Skip to main content
Bulletin of the World Health Organization logoLink to Bulletin of the World Health Organization
. 1970;43(1):143-206, 208.

A controlled comparison of a twice-weekly and three once-weekly regimens in the initial treatment of pulmonary tuberculosis

Tuberculosis Chemotherapy Centre
PMCID: PMC2427666  PMID: 5312317

Abstract

A previous report from the Tuberculosis Chemotherapy Centre, Madras, demonstrated the 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.

Full text

PDF
143

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARMSTRONG A. R., PEART H. E. A comparison between the behavior of Eskimos and non-Eskimos to the administration of isoniazid. Am Rev Respir Dis. 1960 Apr;81:588–594. doi: 10.1164/arrd.1960.81.4.588. [DOI] [PubMed] [Google Scholar]
  2. CANETTI G., FROMAN S., GROSSET J., HAUDUROY P., LANGEROVA M., MAHLER H. T., MEISSNER G., MITCHISON D. A., SULA L. MYCOBACTERIA: LABORATORY METHODS FOR TESTING DRUG SENSITIVITY AND RESISTANCE. Bull World Health Organ. 1963;29:565–578. [PMC free article] [PubMed] [Google Scholar]
  3. DEVADATTA S., BHATIA A. L., ANDREWS R. H., FOX W., MITCHISON D. A., RADHAKRISHNA S., RAMAKRISHNAN C. V., SELKON J. B., VELU S. Response of patients infected with isoniazid-resistant tubercle bacilli to treatment with isoniazid plus PAS or isoniazid alone. Bull World Health Organ. 1961;25:807–829. [PMC free article] [PubMed] [Google Scholar]
  4. DEVADATTA S., GANGADHARAM P. R., ANDREWS R. H., FOX W., RAMAKRISHNAN C. V., SELKON J. B., VELU S. Peripheral neuritis due to isoniazid. Bull World Health Organ. 1960;23:587–598. [PMC free article] [PubMed] [Google Scholar]
  5. Dickinson J. M., Ellard G. A., Mitchison D. A. Suitability of isoniazid and ethambutol for intermittent administration in the treatment of tuberculosis. Tubercle. 1968 Dec;49(4):351–366. doi: 10.1016/s0041-3879(68)80016-9. [DOI] [PubMed] [Google Scholar]
  6. EIDUS L., HAMILTON E. J. A NEW METHOD FOR THE DETERMINATION OF N-ACETYL ISONIAZID IN URINE OF AMBULATORY PATIENTS. Am Rev Respir Dis. 1964 Apr;89:587–588. doi: 10.1164/arrd.1964.89.4.587. [DOI] [PubMed] [Google Scholar]
  7. EVANS D. A., WHITE T. A. HUMAN ACETYLATION POLYMORPHISM. J Lab Clin Med. 1964 Mar;63:394–403. [PubMed] [Google Scholar]
  8. Evans C., Devadatta S., Fox W., Gangadharam P. R., Menon N. K., Ramakrishnan C. V., Sivasubramanian S., Somasundaram P. R., Stott H., Velu S. A 5-year study of patients with pulmonary tuberculosis treated at home in a controlled comparison of isoniazid plus PAS with 3 regimens of isoniazid alone. Bull World Health Organ. 1969;41(1):1–16. [PMC free article] [PubMed] [Google Scholar]
  9. FOX W. Self-administration of medicaments. A review of published work and a study of the problems. Bull Int Union Tuberc. 1962 Jul;32:307–331. [PubMed] [Google Scholar]
  10. Fox W. The John Barnwell Lecture. Changing concepts in the chemotherapy of pulmonary tuberculosis. Am Rev Respir Dis. 1968 May;97(5):767–790. doi: 10.1164/arrd.1968.97.5.767. [DOI] [PubMed] [Google Scholar]
  11. GANGADHARAM P. R., DEVADATTA S., FOX W., NAIR C. N., SELKON J. B. Rate of inactivation of isoniazid in South Indian patients with pulmonary tuberculosis. 3. Serum concentrations of isoniazid produced by three regimens of isoniazid alone and one of isoniazid plus PAS. Bull World Health Organ. 1961;25:793–806. [PMC free article] [PubMed] [Google Scholar]
  12. GILROY A. B. An investigation of proguanil prophylaxis and co-existing parasitaemia. Ann Trop Med Parasitol. 1952 May;46(1):72–84. doi: 10.1080/00034983.1952.11685508. [DOI] [PubMed] [Google Scholar]
  13. GRUMBACH F., CANETTI G., GROSSET J. FURTHER EXPERIMENTS ON LONG-TERM CHEMOTHERAPY OF ADVANCED MURINE TUBERCULOSIS, WITH EMPHASIS ON INTERMITTENT REGIMES. Tubercle. 1964 Jun;45:125–135. doi: 10.1016/s0041-3879(64)80070-2. [DOI] [PubMed] [Google Scholar]
  14. GRUMBACH F. Treatment of experimental murine tuberculosis with different combinations of isoniazid/streptomycin followed by isoniazid alone. Am Rev Respir Dis. 1962 Aug;86:211–215. doi: 10.1164/arrd.1962.86.2.211. [DOI] [PubMed] [Google Scholar]
  15. HOLST E., MITCHISON D. A., RADHAKRISHNA S. Examination of smears for tubercle bacilli by fluorescence microscopy. Indian J Med Res. 1959 Sep;47:495–499. [PubMed] [Google Scholar]
