Isoniazid restance in the tubercle bacillus remains a matter of moment to the public
health, so researches in the behavior of the affected organism concern all who deal with
the prevention and care of the still most important communicable disease in Korea.
Although many a study disclosed the mystery and potential threat of drug resistance of
Isoniazid, still conflicting evidence has accumulated I the literature concerning the
significance of INH-resistant tubercle bacilli.
Several reported studies have shown that isoniazid-resistant mutants of tubercle bacilli
may not be fully pathogenic for guinea pigs, though these retain all or nearly all of
their pathogenicity for white mice(Middlebrook, Morse, 1954). Middlebrook also has
shown that isoniazid-resistant mutants of tubercle bacilli recovered in vitro are deficient
in endogenous catalase actvity and thant it is possible to isolate isoniaxid-resistant
mtuants which differ in their magnitude of catalase activity. Therefore there is
considerable evidence that tubercle bacilli which are highly restant to isoniazid have
diminution or even vitrual loss of pathogenicity for guinea pigs. a property hitherto
considered virtualy synonymous with pathogenicity for humans (Cohn. Peizer, 1953).
Were these highly resistant strains to prove of diminished virulence for humans, it
would obviously desirable to attempt to achieve in patients a state of high ressitance.
However the state of high resistance has been reported to be fluctuate in vitro and in
vivo and concerning this feature, the available evidence are still contradictory.
When isoniazid resistant tubercle bacilli are demonstrated in patients with pulmonary
tuberculosis, these populations of bacilli usually prove to consist of a mixture of highly
resistant, catalase negative, low-virulent bacilli and of slightly resistant, catalase
positive, high virulent bacilli, and frequently also of bacilli which are still highly senstive
to isoniazid. On the one hand, there is an increasing tendency to explain above
mentioned fluctuation as a matter of their population composition, while on the other
hand, there are many insisting of their permanency of resistance.
Thus, the problems concerning INH-resistant bacilli are still complicated and
unelucidated and call for further investigations.
In this artcle, author intended to pursue the variation of degrees of resistance in mice
and by serial repeate animal passage. In the first experiment, isoniazid-resistant strain
of boving Ravenel was incoulated into mice and was re-cultured at various intervals
from the organs of the animals. The re-cultured strain was examined for resistance.
In the second experiment, the same strain from lungs of previous experiment was
repeatedly inoculated into the tail veins of exterimental mice groups after the same
checking procedures.
Followings are the obtained results:
1. The re-culturability was best observed in the lung compared with the liver and the
spleen.
2. Even in the complete resistant strain of INH 100γ/㎖, the variation of degrees of
resistance was observed by single and serial passage.
i. The time lapse seemed to cause the gradual decrease in its degrees of resistance.
ii. The fluctuation of resistance was apparently noted in the lung compared with the
liver and spleen.
3. There was no apparent tendency to be replaced by the low grade mutants or
sensitive tubercle bacilli even by serial animal passage.
4. In a series of tubes of solid culture medium containing graded concentrations of
INH, no colonies were able to be seen in the media containing more than 1γ/㎖ of INH
as of 20 reading day in the single animal passage experiment, while colonies were
observed in the all tubes of various concentrations of INH in the serial animal passage
experiment.
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