Table 3 Outline of possible explanations for anti-tuberculosis treatment failure

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

[58,59,60,61]

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]