THE EMERGENCE OF ISONIAZID-RESISTANT CULTURES IN PATIENTS WITH PULMONARY TUBERCULOSIS DURING TREATMENT WITH ISONIAZID ALONE OR ISONIAZID PLUS PAS.

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  • Additional Information
    • Source:
      Publisher: World Health Organization Country of Publication: Switzerland NLM ID: 7507052 Publication Model: Print Cited Medium: Print ISSN: 0042-9686 (Print) Linking ISSN: 00429686 NLM ISO Abbreviation: Bull World Health Organ Subsets: OLDMEDLINE
    • Publication Information:
      Original Publication: Geneva : World Health Organization,
    • Subject Terms:
      Aminosalicylic Acid* ; Aminosalicylic Acids* ; Drug Resistance* ; Drug Resistance, Microbial* ; Drug Therapy* ; Isoniazid* ; Mycobacterium* ; Research* ; Tuberculosis, Pulmonary*; Humans ; India
    • Abstract:
      Previous reports from the Tuberculosis Chemotherapy Centre, Madras, have described a comparison of four regimens (three of isoniazid alone and one of isoniazid plus PAS) in the treatment of pulmonary tuberculosis and an investigation of the serum isoniazid levels in the patients concerned. The present report studies the emergence of isoniazid-resistant organisms in these patients during treatment. All patients with an unsatisfactory response to treatment yielded resistant cultures, showing that the isoniazid dosage was never too low to inhibit sensitive organisms. From the degree of resistance of the first resistant cultures and of the six-month cultures from the patients treated with isoniazid alone it was concluded that resistance emerged in two stages. In the first stage, very earlyin treatment, highly resistant mutant bacilli grew freely whatever the isoniazid dosage, but mutants of lower resistance were prevented from growing to an extent dependent on the peak isoniazid concentration in the serum. Consequently, when the isoniazid dosage was increased the proportion of patients with resistant organisms decreased, since fewer low-resistance strains were able to develop. In the second stage, organisms with relatively low resistance continued to multiply, though still partially inhibited by isoniazid, and became more resistant, particularly in slow inactivators. The first-stage events determined the results of treatment since, once resistance had emerged, its extent was unrelated to the patient's eventual progress. These findings emphasize the importance of early intensive chemotherapy and adjustment of the isoniazid dosage according to peak serum concentrations rather than concentrations measured three or six hours after the dose. Concomitant administration of PAS prevented emergence of isoniazid resistance in many patients and in others delayed its emergence and reduced its degree, possibly because growth in the second stage was slow.
    • References:
      Am Rev Respir Dis. 1963 Feb;87:269-75. (PMID: 13994580)
      Ann Inst Pasteur (Paris). 1961 Jul;101:28-46. (PMID: 13690427)
      Thorax. 1955 Jun;10(2):85-98. (PMID: 14396842)
      Aust J Exp Biol Med Sci. 1958 Jun;36(3):223-33. (PMID: 13596269)
      Bull World Health Organ. 1961;25:793-806. (PMID: 13896635)
      Bull World Health Organ. 1961;25:409-29. (PMID: 13925282)
      Am Rev Tuberc. 1954 Nov;70(5):784-92. (PMID: 13207631)
      Bull World Health Organ. 1961;25:779-92. (PMID: 13910443)
      Am Rev Tuberc. 1952 Jun;65(6):765-7. (PMID: 14924201)
      Bull World Health Organ. 1961;25:765-77. (PMID: 13896634)
    • Contributed Indexing:
      Keywords: AMINOSALICYLIC ACID*; DRUG RESISTANCE, MICROBIAL*; DRUG THERAPY*; EXPERIMENTAL LAB STUDY*; ISONIAZID*; MYCOBACTERIUM*; TUBERCULOSIS, PULMONARY*
    • Accession Number:
      0 (Aminosalicylic Acids)
      5B2658E0N2 (Aminosalicylic Acid)
      V83O1VOZ8L (Isoniazid)
    • Publication Date:
      Date Created: 19640101 Date Completed: 19961201 Latest Revision: 20181201
    • Publication Date:
      20231215
    • Accession Number:
      PMC2555166
    • Accession Number:
      14253244