title: [Studies on the problems of resistance to antituberculous drugs. II--2. Clinically significant critical concentration of streptomycin, isoniazid, kanamycin and ethambutol].
abstract: The proportion method demands an exact count of the colonies on the control and drug-containing media to calculate an exact percentage of resistant bacilli among bacilli-population. To realize this objective, the bacilli suspension must be fresh and homogeneous, susceptible and resistant bacilli must be equally distributed, each bacillus must be dispersed as a single cell when the bacilli suspension is diluted, colony count must be reduced at a rate parallel to the dilution. The critical concentration of each drug should essentially be determined in a clinical manner, however as the multi-drug combination therapy in the rule for the treatment of tuberculosis, it is very difficult to make an exact determination of the resistance to each of drugs. It may be better, as Canetti pointed out, to decide using the pure bacteriological method and later compare findings with clinical studies, making changes in the future if so required. We choose to follow their criteria for nearly all of the drugs making only a few exceptions. 1) SM: DH-SM is not available in Japan as Japanese government prohibits its production. Growth on the medium containing SM (only concentration of less than 4 micrograms/ml) was more abundant than on DH-SM media. Not knowing the fact that when an air-tight cap was used on the medium tube, the result of susceptible test shows 4-10 times higher resistance, we first used an air permeable cork cap. Futamura noticed the fact later and devised the M-type cap, which is air-tight originally, but allows air to flow into the tube automatically when needed. But such cap seemed not necessarily to be expected when employed routinely in the case of a SM concentration of 4 micrograms/ml. Next for the clinical study, considering the combined triple-drug treatment and relapse rate of positive bacilli after six months and one year, we adopted an 1% SM solution (10 micrograms/ml) and the 0.2 microgram/ml of INH as the clinically significant criteria. 2) RFP: Among previously untreated patients, 1,346 were tested using only the indirect method, revealing a critical concentration at 10 micrograms/ml. Their critical proportions were 1-9% in 14 patients (1.0%) which might be technical mistakes, because retested 1/3 cases of them were found 0% to 10 micrograms/ml of RFP and the remaining 2/3 also must be 0%. For the detailed explanation, please see the literature (5). There were also 3 patients who critical proportion were 50% or more.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: National Nakano Chest Hospital, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Baba
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004977:Ethambutol / Q000494:pharmacology; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D007612:Kanamycin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013307:Streptomycin / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D007612:Kanamycin; D004977:Ethambutol; D007538:Isoniazid; D013307:Streptomycin