Rifampin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. It is FDA approved for the treatment of tuberculosis, meningococcal carrier state. Healthy subjects who received rifampin 600 mg once daily concomitantly with saquinavir 1000 mg/ritonavir 100 mg twice daily (ritonavir-boosted saquinavir) developed severe hepatocellular toxicity. Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. Common adverse reactions include heartburn, epigastric distress, anorexia, nausea, vomiting, jaundice, flatulence, cramps.

Cycloserine was discovered simultaneously in 1954 by Eli Lilly and Merck. The drug was approved for the treatment of active pulmonary and extrapulmonary tuberculosis and marketed under the name Seromycin (among the others). Cycloserine suppresses the synthesis of bacterial wall by inhibitin two enzymes: alanine racemase and d-alanine ligase.

Pyrazinamide is indicated for the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents. (The current recommendation of the CDC for drug-susceptible disease is to use a six-month regimen for initial treatment of active tuberculosis, consisting of isoniazid, rifampin and pyrazinamide given for 2 months, followed by isoniazid and rifampin for 4 months. Pyrazinamide should only be used in conjunction with other effective antituberculous agents. Pyrazinamide diffuses into M. tuberculosis, where the enzyme pyrazinamidase converts pyrazinamide to the active form pyrazinoic acid. Under acidic conditions, the pyrazinoic acid that slowly leaks out converts to the protonated conjugate acid, which is thought to diffuse easily back into the bacilli and accumulate. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids. However, this theory was thought to have been discounted. However, further studies reproduced the results of FAS I inhibition as the putative mechanism first in whole cell assay of replicating M. tuberculosis bacilli which have shown that pyrazinoic acid and its ester inhibit the synthesis of fatty acids . This study was followed by in vitro assay of tuberculous FAS I enzyme that tested the activity with pyrazinamide, pyrazinoic acid and several classes of pyrazinamide analogs. Pyrazinamide and its analogs inhibited the activity of purified FAS I. It has also been suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. Pyrazinoic acid has also been shown to bind to the ribosomal protein S1 (RpsA) and inhibit trans-translation. This may explain the ability of the drug to kill dormant mycobacteria

Streptomycin is a water-soluble aminoglycoside derived from Streptomyces griseus. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses. Aminoglycosides like Streptomycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically Streptomycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes. Streptomycin is indicated for the treatment of tuberculosis. May also be used in combination with other drugs to treat tularemia (Francisella tularensis), plague (Yersia pestis), severe M. avium complex, brucellosis, and enterococcal endocarditis (e.g. E. faecalis, E. faecium).

Clofazimine (Lamprene®) is a fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine (Lamprene®) exerts a slow bactericidal effect on Mycobacterium leprae (Hansen’s bacillus). It inhibits mycobacterial growth and binds preferentially to mycobacterial DNA. It also exerts anti-inflammatory properties in controlling erythema nodosum leprosum reactions. However, its precise mechanisms of action are unknown.

Glucosulfone (Glucosulfone Free Acid, or Promin) is a compound used to treat mycobacterial infections, such as tuberculosis and leprosy. It is converted to dapsone in the body, which also has been shown to have therapeutic effects against dermatitis herpetiformis, actinomycotic mycetoma, asthma, malaria, rheumatoid arthritis, Kaposiís sarcoma, pneumocystis carinii (pneumonia), subcorneal pustular dermatosis and cystic acne. Once converted to dapsone, it has haemotoxic effects (destroying red blood cells, or disrupting blood clotting, potentially causing organ or tissue damage).

Amithiozone, also known as thioacetazone, is an oral antibiotic, which is used in the treatment of tuberculosis. In 1991, the World Health Organization (WHO) recommended replacing thioacetazone with ethambutol in patients with known or suspected HIV infection. Thioacetazone is no longer included in WHO’s recommended first-line treatment for tuberculosis and is now reserved for uncommon situations in which treatment options have been compromised by resistance to other anti-tuberculosis medicines in HIV-negative individuals. Despite the increased recognition of this risk, thioacetazone remained in use mainly in low-income countries because of its low cost. Amithiozone has also been used in trials studying the treatment of Mycobacterium Avium-intracellular Infection. One of the possible mechanism action of the drug is interference with the metabolism of methionine of susceptible tubercle bacilli, which utilize methionine for nucleic acid synthesis.

Methaniazide (metaniazide) is the methanesulfonate derivative of isoniazid with antibacterial properties. It is used used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.

Isoniazid pyruvate is a metabolite of isoniazid. Isoniazid (Laniazid, Nydrazid), also known as isonicotinylhydrazine (INH), is an organic compound that is the first-line medication in prevention and treatment of tuberculosis. It has been claimed that isoniazone pyruvate causes less excretion of pyridoxine than isoniazid and might therefore be less likely to cause peripheral neuritis.