Resistance to drugs in tuberculosis develops by the following mechanism:

Strains of M. tuberculosis resistant to individual drugs arise by spontaneous point mutations in the mycobacterial genome that occur at low but predictable rates (10-7-10-10 for the key drugs). The development of drug-resistant TB is invariably the result of monotherapy. Drug-resistant TB may be either primary or acquired. Primary drug resistance is that which develops in a strain infecting a patient who has not previously been treated. Acquired resistance develops during treatment with an inappropriate regimen. Ref: Raviglione M.C., O'Brien R.J. (2012). Chapter 165. Tuberculosis. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison's Principles of Internal Medicine, 18e.