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±w -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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