Bedaquiline (trade name Sirturo, code names TMC207 and R207910) is a diarylquinoline anti-tuberculosis drug, which was discovered by a team led by Koen Andries at Janssen Pharmaceutica. When it was approved by the FDA on the 28th December 2012, it was the first new medicine to fight TB in more than forty years, and is specifically approved to treat multi-drug-resistant tuberculosis. Bedaquiline is a diarylquinoline antimycobacterial drug that inhibits the proton pump of mycobacterial ATP (adenosine 5'-triphosphate) synthase, an enzyme that is essential for the generation of energy in Mycobacterium tuberculosis. Bacterial death occurs as a result of bedaquiline.

PRIFTIN® (rifapentine) is indicated in adults and children 12 years and older for the treatment of active pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis. PRIFTIN must always be used in combination with one or more antituberculosis (anti-TB) drugs to which the isolate is susceptible. Rifapentine 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. And it acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death. 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. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifampin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency. Rifapentine has shown higher bacteriostatic and bactericidal activities especially against intracellular bacteria growing in human monocyte-derived macrophages.

Rifabutin 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 prophylaxis of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection. Multiple dosing of rifabutin has been associated with induction of hepatic metabolic enzymes of the CYP3A subfamily. Rifabutin’s predominant metabolite (25-desacetyl rifabutin: LM565), may also contribute to this effect. Similarly, concomitant medications that competitively inhibit the CYP3A activity may increase plasma concentrations of rifabutin. Common adverse reactions include discoloration of skin, rash, diarrhea, disorder of taste, indigestion, loss of appetite, nausea, vomiting, increased liver aminotransferase level (mild), ocular discoloration, uveitis, abnormal color of body fluid.

Ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid) is the synthetic antimicrobial agent for oral or intravenous administration. Ciprofloxacin is a member of the fluoroquinolone class of antibacterial agents. The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination. Ciprofloxacin is used to treat a wide variety of infections, including infections of bones and joints, endocarditis, gastroenteritis, malignant otitis externa, respiratory tract infections, cellulitis, urinary tract infections, prostatitis, anthrax, and chancroid. In the United States, ciprofloxacin is pregnancy category C. This category includes drugs for which no adequate and well-controlled studies in human pregnancy exist, and for which animal studies have suggested the potential for harm to the fetus, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Fluoroquinolones have been reported as present in a mother's milk and thus passed on to the nursing child. Oral and intravenous ciprofloxacin is approved by the FDA for use in children for only two indications due to the risk of permanent injury to the musculoskeletal system: Inhalational anthrax (postexposure) and Complicated urinary tract infections and pyelonephritis due to Escherichia coli.

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.

ETHAMBUTOL HYDROCHLORIDE is an oral chemotherapeutic agent which is specifically effective against actively growing microorganisms of the genus Mycobacterium, including M. tuberculosis. Ethambutol inhibits RNA synthesis and decreases tubercle bacilli replication. Nearly all strains of M. tuberculosis and M. kansasii as well as a number of strains of MAC are sensitive to ethambutol. Ethambutol inhibits arabinosyl transferases which is involved in cell wall biosynthesis. By inhibiting this enzyme, the bacterial cell wall complex production is inhibited. This leads to an increase in cell wall permeability. ETHAMBUTOL HCl is indicated for the treatment of pulmonary tuberculosis. It should not be used as the sole antituberculous drug, but should be used in conjunction with at least one other antituberculous drug.

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

Isoniazid is a bactericidal agent active against organisms of the genus Mycobacterium, specifically M. tuberculosis, M. bovis and M. kansasii. Isoniazid is recommended for all forms of tuberculosis in which organisms are susceptible. Isoniazid is a prodrug and must be activated by bacterial catalase. Isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. The most frequent adverse reactions to isoniazid are those affecting the nervous system and the liver.

4-AMINOSALICYLIC ACID (Paser) is an anti-tuberculosis drug used to treat tuberculosis in combination with other active agents. 4-AMINOSALICYLIC ACID (Paser) is most commonly used in patients with Multi-drug Resistant TB (MDR-TB) or when isoniazid and rifampin use is not possible due to a combination of resistance and/or intolerance. There are two mechanisms responsible for aminosalicylic acid's bacteriostatic action against Mycobacterium tuberculosis. Firstly, aminosalicylic acid inhibits folic acid synthesis (without potentiation with antifolic compounds). The binding of para-aminobenzoic acid to pteridine synthetase acts as the first step in the folic acid synthesis. Aminosalicylic acid binds pteridine synthetase with greater affinity than para-aminobenzoic acid, effectively inhibiting the synthesis of folic acid. As bacteria are unable to use external sources of folic acid, cell growth and multiplication slow. Secondly, the aminosalicylic acid may inhibit the synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis.