Studies on Effects of Ethionamide on Tubercle Bacilli Resistant to Several Antituberculosis Drugs as well as of the Latter Drugs on the Ethionamide Resistant Tubercle Bacilli.
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The effect of ethio namide on the tubercle bacilli resistant to major antituberculosis drugs and of the other drugs on the ethionamide resistant bacilli were examined by following changes of the rates of resistant populations in the strains.<BR>Six strains were used which had been isolated from the patients administered with antituberculosis drugs previously. Those strains were proved as partially resistant to one or more of isoniazid, streptomycin and PAS. Also the ethionamide resistant variant of H37Rv, strain was used which had been obtained by serial cultivations in liquid media containing ethionamide.<BR>Dubos' media without and with O.5γ of ethionamide per ml or other antituberculosis drugs in the subinhibitory concentrations were inoculated w: th these strains and incubated at 37°C for a week. Before and after four to ten transfers every seventh day, the rates of drug resistant populations of each strain were examined by the cultivation on Ogawa's egg media containing different concentrations of the appropriate drugs.<BR>The effect of ethionamide on population of the strains resistant to other antituberculosis drugs was as follows:<BR>1) The rates of the high grade drug resistant individuals in the isoniazid resistant strains evidently decreased after the 4th and the 8th transfers in liquid media containing 0.5γ of ethionamide per ml.<BR>2) The difference between decreases of the strept omycin resistant populations by the transfers in media containing no drug and of those containing ethionamide was significant.<BR>3) The same result as above was obtained with PAS resistant strains.<BR>4) With the double resistant strain to streptomycin and isoniazid, the decrease of resistant population was detected at the same rate after the transfers both in media with and without ethionamide. The effects of antituberculosis drugs on ethionamide resistant strain were as follows:<BR>1) The rate of bacterial population of the ethionamide resistant strain was unchanged even after eight transfers in media containing no drug and containing the appropriate drugs at concentrations of O.01γ of isoniazid per ml, of O.5γ of streptomycin per ml, of O.1γ of PAS per ml, of O.5γ of kanamycin per ml, of 250γ of pyrazinamide per ml and of 2.5γ of cycloseline per ml.<BR>2) With the mixed strain which was composed of ethionamide resistant variant and original sensitive strain of H37Rv in a ratio of three to seven, the complete loss of the populations resistant to 50γ/ml and 100γ/ml of ethionamide was observed a fter four transfers even in the media without drugs.<BR>In summary, the populations resistant to isoniazid, streptomycin or PAS in the strains of tubercle bacilli were more susceptible to ethionamide than the sensitive ones.<BR>The difference of susceptibility to the above various antituberculosis drugs was not significant between the ethionamide resistant and the ethionamide sensitive populations.
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