Interventions for Tuberculosis Control and Elimination
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The frequency of spontaneous mutations that confer resistance varies for the different drugs. The observation that isoniazid-resistant mutants are found more frequently than rifampicin-resistant mutants is explained, at least partially, by the fact that different gene mutations in M. tuberculosis may lead to isoniazid resistance while virtually all resistance to rifampicin appears to be related to mutations in a single gene.
The frequency of clincially relevant mutations is somewhat higher than suggested from this work, it may occur at a frequency of 1 per 10 million for rifampicin, and in 1 per 1 million for isoniazid.