Development of Drug Resistance in MTB

Drug resistance in Mycobacterium tuberculosis occurs when there is acquisition of mutations in genes that code for anti-TB drug targets or drug-activating enzymes.

Drug resistance in Tuberculosis (TB) occurs through two main mechanisms shown in the figure below.

Figure: Mechanisms or Types of Drug Resistance in TB

The mechanism of transmission of drug-resistant (DR) and drug-sensitive (DS) TB is the same i.e., via infectious aerosols.

Acquired drug resistance is multi-factorial, and may be due to:​

• Lack of access to quality-assured anti-TB drugs for proper treatment
• Lack of adherence to the regimen or interrupted therapy which could be due to complex dosing strategies, serious adverse drug reactions and drug–drug interactions
• Inappropriate regimens
• Sub-therapeutic dosing
• Use of expired or substandard anti-TB drugs
• Malabsorption ​of oral anti-TB drugs which can be seen, for example, in HIV patients.

Resources

• Navisha Dookie et al. Evolution of Drug Resistance in Mycobacterium tuberculosis: A Review on the Molecular Determinants of Resistance and Implications for Personalized Care, Journal of Antimicrobial Chemotherapy, Volume 73, Issue 5, May 2018.
• Bento J, Duarte R, Brito MC, et al. Malabsorption of Antimycobacterial Drugs as a Cause of Treatment Failure in Tuberculosis, BMJ, September 2010.
• Biadglegne F, Sack U, Rodloff A. Multidrug-resistant Tuberculosis in Ethiopia: Efforts to Expand Diagnostic Services, Treatment and Care. Antimicrobial Resistance Infection Control, 2014.