoniazid plus 0.2-0.3 g/kg body-weight of PAS (sodium salt) daily in two doses (the standard combined chemotherapy) ; (b) 7.8-9.6 mglkg body-weight of isoniazid alone daily in one dose ; (c) 7.8-9.6 mg/kg body-weight of isoniazid alone daily in two doses ; (d) 3.9-5.5 mg/kg body-weight of isoniazid alone daily in two doses. Isoniazid plus PAS proved to be the most satisfactory regimen; it was clinically effective and there were very few toxic manifestations

Controlled Comparison of Oral Twice-weekly and Oral Daily Isoniazid plus PAS in Newly Diagnosed Pulmonary Tuberculosis

A controlled clinical trial was undertaken in 247 patients with newly diagnosed pulmonary tuberculosis to assess the relative efficacies of a fully supervised twice-weekly oral regimen of isoniazid plus PAS (para-aminosalicylic acid) and a standard self-administered daily regimen of the same drugs following an initial intensive phase of two weeks of daily streptomycin, PAS, and isoniazid. Among patients who had isoniazid-sensitive cultures initially and who attended the clinic regularly the numbers with a favourable bacteriological response at the end of the year of chemotherapy were 79 (88%) out of 90 for the twice-weekly regimen and 72 (87%) out of 83 for the daily regimen; the numbers of patients with considerable radiographic improvement were 54 (60%) and 53 (64%) respectively. Complaints of vomiting or diarrhoea that did not require a reduction of the PAS dosage were made on one or two occasions by 23 (21 % ) out of 109 twice-weekly and 25 (23%) out of 108 daily patients, and on at least three occasions by 4 (4%) and 12 (11%) respectively. Finally, all five patients who had chemotherapy changed on account of hypersensitivity to PAS had been receiving the daily regimen, as also had one patient who died of agranulocytosis

Isoniazid plus Thioacetazone * compared with Two Regimens of Isoniazid plus PAS in the Domiciliary Treatment of Pulmonary Tuberculosis in South Indian Patients

Previous reports from the Tuberculosis Chemotherapy Centre, Madras, have established that ambulatory treatment of pulmonary tuberculosis with a standard daily regimen of isoniazid plus PAS for one year yields satisfactory results. However, this regimen may be unsuitable for large-scale use in many developing countries, because PAS is expensive, bulky and unpleasant to take, and has poor keeping qualities, especially in tropical countries. It might be possible to overcome these disadvantages, by substituting for the PAS a drug which is equally effective but less expensive and more acceptable, or by reducing the daily dosage of PAS and the period for which it is prescribed. This paper presents the results over a II-month period of a controlled comparison of (a) the standard regimen of isoniazid (average 4.5 mg/kg body-weight) plus sodium PAS (average 0.22 g/kg), daily in two divided doses ; (b) a regimen of isoniazid (average 6.9 mg/kg) plus thioacetazone (average 3.4 mg/kg), daily in one dose ; and (c) a 2-phase regimen of isoniazid (average 5.5 mg/kg) plus sodium PAS (average 0.17 g/kg), daily in one dose for 6 months, followed by isoniazid alone (average 6.8 mg/kg), daily in one dose for the second 6 months. The regimen of isoniazid plus thioacetazone was found to be therapeutically as effective as the standard regimen of isoniazid plus PAS ; however, it was associated with a higher incidence of minor side-effects, and three cases of exfoliative dermatitis. The 2-phase regimen of isoniazid plus PAS followed by isoniazid alone was less effective. These findings are encouraging for the large-scale use in developing countries of the relatively inexpensive regimen of isoniazid plus thioacetazone ; however, any such step should be preceded by carefully planned studies to investigate, under local conditions, the toxicity and the efficacy of the regimen

A Concurrent Comparison of Home and Sanatorium Treatment of Pulmonary Tuberculosis in South India

In India, as in most under-developed countries, the tuberculosis problem is aggravated by an acute shortage of sanatorium beds. The number of active cases of tuberculosis in the country has been estimated at 2 ½ million, but only 23 000 tuberculosis beds are available. In these circumstances great importance attaches to the possibility of applying mass domiciliary chemotherapy as a substitute for sanatorium treatment in cases of pulmonary tuberculosis. The findings of the present study,, based on a comparison of the two types of treatment over a period of 12 months, show that despite the manifest advantages of sanatorium care—rest, adequate diet, nursing and supervised medicine-taking-the merits of domiciliary chemotherapy are comparable to those of sanatorium treatment, and that it would therefore be appropriate to treat the majority of patients at home, provided an adequate service were established

Intermittent treatment of pulmonary tuberculosis: a concurrent comparison of twice-weekly isoniazid plus streptomycin and daily isoniazid plus p-aminosalicylic acid in domiciliary treatment

DOMICILLIARY chemotherapy of tuberculosis has become accepted practice in developing countries, but the best method of administering the drugs is still in question. Self-medication for long periods may result in irregularities, and, although fully supervised daily chemotherapy has been used to avoid these, it imposes a considerable strain on clinic and patients, and is hardly practicable in developing countries (see review by Fox 1). If, instead, supervised therapy could be given intermittently–e.g., twice a week–the method could become more generally applicable

The prevention and treatment of isoniazid toxicity in the therapy of pulmonary tuberculosis : 1. An assessment of two vitamin B preparations and glutamic acid.

This paper from the Tuberculosis Chemotherapy Centre, Madras, presents the results of a study designed primarily (a) To assess the efficacy of two preparations-Tab. Ancurin, Co, (a vitamin B compound not containing pyridoxine) and glutamic acid-in preventing the development of peripheral neuropathy during high-dosage (12.5-15.2 mg/kg) isoniazid therapy for pulmonary tuberculosis, and (b) to compare the therapeutic efficacy, once isoniazid neuropathy has developed, of Tab. Aneurin, Co., administered at twice the prophylactic dosage, and a vitamin-B-complex preparation containing a small amount of pyridoxine (amounting to 6 mg daily). Tab. Aneurin, Co., was found to be ineffective in preventing peripheral neuropathy, which occurred in five of the 18 patients receiving this preparation, as compared with six of the 18 who received a placebo, calcium gluconate. Glutamic acid appeared to have some prophylactic effect, since only two of the 19 patients receiving it developed the neuropathy, but the difference between the frequency in the glutamic series and that in the placebo series did not attain statistical significance. As to the therapeutic efficacy of the two vitamin B preparations, Tab. Aneurin, Co., at twice the prophylactic dosage, did not prevent the progression of the neuropathy in five out of seven patients, whereas improvement occurred in eight of the nine patients who received the vitamin-B-complex preparation containing the small amount of pyridoxine. This study has confirmed that the frequency of peripheral neuropathy is significantly higher among slow than among rapid inactivators of isoniazid and has indicated that the therapeutic response of the tuberculosis is not materially affected by increasing the dosage of isoniazid from 7.8-9.6 mg/kg. (the dosage used in a previous study) to 12.5-15.2 mg/kg