The Virulence of Isoniazid Resistant Tubercle Bacilli, Recovered from Patients During Treatment

Abstract

1) Tubercle bacilli strains susceptible to isoniazid, streptomycin, para-aminosalicylic acid and conteben (5 strains, examined in 16 guinea pigs) produce in the guinea pig generalized tuberculosis of lymph nodes and internal organs. As an expression of the severity of tuberculosis is to be observed a high macroscopic (10-16) and a high cultural (6-7) tuberculous index at an average survival time of two to three months. These indices mean the sum of the macroscopic numbers for the different organs and the sum of the organs with positive cultures. 2) Strains resistant to isoniazid, recovered from patients during treatment with isoniazid (21 strains examined in 56 guinea pigs) produced at the examination of the first egg medium subculture with a medium dose of infection (0.01 mg.) and in the same period only minimal tuberculosis of lymph nodes and practically no tuberculosis in the organs and, corresponding to this finding, only a small number of positive organ cultures. At the highest degree of virulence attenuation, which is combined with a distinct attenuation of growth on egg medium, there were observed macroscopic and cultural indices of 1.6 and 1.9. 3) The attenuation of virulence decreases somewhat, changing from the moderately dysgonic resistant strains via the eugonic resistant ones to the moderately susceptible eugonic strains, but their indices (the latter have such of 5.3 and 4.3) are distinctly much lower than those of our susceptible strains. 4) To demonstrate the attenuation of virulence it must be supposed, that only strains were examined, which contain without exception resistant mycobacteria, but not susceptible or more susceptible ones. 5) If guinea pigs are infected with cultures containing mixtures of resistant and susceptible mycobacteria or with artificial mixtures of susceptible and resistant single colony cultures, the susceptible organisms spread (generalize) more rapidly than the resistant ones of the same population. 6) Experiments with single colony cultures indicate that the single bacterium does not lose its resistance in the guinea pig, at least not in the first animal passage. The cause of the more rapid generalization may be the more rapid multiplication of susceptible bacteria in contrast to the resistant ones of the same population in the animal.