Table 3.

Outline of possible explanations for anti-tuberculosis treatment failure

Types of reasons	Reason for treatment failure	Mechanisms	References
Host conditions	Body weight	Prescriptions without considering the body weight	[14, 15]
	Obesity	Impact on drug binding to albumin, increase in cytochrome P450 2E1 activity and phase II conjugation activity	[19]
	Special metabolism of the drug	Hepatic N-acetyltransferase 2 (NAT2) genotype affects the INH acetylator status and activity	[23, 27, 28]
	Malabsorption	Gut permeability and solubility; hepatic and renal clearance	[29, 30, 132]
	Failure to reach in EPTB	Anatomic barriers to drug penetration	[7, 133, 134]
Bacterial changes	Physical barrier of the cell wall	Increased dosage of anti-TB drugs might enhance drug permeation across the thicker cell wall into the bacilli	[40, 41]
		Formation of infectious biofilms	[43, 47, 48, 135]
	Drug efflux pumps	Efflux pumps are the first step in a general pathway to drug resistance	[58–61]
	Metabolic state of M. tuberculosis	Metabolic shutdown renders M. tuberculosis tolerant to a number of antibiotics	[62, 63]
	Special genotyping clinical isolates	Manu2 found to be significantly associated with mixed infections, resulting in hetero-resistance	[64, 65]