The Probable Mechanism of Streptomycin Action in Tuberculosis *

The mechanism of streptomycin action in tuberculosis still appears to be an open question. Although from the first suggestion of its use for treating tuberculous man, it was taken for granted that its action was simply that of a tuberculostatic agent in vivo, simulating the action noted in vitro in certain culture tests under definitely established conditions. There were a few enthusiasts who led one to infer that streptomycin could kill tubercle bacilli readily and directly in vivo5 as well as in vitro.7 Such simple action would certainly prove highly desirable in achieving a cure for tuberculosis, but unfortunately it takes into little account the multiple problems involved in the various reactions of the tubercle bacillus and the similarities upon which are based its parasitism in the human or animal body. These mechanisms are also far from being completely elucidated. Extreme caution is necessary to avoid hasty deductions, if past experiences with the tubercle bacillus and tuberculosis are used as evidence. In a preliminary report2 in 1946, it was pointed out that: Streptomycin properly administered and in proper dosage is capable of retarding the development or growth of human tubercle bacilli both in vitro... and in vivo. The concentration of streptomycin required to retard the growth of tubercle bacilli in vitro in good nutrient mediums can only be attained in vivo for a brief period by any route of administration or amount of streptomycin that can be used. There is no evidence available . . . to indicate that streptomycin enters the important organs in appreciable amount for any significant time, although it is present in the blood, or that it accumulates in these organs. There is no evidence that tubercle bacilli adsorb or absorb streptomycin or that it accumulates in these bacilli in vitro or in vivo. In 1947 it was further noted4 that: "Streptomycin cannot be considered a cure for tuberculosis in man at present since it is incapable of destroying virulent human tubercle bacilli or of completely retarding their development in vivo under the best experimental conditions. In experimental virulent infection, streptomycin is capable of retarding tuberculosis, but it is incapable of completely negating a lethal issue from such infection." Still later, it was recorded3 that "Streptomycin does