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.