Antimycobacterial Drugs and Tuberculosis

A drug used to prevent tuberculosis (TB) infection in people who have been exposed to the bacteria. It is also used to treat latent TB, which is when the bacteria are present in the body but are not causing any symptoms.

A drug used to treat Mycobacterium avium complex (MAC) infections, a type of lung disease that is common in people with HIV. It is also used for the prophylaxis of TB.

A prodrug that is converted to pyrazinoic acid in the body, where it becomes active. Pyrazinamide is an important drug used in the short-course treatment of TB.

A drug used in combination with other anti-TB medications to treat TB. It works by inhibiting the synthesis of mycolic acid, a component of the mycobacterial cell wall.

A side effect of ethambutol that involves damage to the optic nerve. This can lead to loss of visual acuity and difficulty distinguishing between red and green colors.

The process of preventing a disease from developing in the first place.

An infection of the bone.

An infection of the lining of the heart, which can be caused by bacteria.

Mycobacteria are a group of bacteria that are naturally resistant to many antibiotics. They are characterized by their unique structure, being Gram-positive, non-motile, and rod-shaped.

Mycobacteria are intracellular pathogens, which means they live inside cells, specifically macrophages. This makes them difficult to target with drugs that cannot easily penetrate cells.

The response to antimycobacterial drugs is usually slow, meaning it can take months or even years of treatment to eliminate the bacteria.

Tuberculosis (TB) is a serious infectious disease caused by the bacteria Mycobacterium tuberculosis. It mainly affects the lungs, but can also spread to other parts of the body. It is transmitted through the air.

When Mycobacterium tuberculosis enters the lungs, it can lead to various outcomes: 1) Immediate clearance (being eliminated by the body's defenses), 2) Primary disease (rapid development of active infection), 3) Latent infection (hidden infection without symptoms), or 4) Reactivation disease (active infection re-emerging after a latent period).

Isoniazid (INH) is a drug that is bactericidal at higher concentrations and bacteriostatic at lower concentrations. It inhibits the synthesis of mycolic acid, a crucial component of the mycobacterial cell wall.

Ethambutol is a drug that is effective against both extracellular and intracellular Mycobacteria, meaning it can target the bacteria both inside and outside of cells.

Pyrazinamide is a drug that is mainly effective against Mycobacterium tuberculosis bacteria that are in a dormant or inactive state. It is often used in combination with other drugs to provide broader coverage.

Ethambutol inhibits the synthesis of arabinogalactan, a component of the mycobacterial cell wall. This disrupts the formation of the cell wall and prevents the bacteria from growing.

Ethambutol is primarily excreted by the kidneys. In patients with impaired kidney function, the dose of ethambutol may need to be adjusted.

At a dosage of 15 mg/kg/day or less, visual disturbances are very rarely reported. However, if the dosage is increased to 25 mg/kg/day, it is recommended to monitor visual acuity periodically.

Streptomycin is a member of the aminoglycoside class of antibiotics. It exhibits bactericidal activity against various mycobacteria, including TB, MAC, and Mycobacterium kansasii.

Streptomycin primarily targets extracellular tubercle bacilli. It has limited penetration into cells, meaning it's less effective against intracellular bacteria.

Streptomycin crosses the blood-brain barrier (BBB) and reaches therapeutic concentrations in the cerebrospinal fluid when the meninges are inflamed. This makes it effective for treating TB meningitis.

Streptomycin is often administered via IV or IM injection. It's typically used when an injectable drug is necessary.

Aminoglycosides, like streptomycin, can cause ototoxicity (damage to the inner ear) and nephrotoxicity (damage to the kidneys). These toxic effects are dose-dependent and more likely to occur with prolonged use.

A type of antibiotic that targets bacterial DNA replication, effectively treating both common and uncommon Mycobacteria infections.

A potent antibiotic that inhibits the synthesis of mycolic acids, essential components of mycobacterial cell walls, effectively targeting Mycobacteria.

A powerful antimycobacterial drug that inhibits bacterial RNA polymerase, leading to disruption of bacterial protein synthesis. It is effective against both common and uncommon Mycobacteria.

A newer anti-TB drug that directly targets ATP synthase, a crucial enzyme for energy production in bacteria, particularly Mycobacteria.

A novel antibiotic approved for treating multi-drug resistant TB, inhibiting synthesis of mycolic acids, essential components of the Mycobacterial cell wall.

An infectious disease caused by Mycobacterium leprae or Mycobacterium lepromatosis, affecting the skin, peripheral nerves, respiratory tract, and other tissues.

A front-line drug in leprosy treatment, interfering with bacterial folate synthesis, leading to their demise.

Isoniazid is activated by mycobacterial catalase-peroxidase (KatG) forming a covalent complex with an acyl carrier protein (AcpM) and a beta-ketoacyl carrier protein synthetase (KasA). This inhibits mycolic acid synthesis, essential for mycobacterial cell walls, leading to cell death.

Isoniazid is readily absorbed from the gastrointestinal tract, distributing to all body fluids and tissues, even penetrating caseous material and macrophages. This allows it to effectively target both intracellular and extracellular mycobacteria.

The typical dosage of Isoniazid is 5 mg/kg/day, with an adult dose of 300 mg once a day. Higher doses up to 10 mg/kg/day or 900 mg twice-weekly may be used for serious infections or malabsorption.

Isoniazid can cause side effects like optic neuritis, peripheral neuritis, allergic reactions (fever, rash, lupus), hepatitis (contraindicating further use), gastric upset, hemolytic anemia, and peripheral neuropathy.

Slow acetylators are individuals whose liver cannot efficiently detoxify reactive drug metabolites, leading to increased risk of adverse effects from Isoniazid. These individuals often require lower doses or additional monitoring.

Pyridoxine (vitamin B6) is recommended for those at risk of neuropathy, often at a dose of 25-50 mg per day. This supplementation can help prevent or reduce the development of nerve damage associated with Isoniazid use.

Rifampin is a bactericidal antibiotic that binds to the beta subunit of bacterial DNA-dependent RNA polymerase, effectively inhibiting RNA synthesis. This disruption in RNA production leads to the death of bacteria.

Rifampin is well absorbed orally and primarily excreted through the liver into the bile. It readily penetrates macrophages, allowing it to target both intracellular and extracellular bacteria.