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Strains of M. tuberculosis resistant to individual drugs arise by spontaneous point mutations in the mycobacterial genome, which occur at low but predictable rates.

  • Isoniazid: 1 in every 106 cell divisions.
  • Rifampicin: 1 in every 109 cell divisions.
  • Streptomycin: 1 in every 106 cell divisions.
  • Ethambutol: 1 in every 105 cell divisions.
  • Pyrazinamide: 1 in every 105 cell divisions.

Because there is no cross-resistance among the commonly used first line anti-TB drugs, the probability that a strain will be resistant to two drugs is the product of the probabilities of resistance to each drug and thus is quite low.

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