From: Treating tuberculosis with high doses of anti-TB drugs: mechanisms and outcomes
Types of reasons | Reason for treatment failure | Mechanisms | References |
---|---|---|---|
Host conditions | Body weight | Prescriptions without considering the body weight | |
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 | ||
Malabsorption | Gut permeability and solubility; hepatic and renal clearance | ||
Failure to reach in EPTB | Anatomic barriers to drug penetration | ||
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 | |
Formation of infectious biofilms | |||
Drug efflux pumps | Efflux pumps are the first step in a general pathway to drug resistance | ||
Metabolic state of M. tuberculosis | Metabolic shutdown renders M. tuberculosis tolerant to a number of antibiotics | ||
Special genotyping clinical isolates | Manu2 found to be significantly associated with mixed infections, resulting in hetero-resistance |