1887

Abstract

SUMMARY: Isoniazid inhibited the oxidation of acetate in the Warburg apparatus by B.C.G. and other mycobacteria but not by any of the other organisms tested. This effect was investigated in more detail with B.C.G. Inhibition of acetate oxidation was obtained by isoniazid whatever medium had been used for growth. The amount of isoniazid required for inhibition was related to the number of organisms present and their sensitivity to isoniazid as measured by the usual test-tube method. None of the substances reported to antagonize isoniazid inhibition was effective in annulling inhibition by isoniazid in this acetate oxidation system. The effect of various mixtures of drugs on acetate oxidation was tested. Concentrations of isoniazid and streptomycin which when used singly were insufficient to inhibit acetate oxidation, were inhibitory when used together. Similarly, mixtures of isoniazid + -aminosalicylic acid (P.A.S.) or terramycin, or of strepto-mycin + P.A.S., at concentrations which were subinhibitory when used singly, were also effective in inhibiting acetate oxidation. It is suggested that the action of drugs or drug mixtures could usefully be investigated by this or similar techniques which have the advantage of largely eliminating the selection of resistant strains.

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1956-04-01
2021-07-29
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References

  1. Albert A., Rees C.W. 1955; The destruction of iso-nicotinic acid hydrazide in the presence of haemin. Biochem. J. 61:129
    [Google Scholar]
  2. Cohn M.L., Oda U., Kovitz C., Middlebrook G. 1954; Studies on isoniazid and tubercle bacilli. I. The isolation of isoniazid-resistant mutants in vitro. Amer. Rev. Tuberc. 70:465
    [Google Scholar]
  3. Fisher M.W. 1954a; Haemin as a growth factor for certain isoniazid-resistant strains of Mycobacterium, tuberculosis. Amer. Rev. Tuberc. 69:797
    [Google Scholar]
  4. Fisher M.W. 1954b; Antagonism of the tuberculostatic action of isonicotinic acid hydrazide by haemin. Amer. Rev. Tuberc. 69:469
    [Google Scholar]
  5. Gray C.T. 1953; Nature of the action of isonicotinic acid hydrazide on the mycobacteria. Proc. VI Congr. int. Microbiol. 1:179
    [Google Scholar]
  6. Joiner C.L., Maclean K.S., Pritchard E.K., Anderson K., Collard P., King M.B., Knox R. 1952; Isoniazid in pulmonary tuberculosis. Its use with and without streptomycin. Lancet ii:843
    [Google Scholar]
  7. Joiner C.L., Maclean K.S., Chalmers D.G., Anderson K., Collard P., King M.B., Knox R. 1953; Chemotherapy of pulmonary tuberculosis. Lancet ii:152
    [Google Scholar]
  8. Knox R., Albert A., Rees C.W. 1955; Destruction of isoniazid in the presence of haemin. Nature; Lond.: 1751085
    [Google Scholar]
  9. Knox R., Woodroffe R.C. 1955; Haemin-isoniazid interaction and the effect of haemin in ‘reviving’ isoniazid-treated tubercle bacilli. Brit. J. exp. Path. 36:425
    [Google Scholar]
  10. Lascelles J. 1955; The conversion of δ-aminolaevulinic acid to porphyrins by photosynthetic bacteria. J. gen. Microbiol. 12:i
    [Google Scholar]
  11. Meadow P. 1956; The action of isonicotinic acid hydrazide on the metabolism of Mycobacterium smegmatis. J. gen. Microbiol. 14:414
    [Google Scholar]
  12. Medical Research Council 1952; The treatment of pulmonary tuberculosis with isoniazid. Brit. med. J. ii735
    [Google Scholar]
  13. Medical Research Council 1953a; Isoniazid in the treatment of pulmonary tuberculosis. Brit. med. J. i521
    [Google Scholar]
  14. Medical Research Council 1953b; Isoniazid in combination with streptomycin or with P.A.S. in the treatment of pulmonary tuberculosis. Brit. med. J. ii:1005
    [Google Scholar]
  15. Middlebrook G., Cohn M.L., Schaefer W.B. 1954; Studies on isoniazid and tubercle bacilli. III. The isolation, drug susceptibility and catalase testing of tubercle bacilli from isoniazid-treated patients. Amer. Rev. Tuberc. 70:852
    [Google Scholar]
  16. Pitillo R.F., Foster J.W. 1954; Potentiation of inhibitor action through determination of reversing metabolites. J. Bact. 67:53
    [Google Scholar]
  17. Shemin D. 1948; The biosynthesis of porphyrins. Cold Spr. Harb. Symp. quant. Biol. 13:185
    [Google Scholar]
  18. Stewart S.M., Turnbull F.W.A., Crofton J.W. 1954; The use of oxytetra-cycline in preventing or delaying isoniazid-resistance in pulmonary tuberculosis. Brit. med. J. ii:1508
    [Google Scholar]
  19. Tarshis M.S., Kinsella P.C., Parker M.V. 1953; Blood media for the cultivation of Mycobacterium tuberculosis.VIII. Comparison of blood-agar-penicillin and Loewenstein-Jensen media under routine diagnostic conditions. J. Bact. 66:448
    [Google Scholar]
  20. Williams W.L., Broquist H.P., Snell E.E. 1947; Oleic acid and related compounds as growth factors for lactic acid bacteria. J. biol. Chem. 170:619
    [Google Scholar]
  21. Yoneda M., Asano N. 1953; Pyridoxal antagonism of I.N.II. action on decarboxylase of E. coli communius. Science, 117:277
    [Google Scholar]
  22. Yoneda M., Kato N., Okajima M. 1952; Competitive action of isonicotinic acid hydrazide and vitamin B6 in the formation of indole by E. coli. Nature; Lond.: 170803
    [Google Scholar]
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