1887

Abstract

Summary

The sensitivity of three strains of to dapsone (DDS) and rifampicin (RMP), administered continuously in the diet, was determined in the mouse footpad system. All three strains were inhibited by 0.0001 per cent. DDS. Sensitivity to RMP varied, the minimum inhibitory dose (MID) being 0.001 per cent, for two strains and 0.0003 per cent, for the third.

During the administration of 0.01 per cent. RMP, the concentrations of RMP in mouse serum, estimated by microbiological assay, was relatively constant at about 6 pg per ml over a 66-day period. The considerations for assuming a linear relationship between dietary dosage and the resultant serum concentration are discussed. It is inferred that a minimum inhibitory dose of RMP for of 0.001 per cent, is equivalent to a minimum inhibitory concentration for the organism of 0.3 μg per ml.

The bactericidal action of DDS and of RMP on M. leprae was assessed by means of the kinetic technique of Shepard. The DDS treatment used apparently had no significant bactericidal effect. The bactericidal action of RMP was found to be relatively high, confirming the previous finding of Rees in patients with lepromatous leprosy. Complete killing of was obtained after 30 days’ treatment with 0.01 per cent. RMP in the diet (equivalent to a serum concentration of about 5 μg per ml). The relationship between the concentration of RMP in the serum of mice and its bactericidal action on appears to be very similar to the corresponding relationship found in patients treated with the drug.

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1972-05-01
2024-04-19
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References

  1. Brouet J. H., Modai J., Vergez P. 1969; Essais cliniques de la rifampicine en monotherapie. Etude des taux seriques. Revue Tuberc 33:27
    [Google Scholar]
  2. Constans P., Saint-Paul M., Morin Y., Bonnaud G., Bariety M. 1968; Rifampicine: première étude des dosages plasmatiques au cours de traitements prolonges chez des tuberculeux pulmonairés. Revue Tuberc 32:991
    [Google Scholar]
  3. Dickinson Jean M., Mitchison D. A. 1966; In vitro studies on the choice of drugs for intermittent chemotherapy of tuberculosis. Tubercle, Lond 47:370
    [Google Scholar]
  4. Gaugas J. M. 1967; Antimicrobial therapy of experimental human leprosy (Myco. leprae) infection in the mouse foot pad. Lepr. Rev 38:225
    [Google Scholar]
  5. Grumbach F., Rist N. 1967; Activite antituberculeuse experimentale de la rifampicine derive de la rifamycine SV. Revue Tuberc 31:749
    [Google Scholar]
  6. Hilson G. R. F., Banerjee D. K., Holmes I. B. 1972 The activity of various antituberculous drugs in suppressing experimental Mycobacterium leprae infection in mice. Int. J. Lepr in press;
    [Google Scholar]
  7. Hilson G. R. F., Elek S. D. 1957; Intratesticular multiplication of Mycobacterium lepraemurium in normal and suramin-treated animals. Int. J. Lepr 25:380
    [Google Scholar]
  8. Nitti V., Catena E., Bariffi F., Delle Veneri F. 1967; L’attività terapeutica della rifampicina nella tubercolosi polmonare. Arch. Tisiol 22:417
    [Google Scholar]
  9. Pallanza R., Arioli V., Furesz S., Bolzoni G. 1967; Rifampicin: a new rifamycin. II Laboratory studies on the antituberculous activity and preliminary clinical observations. Arzneimittel-Forsch 17:529
    [Google Scholar]
  10. Porven G., Canetti G. 1968; Les taux de rifampicine dans le serum de l’homme. Revue Tuberc. 32:707
    [Google Scholar]
  11. Rees R. J. W. 1965; Recent bacteriologie, immunologie and pathologie studies on experimental human leprosy in the mouse foot pad. Int. J. Lepr 33:646
    [Google Scholar]
  12. Rees R. J. W. 1967; Drug resistance of Mycobacterium leprae, particularly to DDS. Int. J. Lepr 35:625
    [Google Scholar]
  13. Rees R. J. W., Valentine R. C. 1962; The appearance of dead leprosy bacilli by light and electron microscopy. Int. J. Lepr 30:1
    [Google Scholar]
  14. Rees R. J. W., Pearson J. M. H., Waters M. F. R. 1970; Experimental and clinical studies on rifampicin in treatment of leprosy. Br. Med. J 1:89
    [Google Scholar]
  15. Shepard C. C. 1960; The experimental disease that follows the injection of human leprosy bacilli into foot-pads of mice. J. Exp. Med 112:445
    [Google Scholar]
  16. Shepard C. C. 1967a; A kinetic method for the study of activity of drugs against Mycobacterium leprae in mice. Int. J. Lepr 35:429
    [Google Scholar]
  17. Shepard C. C. 1967b; Activity of repository sulfones against Mycobacterium leprae in mice. Proc. Soc. Exp. Biol. Med 124:430
    [Google Scholar]
  18. Shepard C. C. 1969a; Further experience with the kinetic method for the study of drugs against Mycobacterium leprae in mice. Activities of DDS, DFD, ethionamide, capreo-mycin and PAM 1392. Int. J. Lepr 37:389
    [Google Scholar]
  19. Shepard C. C. 1969b; Minimal effective dosages in mice of clofazimine (B 663) and of ethionamide against Mycobacterium leprae. Proc. Soc. Exp. Biol. Med 132:120
    [Google Scholar]
  20. Shepard C. C., Chang Y. T. 1962; Effect of several antileprosy drugs on multiplication of human leprosy bacilli in foot-pads of mice. Proc. Soc. Exp. Biol. Med 109:636
    [Google Scholar]
  21. Shepard C. C., Chang Y. T. 1964; Activity of antituberculosis drugs against Mycobacterium leprae. Studies with experimental infection of mouse footpads. Int. J. Lepr 32:260
    [Google Scholar]
  22. Shepard C. C., Chang Y. T. 1967; Effect of DDS on established infections with Mycobacterium leprae in mice. Int. J. Lepr 35:52
    [Google Scholar]
  23. Shepard C. C., McRae Dorothy H., Habas Janet A. 1966; Sensitivity of Mycobacterium leprae to low levels of 4,4′-diaminodiphenyl sulfone. Proc. Soc. Exp. Biol. Med 122:893
    [Google Scholar]
  24. Verbist L., Gyselen A., Cosemans J., Prignot J. 1967; Preliminary results with rifampicin in the retreatment of multiresistant pulmonary tuberculosis in ten salvage cases. Proc. Vth Int. Congr. Chemother. (Vienna) edited by Spitzy K. H., and Haschek H. II/2:591
    [Google Scholar]
  25. Waters M. F. R., Rees R. J. W. 1962; Changes in the morphology of Mycobacterium leprae in patients under treatment. Int. J. Lepr 30:266
    [Google Scholar]
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