A Trial of the Combined Use of Antituberculous Agents Including Simultaneous Administration of Kanamycin and Streptomycin

Abstract

Both streptomycin and kanamycin are toxic to auditory organ. It was reported that hearing loss developed in some patients who received daily doses of 1g of kanamycin^1,2) and also that administration of 4g kanamycin per week could be administered with a very low rate of damage of the cranial eighth nerve and with an efficacy similar to that of 2g streptomycin per week¹⁾.

In vitro studies made by the author and his associates^3–5)> have shown that kanamycin represents an additive effect with streptomycin. It has been also found that kanamycin-resistant tubercle bacilli are several times more resistant to streptomycin and streptomycin resistant tubercle bacilli are as sensitive to kanamycin as sensitive cells previously not exposed to any drug. However, this one-way partial cross-resistance does not hinder the combined use of kanamycin and streptomycin, which has resulted a more bacteriostatic effect than anyone of these drugs alone. The combined use of these two drugs, kanamycin and streptomycin, appeared to be promising for the clinical purpose, if these two drugs had not an additive damage-effect on the auditory organ (dissociation between the damaging combined effect and the bacteriostatic combined effect). Thus, the combined use of kanamycin and streptomycin, with other antituberculous drugs, has been promoted by the author and preliminary studies^6,7) have shown that kanamycin and streptomycin may be administered simultaneously without any significant side effect. It has been suggested that kanamycin may attack a different point of the auditory organ from the attack point of streptomycin. These results appeared to warrant further trial. It is the purpose of the present paper to describe some data of this trial.