Characterization of isoniazid-resistant strains of Mycobacterium tuberculosis on the basis of phenotypic properties and mutations in katG

Forty isoniazid-resistant Mycobacterium tuberculosis isolates were characte rized on the basis of phenotypic properties (i.e,, catalase activity, MIC o f isoniazid, and growth pattern in the presence of 7 different concentratio ns of isoniazid) and alterations in the katG gene (codons 315 and 463), Thr ee different growth patterns could be distinguished: concentration-dependen t inhibition of growth was observed in 29 strains, similar growth at all co ncentrations was seen in 7 strains, and enhanced growth at low concentratio ns of isoniazid was evident in 4 strains. The MIC of isoniazid was less tha n or equal to4 mug/ml for 29 of 40 strains. Mutation at codon 315 of the ka tG was detected in 28 of 40 strains. However, only one of the seven strains for which the MIC of isoniazid was greater than or equal to 16 mug/ml had mutation at this codon. Five of these seven strains for which the MIC was g reater than or equal to 16 mug/ml had no catalase activity. The results ind icate that the MIC of isoniazid for a majority of strains is below the leve l achievable in serum. Therefore, isoniazid may be beneficial for the treat ment of some cases of multidrug-resistant tuberculosis. Determination of ca talase activity aids in the detection of isolates for which MICs are high a nd could, in conjunction with molecular methods, provide rapid detection of most isoniazid-resistant strains.