The Use of Oxytetracycline in Preventing or Delaying Isoniazid Resistance in Pulmonary Tuberculosis

Stewart, Sheila M.; Turnbull, Frank; Crofton, John

doi:10.1136/bmj.2.4903.1508

Cited by 21 publications

(4 citation statements)

References 9 publications

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“…The effective mixtures of drugs in the treatment of certain types of pulmonary tuberculosis appear to be : isoniazid + streptomycin, streptomycin + P.A.S., isoniazid + P.A.S. (Joiner et al 1952(Joiner et al , 1953Medical Research Council, 1952, 1953a, b) ; isoniazid + terramycin (Stewart, Turnbull & Crofton, 1954). These are also the mixtures which are effective in the Warburg apparatus.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Isonicotinic Acid Hydrazide on the Oxidative Metabolism of Mycobacterium tuberculosis var. bovis B.C.G.

Meadow

Knox

1956

Journal of General Microbiology

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SUMMARY : Isoniazid inhibited the oxidation of acetate in the Warburg apparatus by Mycobacterium tuberculosis 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 substancy 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 + p-aminosalicylic acid (P.A.S.) or terramycin, or of streptomycin + 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.In a previous communication (Meadow, 1956) the effect of isonicotinic acid hydrazide (isoniazid) in inhibiting the oxidative metabolism of Mycobacterium smegmatis was described. To show any such inhibition, however, it was necessary to use high concentrations of isoniazid and carefully defined experimental conditions. Further experiments were therefore undertaken with an organism initially about 100 times more sensitive to isoniazid than M . smegmatis. The organism used was the attenuated strain M . tuberculosis var. bovis B.C.G. METHODS Organisms usedMycobacterium tuberculosis var. bovis B.C.G. This was originally obtained from Dr R. J. W. Rees (National Institute for Medical Research, Mill Hill, London, N.W. 7). The parent strain was inhibited by 0.07pg. isoniazid/ml.; and an isoniazid-resistant variant, obtained by serial transfer from the highest concentration of isoniazid in which growth occurred into higher concentrations, grew in 5-1Opg. isoniazid/ml. The strains were maintained in Dubos fluid medium, and subcultured at fortnightly intervals.Mycobacterium smegmatis NCTC 523. The strain was maintained on nutrient agar and subcultured into Dubos fluid medium 24 hr. before use. It was inhibited by 8pg. isoniazid/ml.

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Section: Discussionmentioning

confidence: 99%

The Effect of Isonicotinic Acid Hydrazide on the Oxidative Metabolism of Mycobacterium tuberculosis var. bovis B.C.G.

Meadow

Knox

1956

Journal of General Microbiology

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“…(3) Tetracyclines have previously been recommended in combination with other drugs for the treatment of tuberculous infections (Miller, Sands, Gregory, Hightower, Weiser, and Tempel, 1954;Stewart, Turnbull, and Crofton, 1954;Goth, 1964).…”

Section: Coursementioning

confidence: 99%

Knee arthropathy secondary to Mycobacterium scrofulaceum.

Molony¹,

Connolly²

1973

Annals of the Rheumatic Diseases

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“…In an attempt to delay the development of resistance we combined 1314, 1 g., with tetracycline, 4 g., both in two divided *doses daily. Tetracycline was used because it has only very slight antituberculous activity but may delay the emergence of resistance to certain antituberculous drugs (Stewart et al, 1954;Murdoch and Stewart, 1956). We were therefore able to assess the antituberculous activity of 1314 more accurately than if it had been given in combination with a more effective drug.…”

Section: Meditjoh Preliminary Communicationsmentioning

confidence: 99%

Case of Twin Pregnancy in a Double Uterus

Kennedy¹

1959

BMJ

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The Use of Oxytetracycline in Preventing or Delaying Isoniazid Resistance in Pulmonary Tuberculosis

Cited by 21 publications

References 9 publications

The Effect of Isonicotinic Acid Hydrazide on the Oxidative Metabolism of Mycobacterium tuberculosis var. bovis B.C.G.

The Effect of Isonicotinic Acid Hydrazide on the Oxidative Metabolism of Mycobacterium tuberculosis var. bovis B.C.G.

Knee arthropathy secondary to Mycobacterium scrofulaceum.

Case of Twin Pregnancy in a Double Uterus

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