  16. JOHNSTON R. N., SMITH D. H., RITCHIE R. T., LOCKHART W. PROLONGED STREPTOMYCIN AND ISONIAZID FOR PULMONARY TUBERCULOSIS. Br Med J. 1964 Jun 27;1(5399):1679–1683. doi: 10.1136/bmj.1.5399.1679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. KASIK J. E., HELLER A., LESTER W., BARCLAY W. R. A simple spot test to determine whether a patient is taking isoniazid. Am Rev Respir Dis. 1962 Feb;85:282–284. doi: 10.1164/arrd.1962.85.2.282. [DOI] [PubMed] [Google Scholar]
  18. LEE S. H., MCCUNE R. M., Jr, MCDERMOTT W., TOMPSETT R., WASZ-HOCKERT O. Resistance of tubercle bacilli to pyrazinamide in vivo. Am Rev Tuberc. 1956 Oct;74(4):572–580. doi: 10.1164/artpd.1956.74.4.572. [DOI] [PubMed] [Google Scholar]
  19. LLOYD J., MITCHISON D. A. A VERTICAL DIFFUSION METHOD FOR THE MICROBIOLOGICAL ASSAY OF ISONIAZID. J Clin Pathol. 1964 Nov;17:622–626. doi: 10.1136/jcp.17.6.622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lefford M. J., Mitchison D. A., Tall R. Bacteriological aspects of the second national survey of primary drug resistance in pulmonary tuberculosis, 1963. Tubercle. 1966 Mar;47(1):109–129. doi: 10.1016/s0041-3879(66)80054-5. [DOI] [PubMed] [Google Scholar]
  21. MITCHISON D. A. CHEMOTHERAPY OF TUBERCULOSIS: A BACTERIOLOGIST'S VIEWPOINT. Br Med J. 1965 May 22;1(5446):1333–1340. [PMC free article] [PubMed] [Google Scholar]
  22. MITCHISON D. A., SPICER C. C. A method of estimating streptomycin in serum and other body fluids by diffusion through agar enclosed in glass tubes. J Gen Microbiol. 1949 May;3(2):184–203. doi: 10.1099/00221287-3-2-184. [DOI] [PubMed] [Google Scholar]
  23. MITCHISON D. S. Titration of strains of tubercle bacilli against isoniazid. Lancet. 1952 Nov 1;2(6740):858–860. doi: 10.1016/s0140-6736(52)91743-1. [DOI] [PubMed] [Google Scholar]
  24. McDERMOTT W., TOMPSETT R. Activation of pyrazinamide and nicotinamide in acidic environments in vitro. Am Rev Tuberc. 1954 Oct;70(4):748–754. doi: 10.1164/art.1954.70.4.748. [DOI] [PubMed] [Google Scholar]
  25. Ramakrishnan C. V., Devadatta S., Evans C., Fox W., Menon N. K., Nazareth O., Radhakrishna S., Sambamoorthy S., Stott H., Tripathy S. P. A four-year follow-up of patients with quiescent pulmonary tuberculosis at the end of a year of chemotherapy with twice-weekly isoniazid plus streptomycin or daily isoniazid plus pas. Tubercle. 1969 Jun;50(2):115–124. doi: 10.1016/0041-3879(69)90018-x. [DOI] [PubMed] [Google Scholar]
  26. Ramakrishnan C. V., Janardhanam B., Krishnamurthy D. V., Stott H., Subbammal S., Tripathy S. P. Toxicity of pyrazinamide, administered once weekly in high dosage, in tuberculous patients. Bull World Health Organ. 1968;39(5):775–779. [PMC free article] [PubMed] [Google Scholar]
  27. Subbammal S., Krishnamurthy D. V., Tripathy S. P., Venkataraman P. Concentrations of pyrazinamide attained in serum with different doses of the drug. Bull World Health Organ. 1968;39(5):771–774. [PMC free article] [PubMed] [Google Scholar]
  28. Tripathy S. P., Menon N. K., Mitchison D. A., Narayana A. S., Somasundaram P. A., Stott H., Velu S. Response to treatment with isoniazid plus PAS of tuberculous patients with primary isoniazid resistance. Tubercle. 1969 Sep;50(3):257–268. doi: 10.1016/0041-3879(69)90050-6. [DOI] [PubMed] [Google Scholar]
  29. VELU S., ANDREWS R. H., ANGEL J. H., DEVADATTA S., FOX W., GANGADHARAM P. R., NARAYANA A. S., RAMAKRISHNAN C. V., SELKON J. B., SOMASUNDARAM P. R. Progress in the second year of patients with quiescent pulmonary tuberculosis after a year of domiciliary chemotherapy, and influence of further chemotherapy on the relapse rate. Bull World Health Organ. 1961;25:409–429. [PMC free article] [PubMed] [Google Scholar]
  30. VELU S., ANDREWS R. H., DEVADATTA S., FOX W., RADHAKRISHNA S., RAMAKRISHNAN C. V., SELKON J. B., SOMASUNDARAM P. R., SUBBAIAH T. V. Progress in the second year of patients with quiescent pulmonary tuberculosis after a year of chemotherapy at home or in sanatorium, and influence of further chemotherapy on the relapse rate. Bull World Health Organ. 1960;23:511–533. [PMC free article] [PubMed] [Google Scholar]
  31. Venkataraman P., Eidus L., Ramachandran K., Tripathy S. P. A comparison of various methods for the detection of isoniazid and its metabolites in urine. Tubercle. 1965 Sep;46(3):262–269. doi: 10.1016/s0041-3879(65)80020-4. [DOI] [PubMed] [Google Scholar]

Articles from Bulletin of the World Health Organization are provided here courtesy of World Health Organization

RESOURCES