Tuberculosis Drugs and Mechanisms of Action

First-Line Treatment of TB for Drug-Sensitive TB

Isoniazid, Rifampin, Ethambutol and Pyrazinamide are the first-line of treatment of drug-sensitive TB.
Credit: NIAID

Several new types of TB drugs currently under development are shown here. NIAID has supported the development of five of these compounds, SQ-109, PA-824 (Pretomanid)​, Sutezolid, Linezolid, and Meropenem, which are denoted by asterisks (*) above.


Tuberculosis, which results from an infection with Mycobacterium tuberculosis, can be cured with a combination of first-line drugs taken daily for several months. 

Multidrug-Resistant Tuberculosis (MDR TB) and Second-Line Treatments

Thioamides, Diarylquinoline, Cyclic Peptides, Nitroimidazole, Ethambutol, Pyrazinamide, Aminoglycosides, Cycloserine, Fluoroquinolones, and Para-aminosolicylic acid are second-line treatments. Isoniazid and Rifampin are bacteria resistant.
Credit: NIAID

MDR TB occurs when a Mycobacterium tuberculosis strain is resistant to isoniazid and rifampin, two of the most powerful first-line drugs. To cure MDR TB, healthcare providers must turn to a combination of second-line drugs, several of which are shown here. Second-line drugs may have more side effects, the treatment may last much longer, and the cost may be up to 100 times more than first-line therapy. MDR TB strains can also grow resistant to second-line drugs, further complicating treatment.

Extensively Drug-Resistant Tuberculosis (XDR TB) - Options for Treatment

Bedaquiline and Delamanid are new drugs. Ethambutol, Pyrazinamide, Thioamides, Cycloserine, Para-aminosalicylic acid, Streptomycin, and Clofazimine are possibly effective. Kanamycin, Capreomycin and Amikacin are injectable second-line.
Credit: NIAID

Bedaquiline and Delamanid are new drugs. Ethambutol, Pyrazinamide, Thioamides, Cycloserine, Para-aminosalicylic acid, Streptomycin, and Clofazimine are possibly effective. Kanamycin, Capreomycin and Amikacin are injectable second-line.


XDR TB occurs when a Mycobacterium tuberculosis strain is resistant to isoniazid and rifampin, two of the most powerful first-line drugs, as well as key drugs of the second line regimen—any fluoroquinolone and at least one of the three injectable drugs shown above. XDR TB strains may also be resistant to additional drugs, greatly complicating therapy.

New Candidate TB Drugs Under Development

SQ-109, Meropenem, Q203, PBTZ169, BTZ043, PA-824, Macrolides, Rifapentine, Sutezolid, and Linezolid are new candidate TB drugs under development.
Credit: NIAID

Several new types of TB drugs currently under development are shown here. NIAID has supported the development of five of these compounds, SQ-109, PA-824 (Pretomanid)​, Sutezolid, Linezolid, and Meropenem, which are denoted by asterisks (*) above.

 

Mechanisms of Action of Current TB Drugs

Thiomaides, Nitroimidazoles, Ethambutol, and Cycloserine act on cell wall synthesis. Diarylquinoline inhibits ATP synthase. PAS, Fluoroquinolones, Cyclic Peptides and Aminoglycosides act on the DNA.
Credit: NIAID

Thiomaides, Nitroimidazoles, Ethambutol, and Cycloserine act on cell wall synthesis. Diarylquinoline inhibits ATP synthase. PAS, Fluoroquinolones, Cyclic Peptides and Aminoglycosides act on the DNA.


Tuberculosis drugs target various aspects of Mycobacterium tuberculosis biology, including inhibition of cell wall synthesis, protein synthesis, or nucleic acid synthesis. For some drugs, the mechanisms of action have not been fully identified.

Mechanisms of Action of TB Drugs Under Development

Nitroimidazoles, SQ-109,, Meropenem, and Benzothiazinones act on cell wall synthesis. Imidazopyridine Amide inhibits ATP synthesis. Rifamycins, Oxazolidinones and Macrolides act on DNA.
Credit: NIAID

Nitroimidazoles, SQ-109,, Meropenem, and Benzothiazinones act on cell wall synthesis. Imidazopyridine Amide inhibits ATP synthesis. Rifamycins, Oxazolidinones and Macrolides act on DNA.


Tuberculosis drugs target various aspects of Mycobacterium tuberculosis biology, including inhibition of cell wall synthesis, protein synthesis, or nucleic acid synthesis. For some drugs, the mechanisms of action have not been fully identified.

About the Illustrations

The photo of Mycobacterium tuberculosis is from the Centers for Disease Control and Prevention, CDC/Dr. Ray Butler, Janice Carr. This illustration is in the public domain. Please credit the National Institute of Allergy and Infectious Diseases (NIAID).

Additional TB Information

Content last reviewed on April 19, 2016