THE EFFECT OF SULFATHIAZOLE IN DELAYING THE EMERGENCE OF ISONIAZID RESISTANCE IN TUBERCULOUS PATIENTS

Abstract

In 1953 it has been reported by KIMINO, ABO and KATSUNUMA that a marked clinical improveme nt of pulmonary tuberculosis has been produced by the combined use of isoniazid plus sulfathiazole. Concomitantly with this report, KimINO reported the in vitro effect of sulfathiazole in delaying the emergence of isoniazid resistance in Mycobacterium avium, and then TSUICAMURA, SUZUKI and KIMINO reported that the effect was produced not only by sulfathiasole but also another sulfonamide drugs(sulfisoxazole, sulfamerazine, sulfadimezine, etc.), and studied the mechanism of sulfonamides in delaying the in vitro emergence of isoniazid resistance in M. avium. It has been also found by TSUKAMURA that, among sulfonamides, sulfathiazole and sulfisoxazole inhibit most effectively the growth of Mycobacterium tuberculosis and Mycobacterium avium on an egg medium as well as on a synthetic medium. Independently of our stud i es, NAIT0 and SAITO and his associates have reported that the combined use of isoniazid plus sulfisoxazole, which is less toxic to human bodies than sulfathiazole, has given a very marked therapeutic effect on patients with pulmonary tuberculosis, and their results have been supported by USHIBA and his associates. The effect of sulfisoxazole in delaying the in vivo emergence of isoniazid resistance is not yet certainly demonstrated. Therefore, it is the purpose of the present paper to demonstrate the effect of sulfathiazole in delaying the emergence of isoniazid resistance in tubercle bacilli of patients.