Forty
isoniazid-resistant Mycobacterium tuberculosis isolates were characterized on the basis of phenotypic properties (i.e.,
catalase activity, MIC of
isoniazid, and growth pattern in the presence of 7 different concentrations of
isoniazid) and alterations in the katG gene (
codons 315 and 463). Three different growth patterns could be distinguished: concentration-dependent inhibition of growth was observed in 29 strains, similar growth at all concentrations was seen in 7 strains, and enhanced growth at low concentrations of
isoniazid was evident in 4 strains. The MIC of
isoniazid was < or = microg/ml for 29 of 40 strains. Mutation at
codon 315 of the katG was detected in 28 of 40 strains. However, only one of the seven strains for which the MIC of
isoniazid was > or = 16 microg/ml had mutation at this
codon. Five of these seven strains for which the MIC was > or = 16 microg/ml had no
catalase activity. The results indicate that the MIC of
isoniazid for a majority of strains is below the level achievable in serum. Therefore,
isoniazid may be beneficial for the treatment of some cases of
multidrug-resistant tuberculosis. Determination of
catalase activity
aids in the detection of isolates for which MICs are high and could, in conjunction with molecular methods, provide rapid detection of most
isoniazid-resistant strains.