Second line
The second line drugs (WHO groups 2, 3 and 4) are only used to treat disease that is resistant to first line therapy (i.e., for extensively drug-resistant tuberculosis (XDR-TB) or multidrug-resistant tuberculosis (MDR-TB)). A drug may be classed as second-line instead of first-line for one of three possible reasons: it may be less effective than the first-line drugs (e.g., p-aminosalicylic acid); or, it may have toxic side-effects (e.g., cycloserine); or it may be effective, but unavailable in many developing countries (e.g., fluoroquinolones):
aminoglycosides (WHO group 2): e.g., amikacin (AMK), kanamycin (KM);
polypeptides (WHO group 2): e.g., capreomycin, viomycin, enviomycin;
fluoroquinolones (WHO group 3): e.g., ciprofloxacin (CIP), levofloxacin, moxifloxacin (MXF);
thioamides (WHO group 4): e.g. ethionamide, prothionamide
cycloserine (WHO group 4)
terizidone (WHO group 5)

Third line
Third-line drugs (WHO group 5) include drugs that may be useful, but have doubtful or unproven efficacy:
rifabutin
macrolides: e.g., clarithromycin (CLR);
linezolid (LZD);
thioacetazone (T);
thioridazine;
arginine;
vitamin D;
bedaquiline.These drugs are listed here either because they are not very effective (e.g., clarithromycin) or because their efficacy has not been proven (e.g., linezolid, R207910). Rifabutin is effective, but is not included on the WHO list because for most developing countries, it is impractically expensive. Standard regimen
Rationale and evidence
Tuberculosis has been treated with combination therapy for over fifty years. Drugs are not used singly (except in latent TB or chemoprophylaxis), and regimens that use only single drugs result in the rapid development of resistance and treatment failure. The rationale for using multiple drugs to treat TB are based on simple probability.
DOTS is used with intermittent dosing (thrice weekly or 2HREZ/4HR3). Twice weekly dosing is effective but not recommended by the World Health Organization (WHO), because there is no margin for error (accidentally omitting one dose per week results in once weekly dosing, which is ineffective).Treatment with properly implemented DOTS has a success rate exceeding 95% and prevents the emergence of further multi-drug resistant strains of tuberculosis. Administering DOTS, decreases the possibilities of tuberculosis from recurring, resulting in a reduction in unsuccessful treatments. This is in part due to the fact that areas without the DOTS strategy generally provide lower standards of care. Areas with DOTS administration help lower the number of patients seeking help from other facilities where they are treated with unknown treatments resulting in unknown outcomes. However, if the DOTS program is not implemented or done so incorrectly positive results will be unlikely. For the program to work efficiently and accurately health providers must be fully engaged, links must be built between public and private practitioners, health services must be available to all, and global support is provided to countries trying to reach their TB prevention, and treatment aims. Some researchers suggest that, because the DOTS framework has been so successful in the treatment of tuberculosis in sub-Saharan Africa, DOTS should be expanded to non-communicable diseases such as diabetes mellitus, hypertension, and epilepsy. DOTS-Plus strategy
The WHO extended the DOTS programme in 1998 to include the treatment of MDR-TB (called "DOTS-Plus").